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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
30
A magnetic current created by the device creates an electrical current in the brain to stimulate the medial prefrontal cortex and dorsal anterior cingulate cortex.
A sham coil is in the same helmet as the active coil. The sham coil mimics the sound, scalp sensations, and facial muscle activation caused by the active coil, but does not create an electrical current in the brain.
New York State Psychiatric Institute (NYSPI) / Substance Treatment and Research Service (STARS)
New York, New York, United States
RECRUITINGPercentage of participants receiving at least 15 out of 20 rTMS sessions
Feasibility will be measured as the total percentage of participants who receive the defined number of rTMS sessions
Time frame: 1 week
Number of participants experiencing an rTMS-emergent serious adverse event
Safety of rTMS will be measured by the absolute number of serious adverse events that occur in the active rTMS arm
Time frame: 1 week
Number of participants with 15% decrease in RSFC (resting state functional connectivity) between the DLPFC (dorsolateral prefrontal cortex) and anterior cingulate.
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
Time frame: 1 week
Percentage of participants who achieve 3 weeks of abstinence during the final 12 weeks of the trial
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
Time frame: 12 weeks
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