Neuroplasticity Following Theta-Burst Stimulation in Cocaine Use Disorder
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Number of Cocaine Dependent Participants Who Tolerated Intermittent Theta-Burst Stimulation Sessions
研究概览
简要总结
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).
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Pilot study: open label; Expanded feasibility study: double blind, sham controlled
入排标准
- 年龄范围
- 22 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •INCLUSION CRITERIA - PILOT PHASE: P1:
- •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.
排除标准
- •PILOT PHASE: P1:
- •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-N
- •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.
- •INCLUSION CRITERIA - EXPANDED FEASIBILITY PHASE (EFS):
- •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.
- •Absence of a specific learning disability, ADHD or cognitive impairment
- •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.
- •Treatment seeking CD participants
- •MRI compatible
- •EXCLUSION -EFS
- •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 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-N
- •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.
- •First-degree family history of any form of epilepsy with a potentially hereditary basis .
- •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.
- •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).
- •Participation in any NIBS session less than two weeks prior to admission. No NIBS exposure for treatment purposes in the last 6 months.
- •Non-English speaking.
研究组 & 干预措施
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.
干预措施: Transcranial magnetic stimulation (TMS) (Device)
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.
干预措施: Transcranial magnetic stimulation (TMS) (Device)
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.
干预措施: Transcranial magnetic stimulation (TMS) (Device)
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.
干预措施: Transcranial magnetic stimulation (TMS) (Device)
结局指标
主要结局
Number of Cocaine Dependent Participants Who Tolerated Intermittent Theta-Burst Stimulation Sessions
时间窗: Up to 10 days of treatment
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.
Change in Brain Global Efficiency After Day One of Intermittent Theta-Burst Stimulation Treatment (Acute Effect)
时间窗: pre/post treatment day 1.
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.
Change in Brain Global Efficiency After Intermittent Theta-Burst Stimulation Treatment (iTBS) Course (Chronic Effect)
时间窗: Baseline (pre-treatment) minus two weeks post treatment
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.
Brain Global Efficiency Before Intermittent Theta-Burst Stimulation Treatment (iTBS)
时间窗: Baseline (pre-treatment)
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.
次要结局
未报告次要终点