Cocaine Abuse, Cocaine Dependence, Cocaine Use Disorder, Methamphetamine Abuse, Methamphetamine Dependence, Methamphetamine Use Disorder, Stimulant Abuse, Stimulant Use, Stimulant Use Disorder
Conditions
Keywords
Stimulant, Cocaine, Methamphetamine, Repetitive Transcranial Magnetic Stimulation, rTMS
Brief summary
The purpose of the study is to determine feasibility of repetitive transcranial magnetic stimulation (rTMS) for individuals with moderate to severe cocaine or methamphetamine use disorder (CUD/MUD). Potential participants will be age 18-65, and interested in cutting down or stopping use. Participants will be randomized to one of two groups; groups will receive rTMS or sham rTMS (placebo) over the course of an 8-week treatment period, and complete follow-up assessments at the end of treatment, 12, and 16 weeks post-randomization.
Detailed description
The study will be a randomized, double-blind, sham-controlled trial comparing rTMS vs. placebo delivered over an 8-week treatment period. After assessment and inclusion into the study, participants will be randomized to receive up to 30 sessions of either rTMS or placebo treatments. The target minimum number of rTMS/placebo treatments is 20 treatments over 8 weeks. The secondary objective is to gather preliminary data on the efficacy of rTMS for individuals with moderate to severe CUD or MUD. Follow-up visits occur at end of treatment and at 12- and 16-weeks following randomization. Other study procedures: Actigraphy: To assess daily sleep quality during weeks 1-8, the ActiGraph wristband device will record, sleep latency, sleep duration, and intervals of waking during the sleep period. Electroencephalography (EEG): EEG will be obtained after randomization and again at week 4, to explore the potential for EEG to be used as a biomarker of treatment response. Cognitive-Behavioral Educational Intervention: Participants in both conditions (rTMS and placebo) will be encouraged to participate in a mobile app-based educational intervention based on principles of Cognitive Behavioral Therapy (CBT) for Substance Use Disorder (SUD). Daily Assessments: Brief, electronic remote surveys will be administered to participants daily until week 16 follow-up time point and will assess use of primary substance of abuse, craving, ability to resist use, overall mood, and self-rated sleep quality. Urine Drug Screens (UDS): UDS will be collected at screening, randomization, every treatment session, and at follow-up visits. Urine pregnancy tests: Pregnancy testing for all female participants will be performed at screening, randomization, and monthly during the treatment period. Physical exam: A physical exam will be performed at screening. Questionnaires: A battery of study assessments will be completed to further inform findings regarding feasibility and effects of rTMS on individuals with stimulant use disorders.
Interventions
DEVICErTMS
Each rTMS session will consist of 75 rTMS trains of 10 Hz for 4 seconds (40 pulses per train) with inter-train interval (ITI) of 11 seconds (a total of 3000 stimuli per session) over the left dorsolateral prefrontal cortex (DLPFC).
DEVICESham (Placebo)
Each sham rTMS session will consist of 75 rTMS trains of 10 Hz for 4 seconds (40 pulses per train) with inter-train interval (ITI) of 11 seconds (a total of 3000 stimuli per session) over the left dorsolateral prefrontal cortex (DLPFC). In the placebo condition the magnetic field will be delivered in the opposite direction (away from the brain).
Sponsors
National Institute on Drug Abuse (NIDA)
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
This is a double-blind, sham-controlled study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 18-65, inclusive * Have a diagnosis of moderate or severe Cocaine or Methamphetamine Use Disorder (CUD/MUD) over the past 12 months (as determined by DSM-5 diagnostic criteria). * Have used cocaine or methamphetamine on at least 10 of the last 30 days (based on Timeline Follow-Back). * Be interested in decreasing cocaine and/or methamphetamine use. * If female, willing to use appropriate birth control method during the treatment phase of the study. * Be able to understand the study procedures and provide written informed consent to participate in the study. * If prescribed benzodiazepines or anticonvulsants, must be on a stable dose for at least 4 weeks prior to consent.
Exclusion criteria
* A Diagnostic and Statistical Manual (DSM-5) diagnosis of moderate or severe SUD of any substance other than cocaine or methamphetamine based on DSM-5. * History of a serious medical disorder that, in the opinion of the Medical Clinician, would make it unsafe to participate in the study or may prevent collection of study data. * Is currently engaged in formal SUD treatment. * Documented history of unprovoked seizure (lifetime) or any seizure in the past 6 months. * Documented history of brain lesion(s) and/or tumor(s). * Metal implants or non-removable metal objects above the waist. * Currently pregnant. * Lifetime history of prior clinical treatment with TMS. * Current or lifetime bipolar disorder. * Current psychotic disorder or psychotic depression. * Serious risk of homicide or suicide. * Are a prisoner or in police custody at the time of eligibility screening. * Previously randomized as a participant in the study. * Planned admission to a residential treatment facility or other formal SUD treatment program. * Unwilling or unable to follow study procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Receive at Least 20 Sessions of rTMS/Sham Over the Treatment Period. | From first treatment session (Week 1, first study visit) to end of treatment at 8 weeks | Treatment session attendance and completion will be tracked over the course of the study, and this record will constitute the primary feasibility outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Negative UDS From Weekly UDS | From first treatment week (Week 1) to end of treatment at 8 weeks | A negative UDS for participants with cocaine as primary substance would be a UDS absent of cocaine; a negative UDS for participants with methamphetamine as primary substance would be a UDS absent of methamphetamine. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| rTMS Participants will receive up to 30 rTMS sessions within the 8-week treatment period.
rTMS: Each rTMS session will consist of 75 rTMS trains of 10 Hz for 4 seconds (40 pulses per train) with inter-train interval (ITI) of 11 seconds (a total of 3000 stimuli per session) over the left dorsolateral prefrontal cortex (DLPFC). | 66 |
| Sham (Placebo) Participants will receive up to 30 sham rTMS sessions within the 8-week treatment period.
Sham (Placebo): Each sham rTMS session will consist of 75 rTMS trains of 10 Hz for 4 seconds (40 pulses per train) with inter-train interval (ITI) of 11 seconds (a total of 3000 stimuli per session) over the left dorsolateral prefrontal cortex (DLPFC). In the placebo condition the magnetic field will be delivered in the opposite direction (away from the brain). | 63 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Incarcerated | 1 | 1 |
| Overall Study | Lost to Follow-up | 9 | 18 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Unable to attend visits | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | rTMS | Sham (Placebo) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 65 Participants | 62 Participants | 127 Participants |
| Age, Continuous | 46.8 years STANDARD_DEVIATION 9.38 | 46.8 years STANDARD_DEVIATION 10.2 | 46.8 years STANDARD_DEVIATION 9.77 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 8 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 55 Participants | 55 Participants | 110 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Major Depressive Episode Absent | 61 Participants | 59 Participants | 120 Participants |
| Major Depressive Episode Present | 5 Participants | 4 Participants | 9 Participants |
| Primary substance of use Cocaine | 27 Participants | 26 Participants | 53 Participants |
| Primary substance of use Methamphetamine | 39 Participants | 37 Participants | 76 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 26 Participants | 28 Participants | 54 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) White | 32 Participants | 30 Participants | 62 Participants |
| Region of Enrollment United States | 66 participants | 63 participants | 129 participants |
| Sex: Female, Male Female | 20 Participants | 13 Participants | 33 Participants |
| Sex: Female, Male Male | 46 Participants | 50 Participants | 96 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 66 | 0 / 63 |
| other Total, other adverse events | 45 / 66 | 29 / 63 |
| serious Total, serious adverse events | 5 / 66 | 2 / 63 |
Outcome results
Primary
Percentage of Participants Who Receive at Least 20 Sessions of rTMS/Sham Over the Treatment Period.
Treatment session attendance and completion will be tracked over the course of the study, and this record will constitute the primary feasibility outcome.
Time frame: From first treatment session (Week 1, first study visit) to end of treatment at 8 weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rTMS | Percentage of Participants Who Receive at Least 20 Sessions of rTMS/Sham Over the Treatment Period. | Attended 20 or more rTMS/sham sessions | 29 Participants |
| rTMS | Percentage of Participants Who Receive at Least 20 Sessions of rTMS/Sham Over the Treatment Period. | Attended fewer than 20 rTMS/sham sessions | 37 Participants |
| Sham (Placebo) | Percentage of Participants Who Receive at Least 20 Sessions of rTMS/Sham Over the Treatment Period. | Attended 20 or more rTMS/sham sessions | 40 Participants |
| Sham (Placebo) | Percentage of Participants Who Receive at Least 20 Sessions of rTMS/Sham Over the Treatment Period. | Attended fewer than 20 rTMS/sham sessions | 23 Participants |
Secondary
Negative UDS From Weekly UDS
A negative UDS for participants with cocaine as primary substance would be a UDS absent of cocaine; a negative UDS for participants with methamphetamine as primary substance would be a UDS absent of methamphetamine.
Time frame: From first treatment week (Week 1) to end of treatment at 8 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| rTMS | Negative UDS From Weekly UDS | Negative UDS | 38 Urine drug screens |
| rTMS | Negative UDS From Weekly UDS | Positive UDS | 369 Urine drug screens |
| Sham (Placebo) | Negative UDS From Weekly UDS | Negative UDS | 30 Urine drug screens |
| Sham (Placebo) | Negative UDS From Weekly UDS | Positive UDS | 384 Urine drug screens |