Nicotine DependenceNCT03707600
State and Trait Mediated Response to TMS in Substance Use Disorder
A study testing TMS in people with Nicotine Dependence, run by National Institute on Drug Abuse (NIDA) at 1 site in United States.
Trial summary
OBJECTIVES: The current protocol seeks to develop brain-based intermediate phenotypes of response to transcranial magnetic stimulation (TMS) in chronic substance use disorder (SUD). Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Nicotine Dependence
- What is being tested?
- TMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Sep 2018to 8 Jun 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- All participants must:
- Be between the ages of 18-60. Justification: Many neural processes change with age, and these changes could introduce unwanted variability in both behavioral and MRI signals. In addition, the risk of difficult-to-detect medical abnormalities such as silent cerebral infarcts increase with age. Assessment tools: History. Government- issued forms of identification (e.g. driver s license, birth certificate) will be required when participant appears to be out of age range.
- Be in good health. Justification: Many illnesses may alter fMRI signals as well as cognitive processes and neural functioning. Assessment tools: Medical Assessment, Medical History and Physical Examination. Medical assessments include: Vital Signs, EKG, oral HIV test, height/weight measurements, urinalysis and blood sample. Tests on the blood sample include CBC, complete metabolic profile, TSH, ESR, STS and HIV (if needed to confirm a positive salivary test for HIV). The following individual laboratory results will independently disqualify individuals: Cholesterol greater than 250 mg/dl, Hemoglobin less than 10.5 g/dl, WBC less than 2400/ (Micro)l, LFTs less than 3 times upper normal, HCG positive, Casual serum glucose less than 200 mg/dl, Urine protein less than 1+. The MAI will retain discretion to exclude at less extreme values, depending on the clinical presentation. (Serum glucose over 140 mg/dl will be followed up with a fasting serum glucose assessment. Those with fasting glucose below 100 mg/dl may be considered for the protocol. Others will be rejected and referred for work-up.) Liver function will be evaluated with aspartate aminotransferase (AST) and alanine transaminase (ALT). A greater than 3 times upper normal limit for AST or ALT will disqualify individuals. MAI will make the final judgment on any questionable lab results.
- Be right-handed. Justification: Using right-handed individuals will reduce variability in BOLD MRI data. Assessment tool: Edinburgh Handedness Inventory.
- Be able to abstain from alcohol and other substances 24hrs and caffeine for 12 hours before each of the imaging sessions. Justification: Alcohol and caffeine (among other substances) modulate neural functioning in a way that would complicate data interpretation. Assessment tools: Self-report, urine drug screen and breathalyzer.
- For smoker group, must have a urine cotinine level of greater than 4 as measured by a semi-quantitative in vitro diagnostic (e.g., NicAlert) and have been smoking a regular combustible tobacco product consistently for at least one year. Based on the correlation between self-reported cpd/FTND and urine cotinine levels, a single inclusion criterion will be easier to manage and provide adequate characterization of dependent smokers. Urine cotinine level provides a biomarker that does not rely on self-report/memory. Quit attempts will be assessed via clinical interview and judgment. Justification: The present protocol is interested in neurobiological mechanisms that underlie nicotine dependence-induced plasticity, and is thus contingent on the presence of nicotine dependence. Assessment tools: Self-report, NicAlert of 4 or higher (or other nicotine/cotinine lab test equivalent to 200ng/ml cotinine concentration)
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- For the smoker group, must be willing to attempt an acute abstinence period lasting approximately 48 hours on 2 separate occasions. Justification: We aim to look at the response to stimulation in both drug sated and abstinent states in smokers. Assessment tool: Self-report.
- For the non-smoking control group, less than 20 cigarettes lifetime, no cigarette or other nicotine product in past year and no history of daily use of any other nicotine products for > 2 weeks. Justification: Minimal cigarette exposure in the control group is required to assess differences between healthy control and the smoker groups. Assessment tools: Self-report, NicAlert of less than or equal 2, CO less than 6 or MAI discretion if there is a reasonable planation for high CO exposure.
- Participants must:
- Be Right-handed.
- Justification: Differences in hemispheric dominance could confound iTBS administration and MRI measurements.
- Screening tool: Self-report.
- Be in good health.
- Justification: Many illnesses may increase likelihood of TMS ...
Who cannot join
- Current or personal history of cerebrovascular or neurological illnesses including, but not limited to, seizure disorders, frequent migraines or on prophylaxis, multiple sclerosis, movement disorders, history of significant head trauma, or CNS tumor. Current or personal history of any neurological disorders that would increase seizure risk from iTBS such as stroke, brain lesions, previous neurosurgery, any history of seizure or fainting episode of unknown cause, or head trauma resulting in loss of consciousness, lasting over 30 minutes or with sequela lasting longer than three months, regardless of loss of consciousness. Justification: Cerebrovascular and neurological conditions may alter blood flow, CNS function, the fMRI signal and other autonomic signals. Additionally, neurological disorders such as stroke, vascular lesions or head trauma can lower the seizure threshold and are therefore contra-indications for iTBS. Fainting episodes or syncope of unknown cause could indicate an undiagnosed condition associated with seizures. Assessment tools: TMS Safety Screen and Medical History and Physical Exam. The MAI who will also retain discretion to exclude based on a history of neurological illness that may compromise data integrity.
- First-degree family history of any neurological disorder with a potentially hereditary basis, including migraines, epilepsy, or multiple sclerosis. Justification: Neurological disorders can lower the seizure threshold and are therefore contra-indications for iTBS. First -degree family history of certain neurological disorder with a hereditary component increases the risk of the participant having an undiagnosed conditi n that is associated with lowered seizure threshold. Assessment tools: TMS Safety Screen and Medical History.
- Implantable defibrillator, implanted medication pumps, cardiac pacemaker, neurostimulator, some artificial joints, metal pins, surgical clips, intracardiac lines, or acute unstable cardiac disease with intracranial implants (e.g. aneurysm clips, shunts, stimulators, cochlear implants or electrodes) or any other implant or metal object in the body that precludes MRI scanning or iTBS administrations. Justification: certain metal in the body is a contra-indication for MRI scanning and iTBS administration, which involves exposure to a relatively strong static magnetic field that can move magnetic material not securely bound and rapidly alternating magnetic fields that can generate heat and current in metal contained in the body. Assessment tools: TMS Safety Screen, MRI Safety Screen and Medical History.
- Are not suitable to undergo an fMRI experiment due to body morphology or claustrophobia. Justification: MR scanning is one of the primary measurement tools used in the protocol. Assessment tools: MRI Safety Screen, Medical History. Prospective participants will be questioned about symptoms of claustrophobia and may be placed in the mock scanner during screening to assess for possible difficulty tolerating the confinement of the scanner and for ability to fit into the scanner. Noise-induced hearing loss or tinnitus. Justification: individuals with noise-induced hearing problems may be particularly vulnerable to the acoustic noise generated by iTBS equipment and MRI (even with the use of sound attenuation ear plugs). Assessment tools: TMS Safety Screen, MRI Safety Screen, Medical History.
- Current use (any use in the past 4 weeks, daily use for more than a week within the past 6 months) of any substances (excluding alcohol, see criteria 9), investigational drug or of any medications with psychotropic, anti- or pro-convulsive action, or anti coagulants. This will be determined at the discretion of the MAI. Justification: the use of certain medications or drugs can lower seizure threshold during use or withdrawal and is therefore contra-indicated for iTBS. Assessment tools: Medical History, urine toxicology analysis for the presence of a broad range of prescription and non-prescription drugs. Lifetime history of schizophrenia, bipolar disorder, mania, or hypomania. Justification: The population of interest here is a healthy population with no psychiatric disorders other than tobacco use disorders. In participants with bipolar disorder, mania or hypomania, there is a small chance that iTBS can trigger (hypo)manic symptoms. Assessment tools: M.I.N.I. Potential diagnoses will be further evaluated by a counselor.
- Current major psychiatric disorders to include, but not limited to, mood, anxiety, psychotic disorders, or substance-induced psychiatric disorders, or any current suicidal ideations or currently under antidepressant or antipsychotic medication treatment. 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. Assessment tools: M.I.N.I., Beck Depression Inventory, Beck Anxiety Inventory, Adult ADHD Self-Report Scales and clinical terview confirmation by clinician.
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- Meet current DSM-5 criteria for moderate to severe substance use disorder, for alcohol or any drug (except nicotine for the smoker group). Past substance use disorder (SUD) is acceptable based on MAI determination. Those with past SUD of substances other than alcohol or marijuana may not have any current use (past 6 months) of the substance on which they were dependent. Individuals with past SUD of either alcohol or marijuana who report current use of the previously dependent substance may be included provided they do not currently meet withdrawal criteria. Justification: SUD of other substances (drugs or alcohol) may result in unique CNS deficits that could confound results and introduce excessive variance. Assessment tools: The Mini International Neuropsychiatric Interview (M.I.N.I) and clinical SUD assessment, Drug Use Survey, Addiction Severity Index. A positive drug test for marijuana will not be exclusionary as long as participants, based on self- report, have not used in the 24hrs preceding the imaging visits. In the event of a positive drug test for marijuana, self-reports of current marijuana use will be used to differentiate intermittent/infrequent from chronic/frequent users.
- History of myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, mitral valve prolapse, or any heart condition currently under medical care. Justification: the risk of iTBS for individuals with a heart condition is unknown, further such conditions may alter blood flow, the fMRI signal and other autonomic signals. These conditions are also likely to add considerable additional variability to the data. Assessment tools: physical assessment, EKG, medical history.
- Women who are pregnant, sexually active and not using an acceptable form of birth control. Justification: study procedures used in the current protocol (MRI, iTBS) may complicate pregnancy. Assessment tools: Urine and/or serum pregnancy tests, and clinical interview. Urine pregnancy tests will also be conducted at the beginning of each imaging visit.
- Participation in any NIBS session (excluding the current protocol) less than two weeks ago. No NIBS exposure for treatment purposes in the last 6 months. Justification: in order to avoid possible carry-over effects from previous exposure to NIBS prior to participation in the proposed intervention, we will not enroll participants who have received any NIBS in the two weeks preceding enrollment or treatment with NIBS modality with the last 6 months preceding enrollment. Assessment tools: TMS safety screen.
- 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: Medical History and Wechsler Abbreviated Scale of Intelligence (WASI). IQ estimate must be 80 or over.
- Have coagulopathies, history of, current superficial, or deep vein thrombosis, 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 two hours. Therefore, conditions that would make that difficult (e.g. chronic back pain, significant scoliosis) or dangerous (e.g. familial hypercoagulability syndrome, history of thrombosis) will be exclusionary. Assessment tools: History and physical examination by a qualified IRP clinician, supplemented with a trial of lying in the mock scanner to ssess comfort issues.
- Regularly use any prescription (e.g., antidepressants, benzodiazepines, antipsychotics, anticonvulsants, barbiturates), over-the-counter (e.g., cold medicine) or herbal medication (e.g., Kava, Gingko biloba, St. John s wort) that may alter CNS function, cardiovascular function, or 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 tools: History and comprehensive urine drug screening to detect antidepressants, benzodiazepines, antipsychotics, anticonvulsants, and barbiturates.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute on Drug Abuse
Baltimore, Maryland, 21224
About this study
OBJECTIVES: The current protocol seeks to develop brain-based intermediate phenotypes of response to transcranial magnetic stimulation (TMS) in chronic substance use disorder (SUD). To date the field has relied on subjective reports, behavioral performance, and long-term clinical outcomes as primary measures of TMS efficacy. While certainly ecologically valid, these observable behaviors lack the sensitivity necessary to fully quantify the effects (or lack thereof) across both individual participants and TMS intervention protocols.
This proposed within-subjects design seeks to leverage differences in metaplasticity that is, the context in which stimulation occurs-by studying the response to stimulation in both sated and abstinent states. It is predicted these state manipulations will potentiate response to TMS. When a disruptive allostatic load like chronic nicotine exposure or acute abstinence is placed on the brain, the underlying network becomes less stable and thus more susceptible to TMS intervention. For SUD in general and tobacco use disorder (TUD) in particular, this state dependence of TMS response is a potentially valuable tool to improve a given intervention s clinical efficacy.
Read more
STUDY POPULATION: Physically and psychiatrically healthy smokers will be recruited. A comparison group of non-smokers will be concurrently enrolled. We estimate we will require n=51/group of completers to have sufficient power to develop the intermediate phenotypes of TMS.
DESIGN: The protocol is a two group, between/within subject, fully counterbalanced design. The between-subjects factor is GROUP (smoker/non-smoker) and the within-subjects factor for each GROUP is TMS CONDITION (active/sham). Additionally, and for the smoker group, nicotine STATE (sated/abstinent) is a nested within-subjects factor. Each group will receive single sessions of active and sham intermittent theta burst stimulation to left dorsal lateral prefrontal cortex, followed immediately by an MRI scan to characterize the acute neurobiological response to stimulation. Smokers will repeat these procedures both during smoking satiety and following an ~48-hour period nicotine abstinence.
OUTCOMES PARAMETERS: In addition to subjective and behavioral task performance changes associated with TMS intervention, changes in MRI BOLD signal will be used to characterize the neurobiological response to TMS intervention across groups and states. Taken together, the development of brain-based markers of TMS response may thus improve both our mechanistic understanding of the causal dysfunctions of TUD as well as the potential efficacy of these interventions longer term to address the relevant clinical characteristics of the disease and ultimately improve treatment outcomes.
Read the detailed description
OBJECTIVES: The current protocol seeks to develop brain-based intermediate phenotypes of response to transcranial magnetic stimulation (TMS) in chronic substance use disorder (SUD). To date the field has relied on subjective reports, behavioral performance, and long-term clinical outcomes as primary measures of TMS efficacy. While certainly ecologically valid, these observable behaviors lack the sensitivity necessary to fully quantify the effects (or lack thereof) across both individual participants and TMS intervention protocols.
This proposed within-subjects design seeks to leverage differences in metaplasticity that is, the context in which stimulation occurs-by studying the response to stimulation in both sated and abstinent states. It is predicted these state manipulations will potentiate response to TMS. When a disruptive allostatic load like chronic nicotine exposure or acute abstinence is placed on the brain, the underlying network becomes less stable and thus more susceptible to TMS intervention. For SUD in general and tobacco use disorder (TUD) in particular, this state dependence of TMS response is a potentially valuable tool to improve a given intervention s clinical efficacy.
STUDY POPULATION: Physically and psychiatrically healthy smokers will be recruited. A comparison group of non-smokers will be concurrently enrolled. We estimate we will require n=51/group of completers to have sufficient power to develop the intermediate phenotypes of TMS.
DESIGN: The protocol is a two group, between/within subject, fully counterbalanced design. The between-subjects factor is GROUP (smoker/non-smoker) and the within-subjects factor for each GROUP is TMS CONDITION (active/sham). Additionally, and for the smoker group, nicotine STATE (sated/abstinent) is a nested within-subjects factor. Each group will receive single sessions of active and sham intermittent theta burst stimulation to left dorsal lateral prefrontal cortex, followed immediately by an MRI scan to characterize the acute neurobiological response to stimulation. Smokers will repeat these procedures both during smoking satiety and following an ~48-hour period nicotine abstinence.
OUTCOMES PARAMETERS: In addition to subjective and behavioral task performance changes associated with TMS intervention, changes in MRI BOLD signal will be used to characterize the neurobiological response to TMS intervention across groups and states. Taken together, the development of brain-based markers of TMS response may thus improve both our mechanistic understanding of the causal dysfunctions of TUD as well as the potential efficacy of these interventions longer term to address the relevant clinical characteristics of the disease and ultimately improve treatment outcomes.
- Conditions
- Nicotine Dependence
- Being tested
- TMS
- Keywords
- Nicotine Abstinence, Metaplasticity, Nicotine, Functional Magnetic Resonance Imaging (fMRI), Transcranial Magnetic Stimulation (TMS)
- 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.
TMSDevice
MagVenture MagPro 100 with MagOption (MagVenture Inc, Alpharetta, GA) machine equipped with a figure-8 coil.
| Study group | Role | What they receive |
|---|---|---|
| Sham | Sham comparator | The sham coil setting is designed to mimic the auditory artifact and scalp sensations evoked by the real coil without stimulating the brain. Receives: Device: TMS |
| TMS | Active comparator | Active TMS Receives: Device: TMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Subjective and behavioral task report and changes in MRI BOLD signal
changes in MRI BOLD signal
Measured: Each TMS/MRI visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2018
- Study start27 Sep 2018
- Primary completion8 Jun 2020
- Study completion8 Jun 2020
Why it stopped: PI closing his lab
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Drug Abuse (NIDA)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Elliot Stein, Ph.D., Principal investigator, National Institute on Drug Abuse (NIDA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03707600
- Sponsor's protocol ID
- 999918148
- Other IDs
- 18-DA-N148
- Status last verified
- Oct 2019
- First submitted
- 11 Oct 2018
- Last updated
- 16 Jun 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- State and Trait Mediated Response to TMS in Substance Use Disorder
- ClinicalTrials.gov ID
- NCT03707600
- Acronym / sponsor ID
- 999918148
- Conditions
- Nicotine Dependence
- Keywords
- Nicotine Abstinence, Metaplasticity, Nicotine, Functional Magnetic Resonance Imaging (fMRI), Transcranial Magnetic Stimulation (TMS)
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: PI closing his lab
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Institute on Drug Abuse (NIDA)US National Institutes of Health
- Study start
- 27 Sep 2018 (actual)
- Primary completion
- 8 Jun 2020 (actual)
- Study completion
- 8 Jun 2020 (actual)
- First posted
- 16 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
OBJECTIVES: The current protocol seeks to develop brain-based intermediate phenotypes of response to transcranial magnetic stimulation (TMS) in chronic substance use disorder (SUD). To date the field has relied on subjective reports, behavioral performance, and long-term clinical outcomes as primary measures of TMS efficacy. While certainly ecologically valid, these observable behaviors lack the sensitivity necessary to fully quantify the effects (or lack thereof) across both individual participants and TMS intervention protocols.
This proposed within-subjects design seeks to leverage differences in metaplasticity that is, the context in which stimulation occurs-by studying the response to stimulation in both sated and abstinent states. It is predicted these state manipulations will potentiate response to TMS. When a disruptive allostatic load like chronic nicotine exposure or acute abstinence is placed on the brain, the underlying network becomes less stable and thus more susceptible to TMS intervention. For SUD in general and tobacco use disorder (TUD) in particular, this state dependence of TMS response is a potentially valuable tool to improve a given intervention s clinical efficacy.
STUDY POPULATION: Physically and psychiatrically healthy smokers will be recruited. A comparison group of non-smokers will be concurrently enrolled. We estimate we will require n=51/group of completers to have sufficient power to develop the intermediate phenotypes of TMS.
DESIGN: The protocol is a two group, between/within subject, fully counterbalanced design. The between-subjects factor is GROUP (smoker/non-smoker) and the within-subjects factor for each GROUP is TMS CONDITION (active/sham). Additionally, and for the smoker group, nicotine STATE (sated/abstinent) is a nested within-subjects factor. Each group will receive single sessions of active and sham intermittent theta burst stimulation to left dorsal lateral prefrontal cortex, followed immediately by an MRI scan to characterize the acute neurobiological response to stimulation. Smokers will repeat these procedures both during smoking satiety and following an ~48-hour period nicotine abstinence.
OUTCOMES PARAMETERS: In addition to subjective and behavioral task performance changes associated with TMS intervention, changes in MRI BOLD signal will be used to characterize the neurobiological response to TMS intervention across groups and states. Taken together, the development of brain-based markers of TMS response may thus improve both our mechanistic understanding of the causal dysfunctions of TUD as well as the potential efficacy of these interventions longer term to address the relevant clinical characteristics of the disease and ultimately improve treatment outcomes.
Detailed description
OBJECTIVES: The current protocol seeks to develop brain-based intermediate phenotypes of response to transcranial magnetic stimulation (TMS) in chronic substance use disorder (SUD). To date the field has relied on subjective reports, behavioral performance, and long-term clinical outcomes as primary measures of TMS efficacy. While certainly ecologically valid, these observable behaviors lack the sensitivity necessary to fully quantify the effects (or lack thereof) across both individual participants and TMS intervention protocols.
This proposed within-subjects design seeks to leverage differences in metaplasticity that is, the context in which stimulation occurs-by studying the response to stimulation in both sated and abstinent states. It is predicted these state manipulations will potentiate response to TMS. When a disruptive allostatic load like chronic nicotine exposure or acute abstinence is placed on the brain, the underlying network becomes less stable and thus more susceptible to TMS intervention. For SUD in general and tobacco use disorder (TUD) in particular, this state dependence of TMS response is a potentially valuable tool to improve a given intervention s clinical efficacy.
STUDY POPULATION: Physically and psychiatrically healthy smokers will be recruited. A comparison group of non-smokers will be concurrently enrolled. We estimate we will require n=51/group of completers to have sufficient power to develop the intermediate phenotypes of TMS.
DESIGN: The protocol is a two group, between/within subject, fully counterbalanced design. The between-subjects factor is GROUP (smoker/non-smoker) and the within-subjects factor for each GROUP is TMS CONDITION (active/sham). Additionally, and for the smoker group, nicotine STATE (sated/abstinent) is a nested within-subjects factor. Each group will receive single sessions of active and sham intermittent theta burst stimulation to left dorsal lateral prefrontal cortex, followed immediately by an MRI scan to characterize the acute neurobiological response to stimulation. Smokers will repeat these procedures both during smoking satiety and following an ~48-hour period nicotine abstinence.
OUTCOMES PARAMETERS: In addition to subjective and behavioral task performance changes associated with TMS intervention, changes in MRI BOLD signal will be used to characterize the neurobiological response to TMS intervention across groups and states. Taken together, the development of brain-based markers of TMS response may thus improve both our mechanistic understanding of the causal dysfunctions of TUD as well as the potential efficacy of these interventions longer term to address the relevant clinical characteristics of the disease and ultimately improve treatment outcomes.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sham | Sham comparator | Device: TMSThe sham coil setting is designed to mimic the auditory artifact and scalp sensations evoked by the real coil without stimulating the brain. |
| TMS | Active comparator | Device: TMSActive TMS |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- Be between the ages of 18-60. Justification: Many neural processes change with age, and these changes could introduce unwanted variability in both behavioral and MRI signals. In addition, the risk of difficult-to-detect medical abnormalities such as silent cerebral infarcts increase with age. Assessment tools: History. Government- issued forms of identification (e.g. driver s license, birth certificate) will be required when participant appears to be out of age range.
- Be in good health. Justification: Many illnesses may alter fMRI signals as well as cognitive processes and neural functioning. Assessment tools: Medical Assessment, Medical History and Physical Examination. Medical assessments include: Vital Signs, EKG, oral HIV test, height/weight measurements, urinalysis and blood sample. Tests on the blood sample include CBC, complete metabolic profile, TSH, ESR, STS and HIV (if needed to confirm a positive salivary test for HIV). The following individual laboratory results will independently disqualify individuals: Cholesterol greater than 250 mg/dl, Hemoglobin less than 10.5 g/dl, WBC less than 2400/ (Micro)l, LFTs less than 3 times upper normal, HCG positive, Casual serum glucose less than 200 mg/dl, Urine protein less than 1+. The MAI will retain discretion to exclude at less extreme values, depending on the clinical presentation. (Serum glucose over 140 mg/dl will be followed up with a fasting serum glucose assessment. Those with fasting glucose below 100 mg/dl may be considered for the protocol. Others will be rejected and referred for work-up.) Liver function will be evaluated with aspartate aminotransferase (AST) and alanine transaminase (ALT). A greater than 3 times upper normal limit for AST or ALT will disqualify individuals. MAI will make the final judgment on any questionable lab results.
- Be right-handed. Justification: Using right-handed individuals will reduce variability in BOLD MRI data. Assessment tool: Edinburgh Handedness Inventory.
- Be able to abstain from alcohol and other substances 24hrs and caffeine for 12 hours before each of the imaging sessions. Justification: Alcohol and caffeine (among other substances) modulate neural functioning in a way that would complicate data interpretation. Assessment tools: Self-report, urine drug screen and breathalyzer.
- For smoker group, must have a urine cotinine level of greater than 4 as measured by a semi-quantitative in vitro diagnostic (e.g., NicAlert) and have been smoking a regular combustible tobacco product consistently for at least one year. Based on the correlation between self-reported cpd/FTND and urine cotinine levels, a single inclusion criterion will be easier to manage and provide adequate characterization of dependent smokers. Urine cotinine level provides a biomarker that does not rely on self-report/memory. Quit attempts will be assessed via clinical interview and judgment. Justification: The present protocol is interested in neurobiological mechanisms that underlie nicotine dependence-induced plasticity, and is thus contingent on the presence of nicotine dependence. Assessment tools: Self-report, NicAlert of 4 or higher (or other nicotine/cotinine lab test equivalent to 200ng/ml cotinine concentration)
Key exclusion criteria (13 listed)
- Current or personal history of cerebrovascular or neurological illnesses including, but not limited to, seizure disorders, frequent migraines or on prophylaxis, multiple sclerosis, movement disorders, history of significant head trauma, or CNS tumor. Current or personal history of any neurological disorders that would increase seizure risk from iTBS such as stroke, brain lesions, previous neurosurgery, any history of seizure or fainting episode of unknown cause, or head trauma resulting in loss of consciousness, lasting over 30 minutes or with sequela lasting longer than three months, regardless of loss of consciousness. Justification: Cerebrovascular and neurological conditions may alter blood flow, CNS function, the fMRI signal and other autonomic signals. Additionally, neurological disorders such as stroke, vascular lesions or head trauma can lower the seizure threshold and are therefore contra-indications for iTBS. Fainting episodes or syncope of unknown cause could indicate an undiagnosed condition associated with seizures. Assessment tools: TMS Safety Screen and Medical History and Physical Exam. The MAI who will also retain discretion to exclude based on a history of neurological illness that may compromise data integrity.
- First-degree family history of any neurological disorder with a potentially hereditary basis, including migraines, epilepsy, or multiple sclerosis. Justification: Neurological disorders can lower the seizure threshold and are therefore contra-indications for iTBS. First -degree family history of certain neurological disorder with a hereditary component increases the risk of the participant having an undiagnosed conditi n that is associated with lowered seizure threshold. Assessment tools: TMS Safety Screen and Medical History.
- Implantable defibrillator, implanted medication pumps, cardiac pacemaker, neurostimulator, some artificial joints, metal pins, surgical clips, intracardiac lines, or acute unstable cardiac disease with intracranial implants (e.g. aneurysm clips, shunts, stimulators, cochlear implants or electrodes) or any other implant or metal object in the body that precludes MRI scanning or iTBS administrations. Justification: certain metal in the body is a contra-indication for MRI scanning and iTBS administration, which involves exposure to a relatively strong static magnetic field that can move magnetic material not securely bound and rapidly alternating magnetic fields that can generate heat and current in metal contained in the body. Assessment tools: TMS Safety Screen, MRI Safety Screen and Medical History.
- Are not suitable to undergo an fMRI experiment due to body morphology or claustrophobia. Justification: MR scanning is one of the primary measurement tools used in the protocol. Assessment tools: MRI Safety Screen, Medical History. Prospective participants will be questioned about symptoms of claustrophobia and may be placed in the mock scanner during screening to assess for possible difficulty tolerating the confinement of the scanner and for ability to fit into the scanner. Noise-induced hearing loss or tinnitus. Justification: individuals with noise-induced hearing problems may be particularly vulnerable to the acoustic noise generated by iTBS equipment and MRI (even with the use of sound attenuation ear plugs). Assessment tools: TMS Safety Screen, MRI Safety Screen, Medical History.
- Current use (any use in the past 4 weeks, daily use for more than a week within the past 6 months) of any substances (excluding alcohol, see criteria 9), investigational drug or of any medications with psychotropic, anti- or pro-convulsive action, or anti coagulants. This will be determined at the discretion of the MAI. Justification: the use of certain medications or drugs can lower seizure threshold during use or withdrawal and is therefore contra-indicated for iTBS. Assessment tools: Medical History, urine toxicology analysis for the presence of a broad range of prescription and non-prescription drugs. Lifetime history of schizophrenia, bipolar disorder, mania, or hypomania. Justification: The population of interest here is a healthy population with no psychiatric disorders other than tobacco use disorders. In participants with bipolar disorder, mania or hypomania, there is a small chance that iTBS can trigger (hypo)manic symptoms. Assessment tools: M.I.N.I. Potential diagnoses will be further evaluated by a counselor.
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 |
|---|---|---|
| TMSMagVenture MagPro 100 with MagOption (MagVenture Inc, Alpharetta, GA) machine equipped with a figure-8 coil. | Device | Sham, TMS |
Primary outcome
Subjective and behavioral task report and changes in MRI BOLD signal
Time frame: Each TMS/MRI visit
changes in MRI BOLD signal
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2020.
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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.
Elliot Stein, 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?
A study testing TMS in people with Nicotine Dependence, run by National Institute on Drug Abuse (NIDA) 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 14 inclusion and 13 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: withdrawn, as of the sponsor's last update on 16 Jun 2020. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Subjective and behavioral task report and changes in MRI BOLD signal (time frame: Each TMS/MRI visit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Jun 2020.