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Protocol Details

Neuroplasticity Following Theta-Burst Stimulation in Cocaine Use Disorder

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

17-DA-N002

Sponsoring Institute

National Institute on Drug Abuse (NIDA)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 22 Years
Max Age: 60 Years

Referral Letter Required

No

Population Exclusion(s)

Non-English Speaking;
Pregnant Women;
Adults who are or may become unable to consent;
Children

Keywords

Non-Invasive Brain Stimulation;
Functional Magnetic Resonance Imaging (fMRI);
intermittent theta burst stimulation (iTBS);
Transcranial Magnetic Stimulation (TMS)

Recruitment Keyword(s)

None

Condition(s)

Cocaine Use Disorder;
Cocaine Dependence

Investigational Drug(s)

None

Investigational Device(s)

MagVenture MagPro 100 with MagOption

Intervention(s)

Device: Transcranial magnetic stimulation (TMS)

Supporting Site

National Institute on Drug Abuse

The goal of this clinical trial is to assess the tolerability of an accelerated intermittent theta burst stimulation (iTBS, a form of transcranial magnetic stimulation) intervention in participants with cocaine use disorder and then to determine if the intervention changes brain circuits related to cocaine use disorder and whether these changes relate to clinical outcomes. The main questions it aims to answer are:

-Can individuals with cocaine use disorder tolerate accelerated iTBS (3 treatments per day for 10 days) (Pilot study)?

-Does iTBS (compared to sham iTBS) alter brain circuits related to cocaine use disorder (Expanded feasibility study)? Researchers will compare individuals with cocaine use disorder to those without cocaine use disorder to identify differences at baseline, compare effects of the first day of iTBS treatment, and see if changes after treatment align brain circuits in those with cocaine use disorder more closely to patterns seen in those without cocaine use disorder.

Participants will:

-Undergo 10 days of iTBS treatment and two follow-up visits (1 week and 4 weeks after treatment) and complete questionnaires throughout to assess tolerability and drug use (Pilot study).

-Participants with cocaine use disorder will complete a characterization phase with questionnaires, two fMRI scans and a trial session of iTBS (sham or active) before the treatment phase (Expanded feasibility study).

-Participants with cocaine use disorder will complete a treatment phase with questionnaires, urine drug testing, two fMRI scans before and after the first day of treatment, ten days with three iTBS treatments (sham or active) each day (Expanded feasibility study).

-Participants with cocaine use disorder will complete a follow-up phase with contingency management for 11 weeks, follow-up fMRI scans 2 weeks and three months after the end of iTBS treatment and three monthly follow-up visits with urine drug testing and questionnaires after completion of the contingency management phase.

-Participants without cocaine use disorder will complete the same characterization phase as those with cocaine use disorder but will not receive a full treatment course of iTBS. Instead, they will complete the first treatment day twice, once with active and once with sham iTBS.

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Eligibility

INCLUSION CRITERIA - PILOT PHASE: P1:

1. Be able to give valid informed consent.

2. Be 18 - 60 years of age.

3. Right-handed.

4. Be in good health.

5. Absence of a specific learning disability, ADHD or cognitive impairment

6. Participants will meet DSM-5 criteria for current moderate to severe substance (i.e., cocaine) use disorder, without a period of continuous abstinence lasting a one-month period over the last year, other than in a controlled environment.

EXCLUSION CRITERIA - PILOT PHASE: P1:

1. History of any neurological disorder 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 one month.

2. Current DSM-5 moderate-severe substance use disorder on a substance other than cocaine, nicotine, marijuana, or opiates (provided they are currently stable on Suboxone) or meeting withdrawal criteria for alcohol or a sedative/hypnotic/anxiolytic, or tolerance criteria in an individual using 3 or more days/week, regardless of diagnosis. Individuals will be considered stable on Suboxone if they have been on a stable dose for at least 2-weeks prior to consenting to 17-DA-N002 and have provided at least 3 urine specimens negative for illicit opioids over the same 2-week period (10 business days) with at least one test collected within two business days of the start of the period, one collected within three business days of the end of the period and one collected at least two days from either of the other two specimens. Urine results may be gathered at NIDA as part of screening or be provided by the Suboxone prescriber. Communication between the Suboxone provider and the MAI (or covering Staff Clinician) will be ongoing to establish continued illicit opioid abstinence between participant clearance and consent to 17-DA-N002. Individuals must be receiving their Suboxone as take-home doses from an external (i.e., non-NIDA-IRP) provider.

3. First-degree family history of any neurological disorder with a potentially hereditary basis, including migraines, epilepsy, or multiple sclerosis.

4. Cardiac pacemakers, neural stimulators, implantable defibrillator, implanted medication pumps, intracardiac lines, or acute, unstable cardiac disease, with intracranial implants (e.g. aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object in the body that precludes iTBS administration.

5. Noise-induced hearing loss or tinnitus.

6. Current use (any use in the past 4 weeks, daily use for more than a week within past 6 months) of any investigational drug or of any medications with psychotropic (e.g., benzodiazepines), anti or pro-convulsive action, or anti-coagulants. This will be determined at the discretion of the MAI.

7. Lifetime history of schizophrenia, bipolar disorder, mania, or hypomania.

8. 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.

9. Pregnant or lactating women or women with reproductive potential who engage in heterosexual sex that may lead to pregnancy and not using a medically acceptable form of contraception (such as birth control pills, condoms, or a diaphragm with spermicide).

10. 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.

INCLUSION CRITERIA - EXPANDED FEASIBILITY PHASE (EFS):

1. Be able to give valid informed consent.

2. Agree to also participate in study 10DAN457, where characterization information is gathered and shared with this protocol.

3. Be 22 - 60 years of age.

4. Right-handed.

5. Be in good health.

6. Absence of a specific learning disability, ADHD or cognitive impairment

7. CD Participants, and not HC participants, will meet DSM-5 criteria for current moderate to severe substance (i.e., cocaine) use disorder, without a period of continuous abstinence lasting a one-month period over the last year, other than in a controlled environment and currently seeking treatment. They will be using at least once a week in the month prior to enrollment.

8. Treatment seeking CD participants

9. MRI compatible

EXCLUSION -EFS:

1. History of any neurological disorder 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 one month.

2. Current DSM-5 moderate-severe substance use disorder on a substance other than cocaine, nicotine, marijuana, or opiates (provided they are currently stable on a medication assisted treatment) or meeting withdrawal criteria for a sedative/hypnotic/anxiolytic, or tolerance criteria in an individual using 3 or more days/week, regardless of diagnosis. Individuals will be considered stable on a maintenance medication if they have been on a stable dose for at least 2-weeks prior to consenting to 17-DA-N002 and have provided at least 3 urine specimens negative for illicit opioids over the same 2-week period (10 business days) with at least one test collected within two business days of the start of the period, one collected within three business days of the end of the period and one collected at least two days from either of the other two specimens. Urine results may be gathered at NIDA as part of screening or be provided by the buprenorphine maintenance prescriber. Communication between the maintenance provider and the MAI (or covering Staff Clinician) will be ongoing to establish continued illicit opioid abstinence between participant clearance and consent to 17-DA-N002.

3. HC participants will not currently meet DSM-5 criteria for moderate to severe substance use disorder (excluding nicotine), and in the past, will not meet DSM-5 criteria for moderate to severe substance use disorder for cannabis or alcohol in the past 5 years or ever for other illicit substances. HC will not meet current withdrawal criteria for alcohol or sedative/hypnotics/anxiolytics, or tolerance criteria in an individual using 3 or more days/week. Urine toxicology positive for any illicit substance inconsistent with history given will also be exclusionary.

4. First-degree family history of any form of epilepsy with a potentially hereditary basis .

5. Cardiac pacemakers, neural stimulators, implantable defibrillator, implanted medication pumps, intracardiac lines, or acute, unstable cardiac disease, with intracranial implants (e.g. aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object in the body that precludes iTBS administration.

6. Noise-induced hearing loss or tinnitus.

7. Current use (any use in the past 4 weeks, daily use for more than a week within past 6 months) of any investigational drug or of any medications with psychotropic (e.g., benzodiazepines), anti or pro-convulsive action, or anti-coagulants. This will be determined at the discretion of the MAI.

8. Lifetime history of schizophrenia, bipolar disorder, mania, or hypomania.

9. Pregnant women or women with reproductive potential who engage in heterosexual sex that may lead to pregnancy and not using a medically acceptable form of contraception (such as birth control pills, condoms, or a diaphragm with spermicide).

10. Participation in any NIBS session less than two weeks prior to admission. No NIBS exposure for treatment purposes in the last 6 months.

11. Non-English speaking.


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Citations:

Steele VR, Maxwell AM, Ross TJ, Stein EA, Salmeron BJ. Accelerated Intermittent Theta-Burst Stimulation as a Treatment for Cocaine Use Disorder: A Proof-of-Concept Study. Front Neurosci. 2019 Oct 30;13:1147. doi: 10.3389/fnins.2019.01147. PMID: 31736689; PMCID: PMC6831547.

Steele VR, Maxwell AM, Ross TJ, Moussawi K, Abulseoud OO, Stein EA, Salmeron BJ. Report of transient events in a cocaine-dependent volunteer who received iTBS. Brain Stimul. 2018 May-Jun;11(3):631-633. doi: 10.1016/j.brs.2018.01.004. Epub 2018 Jan 31. PMID: 29429954.

Steele VR, Rotenberg A, Philip NS, Hallett M, Stein EA, Salmeron BJ. Case report: Tremor in the placebo condition of a blinded clinical trial of intermittent theta-burst stimulation for cocaine use disorder. Front Psychiatry. 2024 Jul 9;15:1391771. doi: 10.3389/fpsyt.2024.1391771. PMID: 39045554; PMCID: PMC11263940.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Yihong Yang, Ph.D.
National Institute on Drug Abuse (NIDA)
NIDA IRP Office of Human Subjects Research
251 Bayview Blvd, Suite 200
Baltimore, Maryland 21224
(667) 312-5364
yihongyang@intra.nida.nih.gov

NIDA IRP Screening Team
National Institute on Drug Abuse (NIDA)

(800) 535-8254
researchstudies@nida.nih.gov

NIDA IRP Screening Team

(800) 535-8254
researchstudies@nida.nih.gov

Clinical Trials Number:

NCT02927236

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