Augmenting Cognitive-behavioral Therapy With rTMS of the Medial Prefrontal and Anterior Cingulate Cortices for the Treatment of Cocaine Use Disorder
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Percentage of participants who achieve 3 weeks of abstinence during the final 12 weeks of the trial
研究概览
简要总结
The goal of the study is to investigate the feasibility, safety, and effect of rTMS on mPFC/dACC activity using a combination of fMRI and clinical outcome measures, when used as an augmentation to CBT. Our hypothesis is that we will meet the following milestones prior to moving forward to the UH3 phase (a clinical trial for CUD).
- Feasibility: At least 75% of participants will receive at least 15 out of 20 rTMS sessions with no participants experiencing a study-related serious adverse event
- Mechanism: Compared to baseline, after 1 week of rTMS, participants who received active rTMS will demonstrate a 15% decrease in RSFC (resting state functional connectivity) between the DLPFC (dorsolateral prefrontal cortex) and anterior cingulate
- Efficacy: During the final 12 weeks of the trial (weeks 2-13), at least 15% of participants who received active rTMS will demonstrate 3 consecutive weeks of abstinence
Participants will:
- Have two brain MRI scans;
- Undergo 1 week of daily rTMS (or sham) treatments (up to 20 sessions), and;
- Have 12 weeks of once-weekly cognitive-behavioral therapy for the treatment of cocaine use disorder.
Researchers will compare active (real) rTMS to sham (placebo) rTMS. All participants will receive cognitive-behavioral therapy.
The former principle investigator, Dr. Derek Blevins, has vacated his position (February 2025), and has transferred the principle investigator role to Dr. John Mariani, the STARS Clinic Director.
详细描述
Cocaine use disorder (CUD) is significant public health problem in the U.S. There are no FDA approved medications and many people fail to respond to behavioral therapies, meaning that effective treatment strategies are needed. Previous studies have shown that transcranial magnetic stimulation (rTMS) can reduce cocaine use, although many of these studies have been preliminary and didn't have a control group using sham (placebo) rTMS. Thus, the goal of this study is to use a controlled design to assess rTMS as a treatment. Furthermore, we will use the H-7 coil, which is currently FDA cleared for the treatment for obsessive-compulsive disorder (OCD) and major depressive disorder
The trial will use an accelerated protocol to deliver rTMS, where multiple sessions are delivered in a single day [Roth et al, 2023, Cole et al. 2022]. Previous studies delivered up to 10 sessions per day [Cole et al., 2022]. In this study, we will deliver up to 5 sessions daily, which has been done previously using the H coil [Roth et al., 2023]. Accelerated protocols can decrease the time to improvement from weeks to about 5 days [Roth et al., 2023].
This is a randomized, double-blind, sham-controlled trial to evaluate the feasibility, neural mechanism, and clinical efficacy of H-7 coil repetitive transcranial magnetic stimulation (rTMS) in 30 individuals with cocaine use disorder (CUD) when used as an augmentation to standardized cognitive-behavioral therapy (CBT). After informed consent, participants will be randomized 2:1 to active iTBS rTMS (n=20) or sham rTMS (n=10). They will undergo baseline assessments and fMRI scans, followed by 1 week of rTMS (up to 5 sessions a day), followed by 12 weeks of weekly in-person or virtual (telemedicine) CBT, for a total of 13 weeks. fMRI scans will be repeated after the rTMS week and before initiating CBT. One brief phone assessment will be completed at week 17.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-blind
入排标准
- 年龄范围
- 22 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to give informed consent and comply with study procedures;
- •Meets DSM-5 criteria for current moderate/severe CUD and are treatment-seeking;
- •Used cocaine at least 9 days in the past 28 days, with at least weekly cocaine use;
- •Agree to no more than moderate alcohol consumption (<15 drinks/week for men and <8 drinks/week for women) and to avoid using amphetamine/methamphetamine and non-prescribed benzodiazepines or barbiturates; and
- •Women of childbearing potential must agree to use a method of contraception with proven efficacy and agree to not become pregnant during the study.
排除标准
- •Meets DSM-5 criteria for current moderate/severe major depressive episode, OCD, bipolar disorder, schizophrenia or any psychotic disorder other than transient psychosis due to substance use;
- •Hamilton Depression Rating Scale score > 17;
- •Young Mania Rating Scale score >10;
- •Meets DSM-5 criteria for current moderate/severe other substance use disorder (aside from tobacco use disorder; physiologic dependence on any other substance other than nicotine, including alcohol, is exclusionary);
- •Heavy weekly alcohol drinking as defined by an average of >14 drinks/week for men or >7 drinks/week for women on average during the past 28 days;
- •Prior alcohol, benzodiazepine, or barbiturate withdrawal that resulted in hospitalization, medical detoxification, or resulted in seizures or delirium tremens;
- •More than twice weekly use of non-prescribed medications/drugs that may change the seizure threshold, including benzodiazepines, barbiturates, GHB/GBL, amphetamines/methamphetamine;
- •Any other current DSM-5 psychiatric disorder(s) that in the investigator's judgment are unstable, would be disrupted by study procedures, or are likely to require pharmacotherapy or psychotherapy during the study period;
- •Significant current risk of suicide, indicated by either: (1) "yes" response on #3, #4, or #5 on the C-SSRS and a psychiatric risk assessment indicating a moderate or high risk of suicide or (2) suicidal behavior in the past year that, in the opinion of the clinician, increases risk of future suicidal behavior over the study period (note: non-suicidal self-injurious behavior is not exclusionary).
- •Females with a positive urine pregnancy test and/or breast feeding
- •Clinically significant abnormal cardiac functioning per electrocardiogram (ECG) (required for any participant age 60 years and older);
- •Seizure history including: seizure disorder/epilepsy, alcohol/drug withdrawal seizure, or seizure deemed by the study physician to be related to cocaine intoxication/withdrawal (note: febrile seizures are not exclusionary)
- •Other conditions associated with seizure: epilepsy and the following acute or subacute neurologic disorders: stroke (ischemic or hemorrhagic), multiple sclerosis, traumatic brain injury (moderate or severe), neurosurgery, meningoencephalitis, increased intracerebral pressure, or intracerebral abscess, neurodegenerative disorders, and parenchymal or leptomeningeal brain tumors (per the TMS core guidelines which is attached).
- •Participants with a history of metabolic abnormalities (hyponatremia, hypocalcemia, hypomagnesemia, hypo or hyperglycemia, renal failure/uremia, liver failure), recent infection with fever, and serious alcohol withdrawal will be assessed by the MD/NP to ensure these conditions have resolved and are not currently present (per the TMS core guidelines which is attached).
- •In this protocol, we will also exclude glaucoma, severe migraine (particularly complicated migraines with significant aura and hemiparesis, and severe vertebrobasilar migraines, that may lead to brainstem infarctions).
- •Medications that lower seizure threshold and in the opinion of the investigator impose significant seizure risk for the individual (including tricyclic antidepressants, monoamine oxidase inhibitors, bupropion, clozapine, and anticholinergics). The use of lithium, antipsychotics (other than clozapine), antibiotics, antihistamines, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors will be carefully assessed by the physician
- •Cognitive disorder (MMSE <25);
- •Disqualifying response on the TMS Adult Safety Screen (TASS);
- •Implanted devices or stimulators (cardiac pacemakers, vagus nerve stimulators, spinal cord stimulators, cochlear implant, implanted brain stimulators)
- •Currently taking ototoxic medications (aminoglycosides, cisplatin);
- •Metal implants or paramagnetic objects in the body that prohibits MR scanning;
- •Claustrophobia that prohibits MR scanning; or
- •Legally mandated (e.g., to avoid incarceration or other penalties) to participate in SUD treatment program.
- •Moderate to severe heart disease
研究组 & 干预措施
Sham (placebo) rTMS
Sham rTMS uses the same device and mimics the auditory and scalp sensations without stimulating the brain.
干预措施: Sham H7-coil repetitive transcranial magnetic stimulation (rTMS) (Device)
Active iTBS rTMS
Daily repetitive transcranial magnetic brain stimulation for 1 week (20 sessions).
干预措施: Active H7-coil repetitive transcranial magnetic stimulation (rTMS) (Device)
结局指标
主要结局
Percentage of participants who achieve 3 weeks of abstinence during the final 12 weeks of the trial
时间窗: 12 weeks
Efficacy regarding cocaine use outcomes will be evaluated by comparing the active and sham rTMS groups during the final 12 weeks of the trial while the participants are receiving cognitive behavioral therapy. 3 consecutive weeks of abstinence, as defined by no self-reported cocaine use using the timeline follow-back method and confirmed by qualitative urine benzoylecgonine screening
Percentage of participants receiving at least 15 out of 20 rTMS sessions
时间窗: 1 week
Feasibility will be measured as the total percentage of participants who receive the defined number of rTMS sessions
Number of participants experiencing an rTMS-emergent serious adverse event
时间窗: 1 week
Safety of rTMS will be measured by the absolute number of serious adverse events that occur in the active rTMS arm
Number of participants with 15% decrease in RSFC (resting state functional connectivity) between the DLPFC (dorsolateral prefrontal cortex) and anterior cingulate.
时间窗: 1 week
Neural mechanism will be evaluated by comparing the active and sham rTMS groups during the fMRI task by comparing baseline fMRI and post-rTMS fMRI measures
次要结局
未报告次要终点
研究者
John Mariani MD
Professor of Clinical Psychiatry
New York State Psychiatric Institute