WithdrawnNot Applicable

State and Trait Mediated Response to TMS in Substance Use Disorder

Stopped: PI closing his lab

United States0Started 2018-09-27

Plain-language 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). 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.

Who can participate

Age range

18 Years – 60 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

* INCLUSION CRITERIA (MAIN STUDY): 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 …

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Subjective and behavioral task report and changes in MRI BOLD signal

Timeframe: Each TMS/MRI visit

Trial details

NCT IDNCT03707600

SponsorNational Institute on Drug Abuse (NIDA)

Sponsor typeNIH

Study typeINTERVENTIONAL

Primary completion2020-06-08

View on ClinicalTrials.gov More Nicotine Dependence trials