Nicotine AddictionNCT02837510
Neural Mechanisms Associated With Risk of Smoking Relapse
A study testing Standard smoking cessation counseling in people with Nicotine Addiction, run by University of Pennsylvania at 1 site in United States.
Trial summary
This study will examine how abstinence-induced brain changes contribute to smoking cessation outcomes in treatment-seeking smokers. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Nicotine Addiction
- What is being tested?
- Standard smoking cessation counseling
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 119 participants
- Where
- 1 siteUnited States
- Study dates
- May 2016to 1 Jun 2024
- 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
- Eligible participants will be:
- Treatment-seeking smokers between the ages of 18 and 65, reporting consumption of at least 5 cigarettes per day for at least the past 6 months;
- Planning to live in the area for at least the next 3 months;
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the combined consent and HIPAA form;
- Able to communicate fluently in English (speaking, writing, and reading).
Who cannot join
- Subjects who present and/or self-report with the following criteria at any point during study participation will not be eligible to participate in the study:
- Smoking Behavior:
- Use of chewing tobacco or snuff or cigars;
- Current enrollment or plans to enroll in another smoking cessation program or research study in the next 3 months;
- Current or anticipated (within the next 3 months) use of smoking cessation medications or nicotine replacement therapy (NRT);
- A baseline carbon monoxide (CO) reading less than or equal to 8ppm.
Show all 46Show fewer
- Alcohol/Drugs:
- Diagnosis or treatment for alcohol or drug abuse in the past two years as reported during phone screen (e.g., alcohol, opioids, cocaine, or stimulants);
- Current alcohol consumption that exceeds 25 standard drinks/week;
- Positive breath alcohol concentration test (BrAC greater than or equal to 0.01) at intake;
- Participants testing positive for breath alcohol with a reading equal to or greater than .08 (the legal driving limit) or who are visibly impaired will be instructed not to drive themselves home after the appointment. If a participant needs to use a phone to call for a safe ride home, an office telephone will be made available to the participant.
- A positive urine drug screen for cocaine, opiates, PCP, benzodiazepines, methadone, MDMA, amphetamine, methamphetamine, tri-cyclic antidepressants and/or barbiturates at any session;
- Medication:
- Current use or recent discontinuation (within the past 30 days at the time of Intake) of:
- Smoking cessation medication (e.g., Zyban, Wellbutrin, Wellbutrin SR, Chantix, NRT);
- Anti-psychotic medications;
- Anti-depressants (tricyclics, SSRI's, selective and nonselective MAOIs, Wellbutrin/Zyban);
- Anti-anxiety agents;
- Anti-panic agents;
- Prescription (e.g., Provigil, Ritalin) or over-the-counter stimulants;
- Prescription sleep aids (e.g., Ambien, Lunesta) if used more than 2x/week. If participants report use less than twice a week, they will just be asked to refrain from use during imaging portion of the study.
- Any medication that could compromise participant safety as determined by the Principal Investigator and/or Study Physician;
- Daily use of:
- Opiate-containing medications for chronic pain.
- Medical/Neuropsychiatric:
- Women who are pregnant, planning a pregnancy, and/or breast feeding. All female subjects of childbearing potential will undergo a urine pregnancy test at Intake and both fMRI scan visits (3 urine pregnancy tests in total).
- History of epilepsy or a seizure disorder;
- History of stroke;
- Self-reported brain or spinal tumor;
- Self-reported history or current diagnosis of psychosis, bipolar disorder, schizophrenia, current major depression (subjects with a history of major depression but in remission for past 6 months are eligible), or any Axis 1 disorder.
- fMRI-Related:
- Self-reported history of head trauma;
- Self-reported brain (or CNS) or spinal tumor;
- Self-reported use of pacemakers, certain metallic implants, or presence of metal in the eye as contraindicated for fMRI;
- Self-reported history of claustrophobia;
- Being left-handed;
- Color blindness;
- Weight greater than 299lbs;
- Self-reported history of gunshot wounds;
- Any impairment preventing participants from using the response pad necessary for the cognitive testing;
- Circumstances or conditions that may interfere with magnetic resonance imaging (MRI).
- General Exclusion:
- Any medical condition, illness, disorder, or concomitant medication that could compromise participant safety or treatment, as determined by the Principal Investigator;
- Low or borderline intellectual functioning - determined by a score of less than 85 on the Shipley Institute of Living Scale (SILS) (administered at Intake Visit);
- Enrollment or plans to enroll in another research study;
- Inability to provide informed consent or complete any of the study tasks as determined by the Principal Investigator.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
This study will examine how abstinence-induced brain changes contribute to smoking cessation outcomes in treatment-seeking smokers.
Read the detailed description
Smoking is the greatest preventable cause of mortality and a significant economic burden. Even with the best available treatments, most smokers relapse within days or weeks after a quit attempt. Nicotine replacement therapy, the most widely used pharmacotherapy, yields end of treatment quit rates of <25% suggesting that managing nicotine withdrawal is not sufficient. To improve quit rates significantly, a more refined mechanistic understanding is needed. Neuroimaging can identify mechanisms underlying behavior change beyond self-report and behavioral measures. Functional magnetic resonance imaging (fMRI) studies show that brief (e.g., 24 hr.) abstinence from smoking produces working memory deficits associated with reduced neural activity in cognitive control circuits. This study will examine how abstinence-induced brain changes contribute to clinical outcomes in treatment-seeking smokers. Using a validated fMRI abstinence challenge paradigm, 200 treatment-seeking smokers will complete two 1-hour pre-treatment fMRI scans: after smoking satiety and after 24 hours of confirmed abstinence. Approximately 50% of participants will complete the smoking session first, followed by the absence session, and the remainder will complete the opposite order (counterbalanced). The investigators will examine brain responses during the performance of tasks probing working memory. Participants will then set a target quit date, receive smoking cessation counseling, and be monitored for 6 months to assess time to relapse using a validated smoking relapse protocol.
- Conditions
- Nicotine Addiction
- Being tested
- Standard smoking cessation counseling
- 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.
Standard smoking cessation counselingBehavioural
Participants will discuss reasons for quitting, the model of smoking as a learned habit, triggers for smoking, and trigger management; receive brief training in how to manage withdrawal symptoms and relapse prevention counseling and receive the NCI Clearing the Air self-help smoking cessation booklet. The target quit date (TQD) session will be scheduled to occur up to 2 weeks following the pre-quit session. Participants will then meet with a smoking cessation counselor for a 15 minute booster counseling session. During the first week following TQD there will be two monitoring visits to closely monitor abstinence. Weekly thereafter for four weeks, participants will attend a brief booster counseling session.
| Study group | Role | What they receive |
|---|---|---|
| Standard smoking cessation counseling | Other | Participants will receive a standard treatment program consisting of smoking cessation counseling. Receives: Behavioral: Standard smoking cessation counseling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Days to Relapse
The primary outcome will be the number of days to relapse following the target quit date. Relapse will be confirmed using a conventional SRNT guideline criterion of either a positive biochemical verification of smoking or 7 consecutive days of smoking based on self-report (it is very unlikely that a subject would meet the latter criterion without also meeting the former, given the long half-life of cotinine). The days to relapse will be based upon time from target quit date to the first day of the relapse period. Self-reported daily smoking data will be collected using a validated timeline follow-back method. Self-reported abstinence will be biochemically verified on a weekly basis using urine cotinine (<100ng/ml) and a CO reading of ≤5PPM. Drop-outs will be considered relapsers following the last date of abstinence data provided.
Measured: 6 months after target quit date
Secondary outcomes (1)
Brain Activation (BOLD Percent Signal Change)
To measure the effects of acute 24-hour abstinence from smoking on executive function, functional magnetic resonance imaging (fMRI) was utilized to assess the relative importance of dorsolateral prefrontal cortex (left DLPFC, right DLPFC), Medial Frontal/Cingulate Gyrus (MF/CG), Posterior Cingulate Cortex (PCC) and Prefrontal cortex (PFC) blood oxygen dependent (BOLD) signals during working memory task performance. Measurement of BOLD percent signal change range is 0 to 2%. Percent signal change is the difference in fMRI signal between the baseline condition (B) and the task condition (T) and calculated here as: percent signal change = (T-B)/B×100%. Greater percent signal change in the DLPFC, MF/CG, PCC, and PFC is generally associated with better executive function.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2016 (estimated)
- Study startMay 2016
- Primary completion1 Jun 2023
- Study completion1 Jun 2024
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 (1)Papers the sponsor has linked to this study.
- Other trials for Nicotine AddictionStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 119 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- James Loughead, Ph.D., Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02837510
- Sponsor's protocol ID
- 824061
- Other IDs
- 5R01DA041402
- Status last verified
- Feb 2025
- First submitted
- 3 Jun 2016
- Last updated
- 5 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Allenby C, Falcone M, Wileyto EP, Cao W, Bernardo L, Ashare RL, Janes A, Loughead J, Lerman C. Neural cue reactivity during acute abstinence predicts short-term smoking relapse. Addict Biol. 2020 Mar;25(2):e12733. doi: 10.1111/adb.12733. Epub 2019 Feb 25.
PubMed 30806013
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neural Mechanisms Associated With Risk of Smoking Relapse
- ClinicalTrials.gov ID
- NCT02837510
- Acronym / sponsor ID
- 824061
- Conditions
- Nicotine Addiction
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 119 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- May 2016 (actual)
- Primary completion
- 1 Jun 2023 (actual)
- Study completion
- 1 Jun 2024 (actual)
- First posted
- 19 Jul 2016 (estimated)
- Results
- Posted 5 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will examine how abstinence-induced brain changes contribute to smoking cessation outcomes in treatment-seeking smokers.
Detailed description
Smoking is the greatest preventable cause of mortality and a significant economic burden. Even with the best available treatments, most smokers relapse within days or weeks after a quit attempt. Nicotine replacement therapy, the most widely used pharmacotherapy, yields end of treatment quit rates of <25% suggesting that managing nicotine withdrawal is not sufficient. To improve quit rates significantly, a more refined mechanistic understanding is needed. Neuroimaging can identify mechanisms underlying behavior change beyond self-report and behavioral measures. Functional magnetic resonance imaging (fMRI) studies show that brief (e.g., 24 hr.) abstinence from smoking produces working memory deficits associated with reduced neural activity in cognitive control circuits. This study will examine how abstinence-induced brain changes contribute to clinical outcomes in treatment-seeking smokers. Using a validated fMRI abstinence challenge paradigm, 200 treatment-seeking smokers will complete two 1-hour pre-treatment fMRI scans: after smoking satiety and after 24 hours of confirmed abstinence. Approximately 50% of participants will complete the smoking session first, followed by the absence session, and the remainder will complete the opposite order (counterbalanced). The investigators will examine brain responses during the performance of tasks probing working memory. Participants will then set a target quit date, receive smoking cessation counseling, and be monitored for 6 months to assess time to relapse using a validated smoking relapse protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Standard smoking cessation counseling | Other | Behavioral: Standard smoking cessation counselingParticipants will receive a standard treatment program consisting of smoking cessation counseling. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Treatment-seeking smokers between the ages of 18 and 65, reporting consumption of at least 5 cigarettes per day for at least the past 6 months;
- Planning to live in the area for at least the next 3 months;
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the combined consent and HIPAA form;
- Able to communicate fluently in English (speaking, writing, and reading).
Key exclusion criteria (46 listed)
- Subjects who present and/or self-report with the following criteria at any point during study participation will not be eligible to participate in the study:
- Use of chewing tobacco or snuff or cigars;
- Current enrollment or plans to enroll in another smoking cessation program or research study in the next 3 months;
- Current or anticipated (within the next 3 months) use of smoking cessation medications or nicotine replacement therapy (NRT);
- A baseline carbon monoxide (CO) reading less than or equal to 8ppm.
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 |
|---|---|---|
| Standard smoking cessation counselingParticipants will discuss reasons for quitting, the model of smoking as a learned habit, triggers for smoking, and trigger management; receive brief training in how to manage withdrawal symptoms and relapse prevention counseling and receive the NCI Clearing the Air self-help smoking cessation booklet. The target quit date (TQD) session will be scheduled to occur up to 2 weeks following the pre-quit session. Participants will then meet with a smoking cessation counselor for a 15 minute booster counseling session. During the first week following TQD there will be two monitoring visits to closely monitor abstinence. Weekly thereafter for four weeks, participants will attend a brief booster counseling session. | Behavioural | Standard smoking cessation counseling |
Primary outcome
Days to Relapse
Time frame: 6 months after target quit date
The primary outcome will be the number of days to relapse following the target quit date. Relapse will be confirmed using a conventional SRNT guideline criterion of either a positive biochemical verification of smoking or 7 consecutive days of smoking based on self-report (it is very unlikely that a subject would meet the latter criterion without also meeting the former, given the long half-life of cotinine). The days to relapse will be based upon time from target quit date to the first day of the relapse period. Self-reported daily smoking data will be collected using a validated timeline follow-back method. Self-reported abstinence will be biochemically verified on a weekly basis using urine cotinine (<100ng/ml) and a CO reading of ≤5PPM. Drop-outs will be considered relapsers following the last date of abstinence data provided.
1 secondary outcome
Brain Activation (BOLD Percent Signal Change)
Time frame: 24 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30806013Allenby C, Falcone M, Wileyto EP, Cao W, Bernardo L, Ashare RL, Janes A, Loughead J, Lerman C. Neural cue reactivity during acute abstinence predicts short-term smoking relapse. Addict Biol. 2020 Mar;25(2):e12733. doi: 10.1111/adb.12733. Epub 2019 Feb 25.
- Click here for more information about this study: Neural mechanisms associated with risk of smoking relapseLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
James Loughead, Ph.D. principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Standard smoking cessation counseling in people with Nicotine Addiction, run by University of Pennsylvania at 1 site in United States.
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 5 inclusion and 46 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 5 Mar 2025. 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. 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 5 Mar 2025). 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?
Days to Relapse (time frame: 6 months after target quit date). 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 NCT02837510, which also lists 1 linked publication.
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 5 Mar 2025.