Theta-Burst Stimulation as a Treatment for Reducing Cocaine Use

NCT02927236 | Terminated Results DMC FDA Device

• 2 other identifiers: 99991700217-DA-N002
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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).

Conditions

Cocaine Use Disorder; Cocaine Dependence

Keywords

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

Outcome Measures

Primary Outcomes (4)

• Number of Cocaine Dependent Participants Who Tolerated Intermittent Theta-Burst Stimulation Sessions

  Number of cocaine dependent participants who tolerated the intermittent Theta-Burst Stimulation (iTBS) treatment. Participants in the pilot group had a maximum of 2 weeks and participants in the EFS group had a maximum of three weeks to complete the 10 days of treatment.

  Up to 10 days of treatment

• Change in Brain Global Efficiency After Day One of Intermittent Theta-Burst Stimulation Treatment (Acute Effect)

  Participants received resting brain fMRI scan followed by three iTBS sessions then a second brain fMRI scan. Analysis was done to determine if iTBS alters brain networks and calculated as the difference between global efficiency (GE) before and after the first day of iTBS (pre-post). Global efficiency is a graph-theory measure that indicates how well information can be transferred across the entire brain network. A high global efficiency indicates that information can be rapidly transmitted across different brain regions due to short average path lengths between them, suggesting a well-connected and integrated brain network. It is calculated by defining N nodes and calculating the shortest pathway between each pair of nodes. The final value is 1/N(N-1) \* sum 1/shortest pathway between each pair of the N nodes. It ranges between 0 and 1 with higher values indicating greater efficiency.

  pre/post treatment day 1.

• Change in Brain Global Efficiency After Intermittent Theta-Burst Stimulation Treatment (iTBS) Course (Chronic Effect)

  Participants received baseline resting brain fMRI scan on day one and had a repeat brain fMRI two weeks after iTBS treatment course. Analysis was done to determine change in brain network with chronic treatment in cocaine dependent participants and calculated as the difference between global efficiency (GE) from baseline to post treatment (2 weeks after end of treatment). Global efficiency is a graph-theory measure that indicates how well information can be transferred across the entire brain network. A high global efficiency indicates that information can be rapidly transmitted across different brain regions due to short average path lengths between them, suggesting a well-connected and integrated brain network. It is calculated by defining N nodes and calculating the shortest pathway between each pair of nodes. The final value is 1/N(N-1) \* sum 1/shortest pathway between each pair of the N nodes. It ranges between 0 and 1 with higher values indicating greater efficiency.

  Baseline (pre-treatment) minus two weeks post treatment

• Brain Global Efficiency Before Intermittent Theta-Burst Stimulation Treatment (iTBS)

  The brain global efficiency for cocaine dependent participants and healthy control participants at baseline (pre-treatment), prior to intermittent Theta-Burst Stimulation Treatment (iTBS). Global efficiency is a graph-theory measure that indicates how well information can be transferred across the entire brain network. A high global efficiency indicates that information can be rapidly transmitted across different brain regions due to short average path lengths between them, suggesting a well-connected and integrated brain network. It is calculated by defining N nodes and calculating the shortest pathway between each pair of nodes. The final value is 1/N(N-1) \* sum 1/shortest pathway between each pair of the N nodes. It ranges between 0 and 1 with higher values indicating greater efficiency.

  Baseline (pre-treatment)

Study Arms (4)

Pilot Group

EXPERIMENTAL

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.

Device: Transcranial magnetic stimulation (TMS)

Expanded Feasibility Study (EFS): Cocaine - Active Group

EXPERIMENTAL

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.

Device: Transcranial magnetic stimulation (TMS)

Expanded Feasibility Study (EFS): Cocaine - Sham Group

SHAM COMPARATOR

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.

Device: Transcranial magnetic stimulation (TMS)

Expanded Feasibility Study (EFS): Healthy Control

OTHER

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.

Device: Transcranial magnetic stimulation (TMS)

Interventions

Transcranial magnetic stimulation (TMS) 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; Expanded Feasibility Study (EFS): Cocaine - Sham Group; Expanded Feasibility Study (EFS): Healthy Control; Pilot Group

Eligibility Criteria

• Age: 22 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Be able to give valid informed consent.
• Be 18 - 60 years of age.
• Right-handed.
• Be in good health.
• Absence of a specific learning disability, attention deficit hyperactivity disorder (ADHD) or cognitive impairment
• 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.

You may not qualify if:

• 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.
• 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.
• First-degree family history of any neurological disorder with a potentially hereditary basis, including migraines, epilepsy, or multiple sclerosis.
• 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.
• Noise-induced hearing loss or tinnitus.
• 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.
• Lifetime history of schizophrenia, bipolar disorder, mania, or hypomania.
• 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.
• 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).
• 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.
• Be able to give valid informed consent.
• Agree to also participate in study 10-DA-N457, where characterization information is gathered and shared with this protocol.
• Be 22 - 60 years of age.
• Right-handed.
• Be in good health.

Sponsors & Collaborators

• National Institute on Drug Abuse (NIDA): lead

Study Sites (1)

National Institute on Drug Abuse

Baltimore, Maryland, 21224, United States

Location

Related Publications (3)

• 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.

  PMID: 29429954 BACKGROUND

• 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.

  PMID: 39045554 BACKGROUND

• 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.

  PMID: 31736689 RESULT

MeSH Terms

Conditions

Cocaine-Related Disorders

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Results Point of Contact

• Title: Yihong Yang, PhD
• Organization: National Institute on Drug Abuse (NIDA)

yihong.yang@nih.gov

443-740-2648

Study Officials

• Yihong Yang, Ph.D.

  National Institute on Drug Abuse (NIDA)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Pilot study: open label; Expanded feasibility study: double blind, sham controlled
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: Pilot study: single arm; Expanded feasibility study: parallel arm

Study Record Dates

• First Submitted: October 6, 2016
• First Posted: October 7, 2016
• Study Start: February 13, 2017
• Primary Completion: October 30, 2023
• Study Completion: October 30, 2023
• Last Updated: February 25, 2025
• Results First Posted: February 25, 2025

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)