Theta-Burst Stimulation as a Treatment for Reducing Cocaine Use

NCT ID: NCT02927236

Last Updated: 2025-02-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-13
• Study Completion Date: 2023-10-30

Brief Summary

Objective: 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).

Detailed Description

Background and objective: 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.

Study Population: Participants age 18 - 60 years of age (pilot study) and participants age 22 - 60 (Expanded Feasibility Study)

Study Design:

• Participants with cocaine dependence will receive open label iTBS in the pilot study
• Participants with cocaine dependence will receive active or sham iTBS in double blinded experiment in the Expanded Feasibility Study (EFS)
• Healthy Participants will complete the first treatment day twice and receive both active and sham iTBS treatment over two visits with at least five days between visits in a double blinded experiment

Conditions

Cocaine Use Disorder; Cocaine Dependence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Pilot Group

Participants with cocaine dependence receive open label three daily intermittent Theta-Burst Stimulation (iTBS) sessions with an inter-administration interval of at least 60-minutes between sessions for up to 10 days.

Group Type: EXPERIMENTAL

Transcranial magnetic stimulation (TMS)

Intervention Type: DEVICE

Theta burst stimulation is a type of TMS.To administer the iTBS treatment, a MagVenture MagPro 100 with MagOption (MagVenture Inc, Alpharetta, GA) machine equipped with a figure-8 active/sham coil will be used.

Expanded Feasibility Study (EFS): Cocaine - Active Group

Participants with cocaine dependence receive three active daily intermittent Theta-Burst Stimulation (iTBS) sessions with an inter-administration interval of at least 60-minutes between sessions in a double-blind experiment for up to 10 days and fMRI brain scans.

Group Type: EXPERIMENTAL

Transcranial magnetic stimulation (TMS)

Intervention Type: DEVICE

Theta burst stimulation is a type of TMS.To administer the iTBS treatment, a MagVenture MagPro 100 with MagOption (MagVenture Inc, Alpharetta, GA) machine equipped with a figure-8 active/sham coil will be used.

Expanded Feasibility Study (EFS): Cocaine - Sham Group

Participants with cocaine dependence receive three sham daily intermittent Theta-Burst Stimulation (iTBS) sessions with an inter-administration interval of at least 60-minutes between sessions in a double-blind experiment for up to 10 days and fMRI brain scans.

Group Type: SHAM_COMPARATOR

Transcranial magnetic stimulation (TMS)

Intervention Type: DEVICE

Theta burst stimulation is a type of TMS.To administer the iTBS treatment, a MagVenture MagPro 100 with MagOption (MagVenture Inc, Alpharetta, GA) machine equipped with a figure-8 active/sham coil will be used.

Expanded Feasibility Study (EFS): Healthy Control

Healthy participants without cocaine dependence receive three active daily intermittent Theta-Burst Stimulation (iTBS) sessions with an inter-administration interval of at least 60-minutes between sessions in a double-blind experiment in one day and three sham daily iTBS sessions with an inter-administration interval of at least 60-minutes between sessions in a double-blind experiment in one day with at least five days between the active and sham treatment.

Group Type: OTHER

Transcranial magnetic stimulation (TMS)

Intervention Type: DEVICE

Theta burst stimulation is a type of TMS.To administer the iTBS treatment, a MagVenture MagPro 100 with MagOption (MagVenture Inc, Alpharetta, GA) machine equipped with a figure-8 active/sham coil will be used.

Interventions

Transcranial magnetic stimulation (TMS)

Theta burst stimulation is a type of TMS.To administer the iTBS treatment, a MagVenture MagPro 100 with MagOption (MagVenture Inc, Alpharetta, GA) machine equipped with a figure-8 active/sham coil will be used.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

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, attention deficit hyperactivity disorder (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.

1. Be able to give valid informed consent.

2. Agree to also participate in study 10-DA-N457, 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. Cocaine dependent (CD) participants, and not healthy control (HC) participants, will meet Diagnostic and Statistical Manual (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.

Exclusion Criteria

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 National Institute on Drug Abuse (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.

• Minimum Eligible Age: 22 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yihong Yang, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

National Institute on Drug Abuse (NIDA)

Locations

National Institute on Drug Abuse

Baltimore, Maryland, United States

Countries

United States

References

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. No abstract available.

Reference Type: BACKGROUND

PMID: 29429954 (View on PubMed)

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. eCollection 2024.

Reference Type: BACKGROUND

PMID: 39045554 (View on PubMed)

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. eCollection 2019.

Reference Type: RESULT

PMID: 31736689 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

17-DA-N002

Identifier Type: OTHER

Identifier Source: secondary_id

999917002

Identifier Type: -

Identifier Source: org_study_id