Nicotine DependenceNCT01511614

Nicotine Withdrawal Symptoms and Smoking Relapse

A study testing Transcranial Direct Current Stimulation, Nicotine patch and Varenicline Pill in people with Nicotine Dependence, run by National Institute on Drug Abuse (NIDA) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Background: Smoking is thought to cause changes in the brain that lead to addiction and craving. Smokers who try to quit experience nicotine withdrawal symptoms that include irritability, anxiety, and difficulty concentrating. These symptoms make it difficult for people to stop smoking. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Nicotine Dependence
What is being tested?: Transcranial Direct Current Stimulation, Nicotine patch and Varenicline Pill
Type of treatment: Pill or oral medicine, Medical device, Lifestyle or therapy programme
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 112 participants
Where: 1 siteUnited States
Study dates: 20 May 2013to 30 Mar 2020
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

All Subjects must:
Be between the ages of 18-65.
Be right-handed. Assessment tool(s): Edinburgh Handedness Inventory.
Be in good health. Justification: Many illnesses may alter fMRI signals as well as cognitive processes and neural functioning. Assessment tool(s): Participants will provide a brief health history during phone screening, and undergo a medical history and physical examination with a qualified IRP clinician.
Be free of current moderate to severe DSM-V Substance Use Disorder on any drug, except nicotine in smokers. Those with past moderate to severe use disorder on substances may be included, provided they are in sustained remission (and not on maintenance therapy for opioid use disorder) and are not intoxicated on the day of the imaging session. Justification: Moderate to severe use disorder on other substances may result in unique CNS deficits that could confound results and introduce excessive variance, while mild substance use disorder and substance use disorder in remission are common in community samples of smokers. Assessment tool(s): Computerized SCID or comparable assessment and DSM-5 substance use disorder assessment.
Be able to abstain from alcohol and other recreational drugs for 24 hours before each imaging session, and able to moderate caffeine intake 12 hours before each imaging session. Justification: Recent substance use, including alcohol, and caffeine modulate neural functioning in a way that would complicate data interpretation. Assessment tool(s): Self-report, breathalyzer, and urine toxicology screen with follow up neuromotor assessment to ensure absence of acute impairment with positive urine test.

Show all 11Show fewer

Smokers must meet the additional criteria:
Have a urine cotinine level corresponding to smoker status for the specific test being used, typically corresponding to a urine cotinine above about 200 ng/ml, and have been smoking for at least 1 year. Justification: The present protocol is interested in neurobiological mechanisms that underlie nicotine withdrawal, and is thus contingent on the presence of nicotine dependence. Assessment tool(s): Selfreport, commercial urine cotinine test corresponding to smoker status for the specific test being used, typically corresponding to a urine cotinine above about 200 ng/ml.
Be able to abstain from smoking for 12 hours prior to MRI-tDCS study sessions. Justification: The present protocol will investigate the effect of acute nicotine withdrawal on cognitive processes and response to tDCS. Assessment: Self-report and expired CO levels
In addition, non-smokers must meet:
Not have a history of daily cigarette smoking or have used any nicotine products continuously lasting more than a month, and no smoking or continuous use of any nicotine products within the past year. Assessment Tools: Self-report, urine cotinine test, and expired CO levels.

Who cannot join

All participants will be excluded if they:
Are not suitable to undergo an fMRI experiment due to certain implanted devices (cardiac pacemaker or neurostimulator, some artificial joints, metal pins, surgical clips or other implanted metal parts), body morphology, or claustrophobia. Justification: MR scanning is one of the primary measurement tools used in the protocol. Assessment tool(s): Prospective participants will fill out an MRI screening questionnaire and undergo an interview with an MR technologist. Questions concerning suitability for scanning will be referred to the MR Medical Safety Officer. Prospective participants will be questioned about symptoms of claustrophobia and placed in the mock scanner during their first visit to assess for possible difficulty tolerating the confinement of the scanner and for ability to fit into the scanner.
Have musculoskeletal abnormalities restricting an individual s ability to lie flat for extended periods of time. Justification: MR scanning sessions require participants to lie flat on their backs and remain perfectly still for approximately one hour. Therefore, conditions that would make that difficult (e.g. chronic back pain, significant scoliosis) will be exclusionary. Assessment tool(s): History and physical examination by a qualified IRP clinician, supplemented with a trial of lying in the mock scanner to assess comfort issues.
Have HIV or Syphilis. Justification: HIV and Syphilis both can have central nervous system (CNS) sequelae, thus introducing unnecessary variability into the data. Assessment tool(s): Oral HIV followed by blood test if oral test is + and STS+ without adequate prior treatment
Regularly or intermittently use any prescription (e.g., benzodiazepines, barbiturates), over-the-counter (e.g., cold medicine) medications that are likely to alter BOLD signal (neuronal-vascular coupling). Justification: The use of these substances may alter the fMRI signal and/or neural functions of interest in the current study. Assessment tool(s): History and comprehensive urine drug screening to detect benzodiazepines, antipsychotics, anticonvulsants, and barbiturates. Note: If a participant is intermittently taking a medication likely to affect BOLD signal, the participant may be excluded or if scanned, will be scanned in the same medication state for data continuity purposes (i.e. either all scan days are scheduled after 5 half-lives since last medication use; or all scan days are scheduled on medication).
Have any current neurological illnesses including, but not limited to, seizure disorders, frequent migraines or on prophylaxis, multiple sclerosis, cerebrovascular accident, movement disorders (except essential tremor, so long as it would not interfere with study tasks such as button pressing), history of significant head trauma, or CNS tumor. Justification: Neurological diseases alter CNS function and, possibly, the neuronal-vascular coupling that forms the basis of the fMRI signal. Assessment tool(s): History and physical examination by a qualified IRP clinician, urine drug screening for anticonvulsants not disclosed by history. History of head trauma with loss of consciousness of more than 30 minutes or with post-concussive sequelae lasting more than two days, regardless of loss of consciousness, will be exclusionary. The MAI who will also retain discretion to exclude based on a history of neurological illness that may compromise data integrity.

Show all 24Show fewer

Have current major psychotic disorders, mania, substance-induced psychiatric disorders, or any current suicidal ideations or history of suicide attempts. Moderate to severe current symptoms of mood or anxiety disorders will be exclusionary as well. However, mild mood or anxiety disorder symptoms will not be exclusionary, whether medicated or unmedicated. The MAI will reserve the right to exclude on the basis of psychiatric history not explicitly described in this criterion. Justification: Psychiatric disorders involve the central neural system (CNS) and, therefore, can be expected to alter the fMRI measures being used in this study, however, some degree of mood and anxiety symptoms are common in community samples of smokers. Assessment tool(s): Computerized SCID or comparable assessment, and clinical interview confirmation by clinician.
Are cognitively impaired or learning disabled. Justification: Cognitive impairment and learning disabilities may be associated with altered brain functioning in regions recruited during laboratory task performance. Cognitive impairment may affect one s ability to give informed consent. Assessment tool(s): History of placement in special-education classes as a consequence of serious learning problems and not solely as a consequence of behavioral problems, assessed during the History and Physical screening assessment.
Have significant cardiovascular conditions that would make use of nicotine patch unsafe. Justification: Nicotine patch may cause significant arrhythmias in susceptible individuals. Assessment tool(s): History and physical exam, including 12-lead EKG.
Have any other major medical condition, such as diabetes mellitus, that in the view of the investigators would compromise the safety of an individual during participation, or the quality of data obtainable. Justification: Many illnesses not explicitly covered here may increase risk or alter important outcome measures. Assessment tool(s): History and physical examination by a qualified IRP clinician and CBC, urinalysis, NIDA chemistry panel (liver function tests, electrolytes, kidney function). The following lab values will result in exclusion from the study:
Hemoglobin < 10 g/dl
White Blood Cell Count < 2400/microl
Liver Function Tests > 3X upper limit of normal
Serum glucose > 200 mg/dl
Urine protein > 2+
Serum creatinine > 2 mg/dl
The MAI will retain discretion to exclude based on less extreme lab results. After the screening process has been completed, the MAI will take into account all data collected in order to decide if there is an existing medical illness that would compromise participation in this research.
Are pregnant, planning to become pregnant, or breastfeeding. Females are instructed in the consent to use effective forms of birth control during the study period. Justification: study procedures and drugs used in the current protocol may complicate pregnancy or be transferred to nursing children. Assessment tool(s): Urine and/or serum pregnancy tests, and clinical interview. Urine pregnancy tests will be conducted at the beginning of each imaging visit.
Are non-English speaking. Justification: To include non-English speakers, we would have to translate the consent and other study documents and hire and train bilingual staff, which would require resources that we do not have and could not justify given the small sample size for each experiment. Additionally, the data integrity of some of the cognitive tasks and standardized questionnaires used in this study would be compromised as they have only been validated in English. Most importantly, ongoing communication regarding safety procedures is necessary when participants are undergoing MRI procedures. The inability to effectively communicate MRI safety procedures in a language other than English could compromise the safety of non-English speaking participants. Assessment tool(s): self-report.
Treatment-seeking smokers will also be excluded if they:
Have moderate to severe renal impairment. Justification. Given that renal secretion is varenicline s major route of clearance, kidney impairment may result in higher systemic levels of the drug than intended. Per Pfizer s chantix insert, varenicline pharmacokinetics were unchanged in subjects with mild renal impairment in comparison to those with normal renal function, whereas individuals with moderate and severe impairment presented with varenicline levels 1.5 and 2.1-fold higher, respectively. Assessment tool(s): Estimated glomerular filtration rate. Renal insufficiency with estimated creatinine clearance < 60 ml/min calculated by the Cockcroft-Gault equation will be excluded.
Are diabetic. Justification. A recent case report describes multiple episodes of severe hypoglycemia experienced by a 51 year old Type-I diabetic after beginning varenicline treatment. The discontinuation of varenicline resolved any further hypoglycemic episodes. The safety of varenicline has not been investigated in patients with diabetes. Assessment tool(s): Casual plasma glucose testing. Individuals with glucose levels above 200 mg/dl may be further evaluated for diabetes using a fasting glucose test or be excluded.
The following exclusion criteria are new for the tDCS study:
Participated in any brain stimulation session less than two weeks ago, or underwent brain stimulation exposure for treatment purposes in the last 6 months, including tDCS or transcranial magnetic stimulation (TMS). Justification: Prior exposure to brain stimulation may result in carry-over effects that could confound the results of this study. Participants may enroll in the study once the listed time periods have passed. Assessment tool(s): Participant medical history and physical (H\&P).

Trial locations and contacts

1 site in 1 country.

United States1 site

National Institute on Drug Abuse
Baltimore, Maryland, 21224

Other trials in United States

About this study

Official title: Identifying Neurobiological Mechanisms That Underlie Acute Nicotine Withdrawal and Drive Early Relapse in Smokers

Background:

Smoking is thought to cause changes in the brain that lead to addiction and craving. Smokers who try to quit experience nicotine withdrawal symptoms that include irritability, anxiety, and difficulty concentrating. These symptoms make it difficult for people to stop smoking. Many people say that they continue smoking to help relieve these symptoms, often within the first week after trying to quit. Researchers want to study what is happening in the brain to cause these symptoms, which may help identify new ways to successfully quit smoking.

Objectives:

To study nicotine withdrawal symptoms and brain function in smokers who stop smoking for 36 hours.

Eligibility:

Individuals between 18 and 65 years of age who smoke at least 10 cigarettes per day. Participants must be able to stop smoking for 36 hours on two occasions.

Design:

Phase 1

This study will involve three visits to the National Institute on Drug Abuse.
NOT be able to smoke for 36 hours before the two imaging visits.
Wear a nicotine skin patch or a placebo (fake) patch during your 36 hour smoking abstinence period and study visits.
Have your blood drawn to test for levels of stress-related hormones.
Complete multiple MRI scanning sessions that last about 1.5 to 2 hours each.
Undergo EEG (brain waves) recording.
Answer questionnaires about how you think and feel.
Complete various tasks and procedures inside and outside of the MRI scanner.

Phase 2

This study will involve thirteen visits to the National Institute on Drug Abuse.
Set a quit date and develop a treatment plan with a study therapist.
Take Chantix (varenicline) every day for a period of 12 weeks.
Meet for weekly and biweekly counseling sessions with a therapist.
Answer questionnaires about how you think and feel.

Phase 3

This study will involve three visits to the National Institute on Drug Abuse.
Complete an MRI scanning session that will last about 20min each visit
Meet with a study staff member on each visit who will ask you questions about your smoking behavior and how you think and feel.

Read the detailed description

Objective

The primary objective of the current protocol is to gain a greater understanding of the neurobiological mechanisms underlying acute nicotine withdrawal and contributing to the maintenance of, or return to smoking behavior among nicotine-dependent individuals, in the service of developing future smoking cessation treatments. The Nicotine Withdrawal Syndrome is a major cause of failed quit attempts in smokers, and targeting this time period for intervention may help improve smoking cessation outcomes.

Study Population

We will recruit treatment seeking and non-treatment seeking smokers, as well as matched non-smoker control participants.

Design

There are 3 arms included in this protocol, each of which aims to understand the neurobiology of the Nicotine Withdrawal Syndrome during the initial quit period, with the broader goal of increasing quit success rate in the future.

Main Study: To understand (1) the acute neurobiological effects of nicotine withdrawal on treatment-seeking and non-treatment seeking smokers, (2) the long term neurobiological outcomes of varenicline treatment and smoking cessation counseling at 1, 6, and 12 months. We will recruit 85 treatment seeking and 35 non-treatment seeking smokers for a within (nicotine deprivation), between (treatment-seeking status) subjects randomized, double blind, placebo controlled study.

Motivational Interviewing Arm: (1) To increase motivation and preparation for smoking cessation treatment among individuals who express an interest in quitting smoking but are not currently ready to enter treatment, in the service of increasing quit success rate and (2) to understand the neurobiological basis of motivation to quit smoking, and the interaction between motivation to quit and mechanisms that underlie acute nicotine withdrawal. We will recruit 300 current smokers interested in quitting smoking, but not yet ready to set a quit date.

Transcranial Direct Current Stimulation (tDCS) Arm: To understand the acute effect of tDCS on 3 large-scale brain networks dysregulated in nicotine addiction and withdrawal, the Default Mode Network, the Executive Control Network, and the Salience Network. We will enroll 60 non-treatment seeking smokers, with the expectation of 35 completers; and enroll 55 non-smoking controls, with the expectation of 45 completers, for a double blind, sham controlled, randomized crossover study. Smokers will be studied in nicotine abstinence and nicotine sated conditions, as in the Main Study design.

Outcome measures

Primary outcome measures:

Change in BOLD signal and FC related to task parameters, between drug (or tDCS) condition.
Behavioral performance on each of the tasks assessing inhibitory control processes, reward responsiveness, amygdala, striatal, BNST reactivity, impulsive decision making, cue reactivity and working memory (e.g., reaction time, error rate, hit rate, reward bias).
Self-reported craving, withdrawal symptoms and mood/affect
Smoking abstinence as determined by self-reported tobacco use, urine cotinine, and breath CO.

Secondary outcome measures:

MRS for glutamate concentration.
Plasma ACTH and cortisol.
Resting state CBF from ASL.
ERP and EEG measures.
Ratings and scores on self-report characterization measures.
Structural MRI and DTI data.
Resting state FC at 1, 6 and 12 months post-treatment.

Conditions: Nicotine Dependence
Being tested: Transcranial Direct Current Stimulation, sham, Nicotine patch, Placebo patch, Varenicline Pill
Keywords: fMRI, tDCS
Medical subject headings: Tobacco Use Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Transcranial Direct Current StimulationDevice
Transcranial Direct Current Stimulation (tDCS), a type of Non-invasive Brain Stimulation (NIBS), has the potential to modify neuronal circuits by application of a subthreshold conductive current through the scalp. Two potential targets for tDCS as a smoking cessation aid are the dorsolateral pre-frontal cortex (dlPFC), a node of the ECN, and the ventromedial prefrontal cortex (vmPFC), a node of the DMN. tDCS can potentially strengthen the control of the ECN through excitatory stimulation of the dlPFC, and weaken the influence of the DMN (Lerman et al 2014) by inhibitory stimulation of the vmPFC. The tDCS model we will use is the neuroConn DC-Stimulator MR (neuroCare Group GmbH, Munchen, Germany).
shamDevice
Sham Comparator
Nicotine patchDrug
Dose-match Nicotine for non-deprived scan
Placebo patchDrug
Nicotine deprived
Varenicline PillDrug
Treatment
Placebo pillDrug
Active comparator to varenicline
Motivational InterviewingBehavioural
Motivational Interviewing for smoking cessation preparation

Study groups in NCT01511614
Study group	Role	What they receive
active tDCS	Active comparator	(1) anodal left-dlPFC + cathodal right-vmPFC stimulation, with anode over the left dlPFC and cathode over the right-vmPFC; (2) cathodal left-dlPFC + anodal right-vmPFC stimulation, in which polarity is reversed between the two electrodes Receives: Device: Transcranial Direct Current Stimulation
sham tDCS	Sham comparator	To simulate the experience of tDCS stimulation, current is ramped on and turned off at the beginning and end of the tDCS session. An additional sham option is to have the current ramp up and down only at the beginning of the sham session, and not at the end. This second sham is supported in the literature as an effective blinding technique, which subjects cannot distinguish from active stimulation (Gandiga et al 2006, Brunoni et al 2012) . One of these sham options will be used for data that will be analyzed together, to be determined based on equipment capabilities and preliminary analysis of blinding efficacy in our cross over design. We will assess the efficacy of sham condition by providing participants and the investigator with a questionnaire on the MRI/tDCS session, wherein they will report whether they thought the tDCS session was active or sham. The MRI operator (or other non protocol personnel) will control active/sham conditions. Receives: Device: sham
Main Study - Treatment	Other	Healthy male and female adults who smokers are actively seeking treatment for smoking cessation were asked to complete three study phases: pre-treatment study visits, treatment visits and post-treatment follow-up visits. Pre-treatment (phase 1): 2 MRI sessions: dose-matched nicotine patch or placebo patch during a 36hr smoking abstinence period completed prior to each. Within ~ 2wks of their second scan visit, participants will have 1-3 pre-treatment preparation visits with a therapist. Treatment (Phase 2): 15-18 visits over ~16-19 weeks. First dose of varenicline (0.5 - 1mg/day), 1 week prior to their quit date followed by 12wks of daily varenicline (2mg/day) as well as weekly and biweekly 30min counseling sessions. Follow-up Phase 3: visits at 1, 6, and 12 months after their last treatment visit to assess quit status and smoking abstinence since last visit, complete a series of state measures and complete a 15-20 min scan session. Receives: Drug: Nicotine patch; Drug: Placebo patch; Drug: Varenicline Pill; Drug: Placebo pill
Main Study - Non-Treatment	Other	Healthy male and female adults who have a history of 1 or more years of consistently smoking cigarettes with a urine cotinine level corresponding to smoker status for the specific test being used, typically corresponding to a urine cotinine above about 200 ng/ml, but who are not currently seeking treatment for smoking cessation. Non-treatment seeking smokers will not set a quit date or make a quit attempt, will not complete a treatment program as part of this study and will not be followed up after they complete the two pre-treatment visits. Receives: Drug: Nicotine patch; Drug: Placebo patch
Main Study - Motivational Interviewing	Other	Current smokers who meet criteria for participation but who are not currently ready to enter treatment for smoking cessation. These subjects will receive motivational interviewing to prepare them for a tobacco cigarette quit attempt. Receives: Behavioral: Motivational Interviewing

What is being measured

The primary outcome is the main question the study is designed to answer.

BOLD Activation in Right ACC During Parametric Flanker Task tDCS Stimulation
BOLD percent signal change in right Anterior Cingulate Cortex (rACC) during parametric flanker task. This table is during 2mA Anodal tDCS at the left Dorsolateral prefrontal cortex (dlPFC), 2mA Cathodal tDCS at left dlPFC, or sham stimulation (i.e. placebo). The 3 task conditions are congruent (i.e. flanker stimuli are identical to target) and medium and high levels of incongruent.
Measured: During tDCS or sham stimulation. Day 1 for non-smokers. Day 1 or 2 for smokers (counterbalanced for nicotine condidtion)
dACC Glutamate
Glutamate measured in the dorsal Anterior Cingulate Cortex (dACC) measured as a ratio to Creatine and Phosphocreatine. Cigarette smokers were 12 hour (overnight) abstinent, and had either a nicotine patch or a placebo patch placed 1-2 hours before scanning.
Measured: 12 hours nicotine abstinent (plus 1-2 hours after patch)
Behavioral Accuracy on N-Back Working Memory Task
Behavioral Performance on N-Back Working Memory Task. Task consisted of 0-back, 1-back and 3-back. In this task, participants respond with a button when the current stimulus is the same as the previous one (1-back), the one 3 stimuli earlier (3-back) or the letter 'D' (0-back) depending upon task condition. Table values are accuracy as a percentage (i.e total times they reponded correctly / total trials). This table is during 2mA Anodal tDCS at the left Dorsolateral prefrontal cortex (dlPFC), 2mA Cathodal tDCS at left dlPFC, or sham stimulation (i.e. placebo).
Measured: During tDCS or sham stimulation. Day 1 for non-smokers. Day 1 or 2 for smokers (counterbalanced for nicotine condition)
Behavioral Reaction Speed on N-Back Working Memory Task
Behavioral Performance on N-Back Working Memory Task. Task consisted of 0-back, 1-back and 3-back. In this task, participants respond with a button when the current stimulus is the same as the previous one (1-back), the one 3 stimuli earlier (3-back) or the letter 'D' (0-back) depending upon task condition. Table values are reaction time speeds. This table is during 2mA Anodal tDCS at the left Dorsolateral prefrontal cortex (dlPFC), 2mA Cathodal tDCS at left dlPFC, or sham stimulation (i.e. placebo).
Measured: During tDCS or sham stimulation. Day 1 for non-smokers. Day 1 or 2 for smokers (counterbalanced for nicotine condition)
Behavioral Accuracy on the Parametric Flanker Task
Behavioral Performance on Parametric Flanker Task. Task consisted of 3 levels of difficulty: congruent trials (where distractors are the same as the target; e.g. HHHHHHH), incongruent2 trials (where the 2 furthest distractors on each side were incongruent with the target; e.g. HHSSSHH) and incongruent3 trials (where all distractors are incongruent with the target; e.g. HHHSHHH). Table values are accuracy as a percentage (i.e total times they reponded correctly / total trials). This table is during 2mA Anodal tDCS at the left Dorsolateral prefrontal cortex (dlPFC), 2mA Cathodal tDCS at left dlPFC, or sham stimulation (i.e. placebo).
Measured: During tDCS or sham stimulation. Day 1 for non-smokers. Day 1 or 2 for smokers (counterbalanced for nicotine condition)
Behavioral Reaction Speed on the Parametric Flanker Task
Behavioral Reaction speed on Parametric Flanker Task. Task consisted of 3 levels of difficulty: congruent trials (where distractors are the same as the target; e.g. HHHHHHH), incongruent2 trials (where the 2 furthest distractors on each side were incongruent with the target; e.g. HHSSSHH) and incongruent3 trials (where all distractors are incongruent with the target; e.g. HHHSHHH). Table values are reaction time speeds. This table is during 2mA Anodal tDCS at the left Dorsolateral prefrontal cortex (dlPFC), 2mA Cathodal tDCS at left dlPFC, or sham stimulation (i.e. placebo).
Measured: During tDCS or sham stimulation. Day 1 for non-smokers. Day 1 or 2 for smokers (counterbalanced for nicotine condition)
Behavioral Accuracy on the Matching Task
Behavioral Performance on the Matching Task. Task consisted of 2 conditions: match faces, where 2 faces appeared at the top of the screen and one at the bottom (target). Participants needed to press a button corresponding to the top row face that matched the target; the control condition was identical, except instead of faces the images consisted of simple shapes (e.g. ovals). Table values are accuracy as a percentage (i.e total times they reponded correctly / total trials). This table is during 2mA Anodal tDCS at the left Dorsolateral prefrontal cortex (dlPFC), 2mA Cathodal tDCS at left dlPFC, or sham stimulation (i.e. placebo).
Measured: During tDCS or sham stimulation. Day 1 for non-smokers. Day 1 or 2 for smokers (counterbalanced for nicotine condition)
Behavioral Reaction Speed on the Matching Task
Behavioral Reaction speed on the Matching Task. Task consisted of 2 conditions: match faces, where 2 faces appeared at the top of the screen and one at the bottom (target). Participants needed to press a button corresponding to the top row face that matched the target; the control condition was identical, except instead of faces the images consisted of simple shapes (e.g. ovals).Table values are reaction time speeds. This table is during 2mA Anodal tDCS at the left Dorsolateral prefrontal cortex (dlPFC), 2mA Cathodal tDCS at left dlPFC, or sham stimulation (i.e. placebo).
Measured: During tDCS or sham stimulation. Day 1 for non-smokers. Day 1 or 2 for smokers (counterbalanced for nicotine condition)
Nicotine Withdrawal From WSWS
Nicotine withdrawal as measured from the total score on the Wisconsin Smoking Withdrawal Scale (WSWS). The WSWS is a 28-item questionnaire ranging from 0 (strongly disagree) to 4 (strongly agree). The total score ranges from 0 to 112, with higher scores indicating more withdrawal symptoms. Cigarette smokers were 12 hour (overnight) abstinent and had either a nicotine patch or a placebo patch placed 1-2 hours before scanning.
Measured: 12 hours nicotine abstinent (plus 1-2 hours after patch)
Nicotine Craving From TCQ-SF
Nicotine craving as measured from the total score on the Tobacco Craving Questionnaire-Short Form (TCQ-SF). The TCQ-SF is a 12-item questionnaire designed to measure craving for cigarettes. Each question is answered on a 7-point scale from 1 (Strongly Disagree) to 7 (Strongly Agree). Total scores range from 12 to 84, with higher scores indicating more craving.
Cigarette smokers were 12 hour (overnight) abstinent and had either a nicotine patch or a placebo patch placed 1-2 hours before scanning.
Measured: 12 hours nicotine abstinent (plus 1-2 hours after patch)
Affect From PANAS
Positive and Negative mood from the Positive and Negative Affect Schedule (PANAS). The PANAS consists of 20 words related to emotions that participants indicate to what extent they felt this way in the last week. Words are rated from 1 (very slightly or not at all) to 5 (extremely). The PANAS is broken into a Positive and Negative subscale, each consisting of 10 questions and thus ranging from 10 to 50. Higher numbers are indicative of higher levels of positive affect and higher levels of negative affect respectively.
Cigarette smokers were 12 hour (overnight) abstinent, and had either a nicotine patch or a placebo patch placed 1-2 hours before scanning.
Measured: 12 hours nicotine abstinent (plus 1-2 hours after patch)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

20 May 201330 Mar 2020

First posted18 Jan 2012 (estimated)
Study start20 May 2013
Primary completion30 Mar 2020
Study completion30 Mar 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Nicotine DependenceStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 112 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01511614
Sponsor's protocol ID: 999912474
Other IDs: 12-DA-N474
Status last verified: 25 Jul 2023
First submitted: 13 Jan 2012
Last updated: 31 May 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Abulseoud OA, Ross TJ, Nam HW, Caparelli EC, Tennekoon M, Schleyer B, Castillo J, Fedota J, Gu H, Yang Y, Stein E. Short-term nicotine deprivation alters dorsal anterior cingulate glutamate concentration and concomitant cingulate-cortical functional connectivity. Neuropsychopharmacology. 2020 Oct;45(11):1920-1930. doi: 10.1038/s41386-020-0741-9. Epub 2020 Jun 19.
PubMed 32559759
Aronson Fischell S, Ross TJ, Deng ZD, Salmeron BJ, Stein EA. Transcranial Direct Current Stimulation Applied to the Dorsolateral and Ventromedial Prefrontal Cortices in Smokers Modifies Cognitive Circuits Implicated in the Nicotine Withdrawal Syndrome. Biol Psychiatry Cogn Neurosci Neuroimaging. 2020 Apr;5(4):448-460. doi: 10.1016/j.bpsc.2019.12.020. Epub 2020 Jan 13.
PubMed 32151567

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
Young Adult Tobacco/Nicotine and Cannabis Co-use
Tobacco Use Disorder, Nicotine Dependence
Recruiting
Social Media Support Groups for Adolescent Vaping Cessation
Vaping, Vaping Cessation
Recruiting
The INITIATE Study: Initiating Nicotine Dependence Treatment for Smokers Admitted to Emergency Departments
Nicotine Dependence, Cigarettes, Nicotine Withdrawal
Recruiting
Advanced Functional and Structural MRI Techniques for Neuropharmacological Imaging
Drug Abuse, Nicotine Dependence
RecruitingObservational study
§SMOKE Nicotine and Tobacco Youth Cohort
Tobacco Use Behavior, Nicotine Dependence Tobacco Product

All Nicotine Dependence trials

Study at a glance

From the registry record, last updated by the sponsor on 31 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Identifying Neurobiological Mechanisms That Underlie Acute Nicotine Withdrawal and Drive Early Relapse in Smokers
ClinicalTrials.gov ID: NCT01511614
Acronym / sponsor ID: 999912474
Conditions: Nicotine Dependence
Keywords: fMRI, tDCS
Study type: Interventional
Recruitment status: Completed
Enrolment: 112 participants (actual)
Lead sponsor: National Institute on Drug Abuse (NIDA)US National Institutes of Health
Study start: 20 May 2013 (actual)
Primary completion: 30 Mar 2020 (actual)
Study completion: 30 Mar 2020 (actual)
First posted: 18 Jan 2012 (estimated)
Results: Posted 31 May 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Background:

Smoking is thought to cause changes in the brain that lead to addiction and craving. Smokers who try to quit experience nicotine withdrawal symptoms that include irritability, anxiety, and difficulty concentrating. These symptoms make it difficult for people to stop smoking. Many people say that they continue smoking to help relieve these symptoms, often within the first week after trying to quit. Researchers want to study what is happening in the brain to cause these symptoms, which may help identify new ways to successfully quit smoking.

Objectives:

To study nicotine withdrawal symptoms and brain function in smokers who stop smoking for 36 hours.

Eligibility:

Individuals between 18 and 65 years of age who smoke at least 10 cigarettes per day. Participants must be able to stop smoking for 36 hours on two occasions.

Design:

Phase 1

This study will involve three visits to the National Institute on Drug Abuse.
NOT be able to smoke for 36 hours before the two imaging visits.
Wear a nicotine skin patch or a placebo (fake) patch during your 36 hour smoking abstinence period and study visits.
Have your blood drawn to test for levels of stress-related hormones.
Complete multiple MRI scanning sessions that last about 1.5 to 2 hours each.
Undergo EEG (brain waves) recording.
Answer questionnaires about how you think and feel.
Complete various tasks and procedures inside and outside of the MRI scanner.

Phase 2

This study will involve thirteen visits to the National Institute on Drug Abuse.
Set a quit date and develop a treatment plan with a study therapist.
Take Chantix (varenicline) every day for a period of 12 weeks.
Meet for weekly and biweekly counseling sessions with a therapist.
Answer questionnaires about how you think and feel.

Phase 3

This study will involve three visits to the National Institute on Drug Abuse.
Complete an MRI scanning session that will last about 20min each visit
Meet with a study staff member on each visit who will ask you questions about your smoking behavior and how you think and feel.

Detailed description

Objective

Study Population

We will recruit treatment seeking and non-treatment seeking smokers, as well as matched non-smoker control participants.

Design

Outcome measures

Primary outcome measures:

Change in BOLD signal and FC related to task parameters, between drug (or tDCS) condition.
Behavioral performance on each of the tasks assessing inhibitory control processes, reward responsiveness, amygdala, striatal, BNST reactivity, impulsive decision making, cue reactivity and working memory (e.g., reaction time, error rate, hit rate, reward bias).
Self-reported craving, withdrawal symptoms and mood/affect
Smoking abstinence as determined by self-reported tobacco use, urine cotinine, and breath CO.

Secondary outcome measures:

MRS for glutamate concentration.
Plasma ACTH and cortisol.
Resting state CBF from ASL.
ERP and EEG measures.
Ratings and scores on self-report characterization measures.
Structural MRI and DTI data.
Resting state FC at 1, 6 and 12 months post-treatment.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 5

Arm	Type	Receives
active tDCS	Active comparator	Device: Transcranial Direct Current Stimulation(1) anodal left-dlPFC + cathodal right-vmPFC stimulation, with anode over the left dlPFC and cathode over the right-vmPFC; (2) cathodal left-dlPFC + anodal right-vmPFC stimulation, in which polarity is reversed between the two electrodes
sham tDCS	Sham comparator	Device: shamTo simulate the experience of tDCS stimulation, current is ramped on and turned off at the beginning and end of the tDCS session. An additional sham option is to have the current ramp up and down only at the beginning of the sham session, and not at the end. This second sham is supported in the literature as an effective blinding technique, which subjects cannot distinguish from active stimulation (Gandiga et al 2006, Brunoni et al 2012) . One of these sham options will be used for data that will be analyzed together, to be determined based on equipment capabilities and preliminary analysis of blinding efficacy in our cross over design. We will assess the efficacy of sham condition by providing participants and the investigator with a questionnaire on the MRI/tDCS session, wherein they will report whether they thought the tDCS session was active or sham. The MRI operator (or other non protocol personnel) will control active/sham conditions.
Main Study - Treatment	Other	Drug: Nicotine patch, Drug: Placebo patch, Drug: Varenicline Pill, Drug: Placebo pillHealthy male and female adults who smokers are actively seeking treatment for smoking cessation were asked to complete three study phases: pre-treatment study visits, treatment visits and post-treatment follow-up visits. Pre-treatment (phase 1): 2 MRI sessions: dose-matched nicotine patch or placebo patch during a 36hr smoking abstinence period completed prior to each. Within ~ 2wks of their second scan visit, participants will have 1-3 pre-treatment preparation visits with a therapist. Treatment (Phase 2): 15-18 visits over ~16-19 weeks. First dose of varenicline (0.5 - 1mg/day), 1 week prior to their quit date followed by 12wks of daily varenicline (2mg/day) as well as weekly and biweekly 30min counseling sessions. Follow-up Phase 3: visits at 1, 6, and 12 months after their last treatment visit to assess quit status and smoking abstinence since last visit, complete a series of state measures and complete a 15-20 min scan session.
Main Study - Non-Treatment	Other	Drug: Nicotine patch, Drug: Placebo patchHealthy male and female adults who have a history of 1 or more years of consistently smoking cigarettes with a urine cotinine level corresponding to smoker status for the specific test being used, typically corresponding to a urine cotinine above about 200 ng/ml, but who are not currently seeking treatment for smoking cessation. Non-treatment seeking smokers will not set a quit date or make a quit attempt, will not complete a treatment program as part of this study and will not be followed up after they complete the two pre-treatment visits.
Main Study - Motivational Interviewing	Other	Behavioral: Motivational InterviewingCurrent smokers who meet criteria for participation but who are not currently ready to enter treatment for smoking cessation. These subjects will receive motivational interviewing to prepare them for a tobacco cigarette quit attempt.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

Be between the ages of 18-65.
Be right-handed. Assessment tool(s): Edinburgh Handedness Inventory.
Be in good health. Justification: Many illnesses may alter fMRI signals as well as cognitive processes and neural functioning. Assessment tool(s): Participants will provide a brief health history during phone screening, and undergo a medical history and physical examination with a qualified IRP clinician.
Be free of current moderate to severe DSM-V Substance Use Disorder on any drug, except nicotine in smokers. Those with past moderate to severe use disorder on substances may be included, provided they are in sustained remission (and not on maintenance therapy for opioid use disorder) and are not intoxicated on the day of the imaging session. Justification: Moderate to severe use disorder on other substances may result in unique CNS deficits that could confound results and introduce excessive variance, while mild substance use disorder and substance use disorder in remission are common in community samples of smokers. Assessment tool(s): Computerized SCID or comparable assessment and DSM-5 substance use disorder assessment.
Be able to abstain from alcohol and other recreational drugs for 24 hours before each imaging session, and able to moderate caffeine intake 12 hours before each imaging session. Justification: Recent substance use, including alcohol, and caffeine modulate neural functioning in a way that would complicate data interpretation. Assessment tool(s): Self-report, breathalyzer, and urine toxicology screen with follow up neuromotor assessment to ensure absence of acute impairment with positive urine test.

Key exclusion criteria (24 listed)

Are not suitable to undergo an fMRI experiment due to certain implanted devices (cardiac pacemaker or neurostimulator, some artificial joints, metal pins, surgical clips or other implanted metal parts), body morphology, or claustrophobia. Justification: MR scanning is one of the primary measurement tools used in the protocol. Assessment tool(s): Prospective participants will fill out an MRI screening questionnaire and undergo an interview with an MR technologist. Questions concerning suitability for scanning will be referred to the MR Medical Safety Officer. Prospective participants will be questioned about symptoms of claustrophobia and placed in the mock scanner during their first visit to assess for possible difficulty tolerating the confinement of the scanner and for ability to fit into the scanner.
Have musculoskeletal abnormalities restricting an individual s ability to lie flat for extended periods of time. Justification: MR scanning sessions require participants to lie flat on their backs and remain perfectly still for approximately one hour. Therefore, conditions that would make that difficult (e.g. chronic back pain, significant scoliosis) will be exclusionary. Assessment tool(s): History and physical examination by a qualified IRP clinician, supplemented with a trial of lying in the mock scanner to assess comfort issues.
Have HIV or Syphilis. Justification: HIV and Syphilis both can have central nervous system (CNS) sequelae, thus introducing unnecessary variability into the data. Assessment tool(s): Oral HIV followed by blood test if oral test is + and STS+ without adequate prior treatment
Regularly or intermittently use any prescription (e.g., benzodiazepines, barbiturates), over-the-counter (e.g., cold medicine) medications that are likely to alter BOLD signal (neuronal-vascular coupling). Justification: The use of these substances may alter the fMRI signal and/or neural functions of interest in the current study. Assessment tool(s): History and comprehensive urine drug screening to detect benzodiazepines, antipsychotics, anticonvulsants, and barbiturates. Note: If a participant is intermittently taking a medication likely to affect BOLD signal, the participant may be excluded or if scanned, will be scanned in the same medication state for data continuity purposes (i.e. either all scan days are scheduled after 5 half-lives since last medication use; or all scan days are scheduled on medication).
Have any current neurological illnesses including, but not limited to, seizure disorders, frequent migraines or on prophylaxis, multiple sclerosis, cerebrovascular accident, movement disorders (except essential tremor, so long as it would not interfere with study tasks such as button pressing), history of significant head trauma, or CNS tumor. Justification: Neurological diseases alter CNS function and, possibly, the neuronal-vascular coupling that forms the basis of the fMRI signal. Assessment tool(s): History and physical examination by a qualified IRP clinician, urine drug screening for anticonvulsants not disclosed by history. History of head trauma with loss of consciousness of more than 30 minutes or with post-concussive sequelae lasting more than two days, regardless of loss of consciousness, will be exclusionary. The MAI who will also retain discretion to exclude based on a history of neurological illness that may compromise data integrity.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Transcranial Direct Current StimulationTranscranial Direct Current Stimulation (tDCS), a type of Non-invasive Brain Stimulation (NIBS), has the potential to modify neuronal circuits by application of a subthreshold conductive current through the scalp. Two potential targets for tDCS as a smoking cessation aid are the dorsolateral pre-frontal cortex (dlPFC), a node of the ECN, and the ventromedial prefrontal cortex (vmPFC), a node of the DMN. tDCS can potentially strengthen the control of the ECN through excitatory stimulation of the dlPFC, and weaken the influence of the DMN (Lerman et al 2014) by inhibitory stimulation of the vmPFC. The tDCS model we will use is the neuroConn DC-Stimulator MR (neuroCare Group GmbH, Munchen, Germany).	Device	active tDCS
shamSham Comparator	Device	sham tDCS
Nicotine patchDose-match Nicotine for non-deprived scan	Drug	Main Study - Non-Treatment, Main Study - Treatment
Placebo patchNicotine deprived	Drug	Main Study - Non-Treatment, Main Study - Treatment
Varenicline PillTreatment	Drug	Main Study - Treatment
Placebo pillActive comparator to varenicline	Drug	Main Study - Treatment
Motivational InterviewingMotivational Interviewing for smoking cessation preparation	Behavioural	Main Study - Motivational Interviewing

Primary outcome

BOLD Activation in Right ACC During Parametric Flanker Task tDCS Stimulation
Time frame: During tDCS or sham stimulation. Day 1 for non-smokers. Day 1 or 2 for smokers (counterbalanced for nicotine condidtion)
BOLD percent signal change in right Anterior Cingulate Cortex (rACC) during parametric flanker task. This table is during 2mA Anodal tDCS at the left Dorsolateral prefrontal cortex (dlPFC), 2mA Cathodal tDCS at left dlPFC, or sham stimulation (i.e. placebo). The 3 task conditions are congruent (i.e. flanker stimuli are identical to target) and medium and high levels of incongruent.
dACC Glutamate
Time frame: 12 hours nicotine abstinent (plus 1-2 hours after patch)
Glutamate measured in the dorsal Anterior Cingulate Cortex (dACC) measured as a ratio to Creatine and Phosphocreatine. Cigarette smokers were 12 hour (overnight) abstinent, and had either a nicotine patch or a placebo patch placed 1-2 hours before scanning.
Behavioral Accuracy on N-Back Working Memory Task
Time frame: During tDCS or sham stimulation. Day 1 for non-smokers. Day 1 or 2 for smokers (counterbalanced for nicotine condition)
Behavioral Performance on N-Back Working Memory Task. Task consisted of 0-back, 1-back and 3-back. In this task, participants respond with a button when the current stimulus is the same as the previous one (1-back), the one 3 stimuli earlier (3-back) or the letter 'D' (0-back) depending upon task condition. Table values are accuracy as a percentage (i.e total times they reponded correctly / total trials). This table is during 2mA Anodal tDCS at the left Dorsolateral prefrontal cortex (dlPFC), 2mA Cathodal tDCS at left dlPFC, or sham stimulation (i.e. placebo).
Behavioral Reaction Speed on N-Back Working Memory Task
Time frame: During tDCS or sham stimulation. Day 1 for non-smokers. Day 1 or 2 for smokers (counterbalanced for nicotine condition)
Behavioral Performance on N-Back Working Memory Task. Task consisted of 0-back, 1-back and 3-back. In this task, participants respond with a button when the current stimulus is the same as the previous one (1-back), the one 3 stimuli earlier (3-back) or the letter 'D' (0-back) depending upon task condition. Table values are reaction time speeds. This table is during 2mA Anodal tDCS at the left Dorsolateral prefrontal cortex (dlPFC), 2mA Cathodal tDCS at left dlPFC, or sham stimulation (i.e. placebo).
Behavioral Accuracy on the Parametric Flanker Task
Time frame: During tDCS or sham stimulation. Day 1 for non-smokers. Day 1 or 2 for smokers (counterbalanced for nicotine condition)
Behavioral Performance on Parametric Flanker Task. Task consisted of 3 levels of difficulty: congruent trials (where distractors are the same as the target; e.g. HHHHHHH), incongruent2 trials (where the 2 furthest distractors on each side were incongruent with the target; e.g. HHSSSHH) and incongruent3 trials (where all distractors are incongruent with the target; e.g. HHHSHHH). Table values are accuracy as a percentage (i.e total times they reponded correctly / total trials). This table is during 2mA Anodal tDCS at the left Dorsolateral prefrontal cortex (dlPFC), 2mA Cathodal tDCS at left dlPFC, or sham stimulation (i.e. placebo).
Behavioral Reaction Speed on the Parametric Flanker Task
Time frame: During tDCS or sham stimulation. Day 1 for non-smokers. Day 1 or 2 for smokers (counterbalanced for nicotine condition)
Behavioral Reaction speed on Parametric Flanker Task. Task consisted of 3 levels of difficulty: congruent trials (where distractors are the same as the target; e.g. HHHHHHH), incongruent2 trials (where the 2 furthest distractors on each side were incongruent with the target; e.g. HHSSSHH) and incongruent3 trials (where all distractors are incongruent with the target; e.g. HHHSHHH). Table values are reaction time speeds. This table is during 2mA Anodal tDCS at the left Dorsolateral prefrontal cortex (dlPFC), 2mA Cathodal tDCS at left dlPFC, or sham stimulation (i.e. placebo).
Behavioral Accuracy on the Matching Task
Time frame: During tDCS or sham stimulation. Day 1 for non-smokers. Day 1 or 2 for smokers (counterbalanced for nicotine condition)
Behavioral Performance on the Matching Task. Task consisted of 2 conditions: match faces, where 2 faces appeared at the top of the screen and one at the bottom (target). Participants needed to press a button corresponding to the top row face that matched the target; the control condition was identical, except instead of faces the images consisted of simple shapes (e.g. ovals). Table values are accuracy as a percentage (i.e total times they reponded correctly / total trials). This table is during 2mA Anodal tDCS at the left Dorsolateral prefrontal cortex (dlPFC), 2mA Cathodal tDCS at left dlPFC, or sham stimulation (i.e. placebo).
Behavioral Reaction Speed on the Matching Task
Time frame: During tDCS or sham stimulation. Day 1 for non-smokers. Day 1 or 2 for smokers (counterbalanced for nicotine condition)
Behavioral Reaction speed on the Matching Task. Task consisted of 2 conditions: match faces, where 2 faces appeared at the top of the screen and one at the bottom (target). Participants needed to press a button corresponding to the top row face that matched the target; the control condition was identical, except instead of faces the images consisted of simple shapes (e.g. ovals).Table values are reaction time speeds. This table is during 2mA Anodal tDCS at the left Dorsolateral prefrontal cortex (dlPFC), 2mA Cathodal tDCS at left dlPFC, or sham stimulation (i.e. placebo).
Nicotine Withdrawal From WSWS
Time frame: 12 hours nicotine abstinent (plus 1-2 hours after patch)
Nicotine withdrawal as measured from the total score on the Wisconsin Smoking Withdrawal Scale (WSWS). The WSWS is a 28-item questionnaire ranging from 0 (strongly disagree) to 4 (strongly agree). The total score ranges from 0 to 112, with higher scores indicating more withdrawal symptoms. Cigarette smokers were 12 hour (overnight) abstinent and had either a nicotine patch or a placebo patch placed 1-2 hours before scanning.
Nicotine Craving From TCQ-SF
Time frame: 12 hours nicotine abstinent (plus 1-2 hours after patch)
Nicotine craving as measured from the total score on the Tobacco Craving Questionnaire-Short Form (TCQ-SF). The TCQ-SF is a 12-item questionnaire designed to measure craving for cigarettes. Each question is answered on a 7-point scale from 1 (Strongly Disagree) to 7 (Strongly Agree). Total scores range from 12 to 84, with higher scores indicating more craving. Cigarette smokers were 12 hour (overnight) abstinent and had either a nicotine patch or a placebo patch placed 1-2 hours before scanning.
Affect From PANAS
Time frame: 12 hours nicotine abstinent (plus 1-2 hours after patch)
Positive and Negative mood from the Positive and Negative Affect Schedule (PANAS). The PANAS consists of 20 words related to emotions that participants indicate to what extent they felt this way in the last week. Words are rated from 1 (very slightly or not at all) to 5 (extremely). The PANAS is broken into a Positive and Negative subscale, each consisting of 10 questions and thus ranging from 10 to 50. Higher numbers are indicative of higher levels of positive affect and higher levels of negative affect respectively. Cigarette smokers were 12 hour (overnight) abstinent, and had either a nicotine patch or a placebo patch placed 1-2 hours before scanning.

Results and safety

Results posted to the registry on 31 May 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Main Study - Treatment	14	3
Main Study - Non-Treatment	28	19
Main Study - Motivational Interviewing	2	2
tDCS Arm - Smoker	32	19
tDCS - Non-Smoker	33	30
tDCS - Behavioral Pilot	3	3

Primary outcome: BOLD Activation in Right ACC During Parametric Flanker Task tDCS Stimulation

Time frame: During tDCS or sham stimulation. Day 1 for non-smokers. Day 1 or 2 for smokers (counterbalanced for nicotine condidtion). Mean (Standard Deviation). Unit: Percent BOLD change

Measure	tDCS Arm - Non-smoker n = 28	tDCS Arm - Sated Smoker n = 15	tDCS Arm - Placebo Smoker n = 15
Anodal left dlPFC stimulation, task congruent	1.051567464 (0.613503334)	0.867749333 (0.632271673)	0.8973946 (0.764795369)
Anodal left dlPFC stimulation, task medium incongruent	1.143702607 (0.792691244)	1.1765768 (0.707165736)	1.0322936 (0.970342615)
Anodal left dlPFC stimulation, task high incongruent	1.338308679 (0.765383086)	1.392077933 (0.818806467)	1.154613533 (1.057797744)
Cathodal left dlPFC stimulation, task congruent	0.925731857 (0.73461226)	0.863549133 (0.862738124)	1.062994933 (0.992544203)
Cathodal left dlPFC stimulation, task medium incongruent	0.960205786 (0.738140954)	0.986851467 (0.895053512)	1.258576333 (1.087900913)
Cathodal left dlPFC stimulation, task high incongruent	1.161453536 (0.74433763)	1.243763333 (0.985162535)	1.451806467 (1.160555321)
Sham stimulation, task congruent	1.025226143 (0.527038736)	0.6320986 (0.476573713)	0.968123333 (0.691987432)
Sham stimulation, task medium incongruent	1.073017964 (0.700394341)	0.800749733 (0.653128921)	1.046178533 (0.907522718)

Primary outcome: dACC Glutamate

Time frame: 12 hours nicotine abstinent (plus 1-2 hours after patch). Mean (Standard Error). Unit: ratio to Cr+PCr

Measure	Main Arm - Sated Smoker n = 30	Main Arm - Withdrawn Smoker n = 30
Value	1.5 (.03)	1.54 (.029)

Population analysed: Note that the treatment part of the main arm did not take place. As a consequence, all procedures performed were identical for both 'main arm - treatment' and 'main arm - non-treatment'. As these groups are thus identical, they are combined herein.

Primary outcome: Behavioral Accuracy on N-Back Working Memory Task

Time frame: During tDCS or sham stimulation. Day 1 for non-smokers. Day 1 or 2 for smokers (counterbalanced for nicotine condition). Mean (Standard Deviation). Unit: Percent Correct

Measure	tDCS Arm - Non-smoker n = 28	tDCS Arm - Sated Smoker n = 15	tDCS Arm - Withdrawn Smoker n = 15
Percent Correct - Anodal left dlPFC stimulation, task Zero-Back Condition	91.43 (15.11)	97.56 (5.27)	94.67 (5.75)
Percent Correct - Anodal left dlPFC stimulation, task One-Back Condition	89.88 (13.47)	93.33 (10.84)	87.11 (11.88)
Percent Correct - Anodal left dlPFC stimulation, task Three-Back Condition	58.93 (16.88)	67.11 (18.89)	58.89 (16.79)
Percent Correct - Cathodal left dlPFC stimulation, task Zero-Back Condition	94.40 (7.65)	98.00 (3.74)	85.11 (15.83)
Percent Correct - Cathodal left dlPFC stimulation, task One-Back Condition	89.40 (12.00)	91.78 (9.83)	80.22 (20.41)
Percent Correct - Cathodal left dlPFC stimulation, task Three-Back Condition	59.52 (14.28)	69.78 (18.28)	54.00 (15.18)
Percent Correct - Sham stimulation, task Zero-Back Condition	89.88 (21.27)	94.89 (13.21)	90.89 (10.80)
Percent Correct - Sham stimulation, task One-Back Condition	88.81 (16.81)	94.00 (7.04)	82.22 (17.31)

Primary outcome: Behavioral Reaction Speed on N-Back Working Memory Task

Time frame: During tDCS or sham stimulation. Day 1 for non-smokers. Day 1 or 2 for smokers (counterbalanced for nicotine condition). Mean (Standard Deviation). Unit: 1/sec

Measure	tDCS Arm - Non-smoker n = 28	tDCS Arm - Sated Smoker n = 15	tDCS Arm - Withdrawn Smoker n = 15
Reaction speed - Anodal left dlPFC stimulation, task Zero-Back Condition	2.24 (.35)	2.36 (.33)	2.20 (.34)
Reaction speed - Anodal left dlPFC stimulation, task One-Back Condition	2.13 (.44)	2.22 (.28)	2.05 (.41)
Reaction speed - Anodal left dlPFC stimulation, task Three-Back Condition	1.91 (.59)	1.78 (.44)	1.64 (.49)
Reaction speed - Cathodal left dlPFC stimulation, task Zero-Back Condition	2.26 (.39)	2.35 (.36)	2.29 (.28)
Reaction speed - Cathodal left dlPFC stimulation, task One-Back Condition	2.16 (.51)	2.28 (.36)	2.07 (.36)
Reaction speed - Cathodal left dlPFC stimulation, task Three-Back Condition	1.85 (.63)	1.82 (.41)	1.62 (.39)
Reaction speed - Sham stimulation, task Zero-Back Condition	2.22 (.37)	2.25 (.37)	2.24 (.30)
Reaction speed - Sham stimulation, task One-Back Condition	2.11 (.52)	2.17 (.42)	2.04 (.40)

Adverse events

Time frame: From baseline to Scan 2 for tDCS Smoker arm (including behavioral pilot). Approximately 1 week to 3 months total. From Scan 1 to Scan 2 for tDCS non-smoker arm (including behavioral pilot). Approximately 1 week to 3 months total. From Phase 1 (pre-treatment study visits) to Phase 3 (follow-up visits) for Treatment arm. Approximately 1 - 1.5 years total. Phase 1 only for non-treatment arm. Approximately 3 - 5 weeks total.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Main Study - Treatment	0 of 14 (0%)	0 of 14 (0%)	0 of 14
Main Study - Non-Treatment	0 of 28 (0%)	5 of 28 (17.9%)	0 of 28
Main Study - Motivational Interviewing Arm	0 of 2 (0%)	0 of 2 (0%)	0 of 2
tDCS Arm - Smoker	0 of 32 (0%)	7 of 32 (21.9%)	0 of 32
tDCS Arm - Non-Smoker	0 of 33 (0%)	3 of 33 (9.1%)	0 of 33
tDCS Arm - Behavioral Pilot	0 of 3 (0%)	0 of 3 (0%)	0 of 3

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 32559759Abulseoud OA, Ross TJ, Nam HW, Caparelli EC, Tennekoon M, Schleyer B, Castillo J, Fedota J, Gu H, Yang Y, Stein E. Short-term nicotine deprivation alters dorsal anterior cingulate glutamate concentration and concomitant cingulate-cortical functional connectivity. Neuropsychopharmacology. 2020 Oct;45(11):1920-1930. doi: 10.1038/s41386-020-0741-9. Epub 2020 Jun 19.
Results publication: PubMed 32151567Aronson Fischell S, Ross TJ, Deng ZD, Salmeron BJ, Stein EA. Transcranial Direct Current Stimulation Applied to the Dorsolateral and Ventromedial Prefrontal Cortices in Smokers Modifies Cognitive Circuits Implicated in the Nicotine Withdrawal Syndrome. Biol Psychiatry Cogn Neurosci Neuroimaging. 2020 Apr;5(4):448-460. doi: 10.1016/j.bpsc.2019.12.020. Epub 2020 Jan 13.
Individual participant dataSharing planned: No

Related trials for Nicotine Dependence

Recruiting
Young Adult Tobacco/Nicotine and Cannabis Co-use
Tobacco Use Disorder, Nicotine Dependence
Recruiting
Social Media Support Groups for Adolescent Vaping Cessation
Vaping, Vaping Cessation
Recruiting
The INITIATE Study: Initiating Nicotine Dependence Treatment for Smokers Admitted to Emergency Departments
Nicotine Dependence, Cigarettes, Nicotine Withdrawal
Recruiting
Advanced Functional and Structural MRI Techniques for Neuropharmacological Imaging
Drug Abuse, Nicotine Dependence
RecruitingObservational study
§SMOKE Nicotine and Tobacco Youth Cohort
Tobacco Use Behavior, Nicotine Dependence Tobacco Product

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Amy Janes, Ph.D. principal investigator

National Institute on Drug Abuse (NIDA)

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

BOLD Activation in Right ACC During Parametric Flanker Task tDCS Stimulation (time frame: During tDCS or sham stimulation. Day 1 for non-smokers. Day 1 or 2 for smokers (counterbalanced for nicotine condidtion)). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01511614, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 May 2024.