Transcranial Magnetic Stimulation for Methadone Maintenance Therapy Combined With Methamphetamine Abuse

Study Overview
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Brief Summary
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Repetitive transcranial magnetic stimulation (rTMS) has been used to treat opioid and methamphetamine addiction in previous studies, while no evidence was proved for patients methadone maintenance therapy with methamphetamine abuse. The aim of this study is to evaluating the effectiveness and safety of rTMS treatment for methamphetamine abuse in patients with methadone maintenance therapy.

Detailed Description
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First, a multicenter, double-blind, randomized control study is going to be carried out. 100 recruited patients will be randomized assigned to the intervention group and the control group, receiving either 4-week of repetitive transcranial magnetic stimulation (rTMS) treatment or 4-week of sham rTMS treatment. Both groups will receive 16-week urine drug test (1 time per week, 4 weeks before rTMS, 4 weeks during rTMS and 8 weeks after rTMS). Negative rate of urine test for methamphetamine is set as primary outcome. Cognitive function and craving are also evaluated before and after the intervention. Functional magnetic resonance imaging (fMRI) is applied to investigate the potential neurobiological mechanism of rTMS treatment. This study will be very helpful to develop an evidence-based rTMS treatment protocols for methadone maintenance therapy with methamphetamine abuse and decrease risk of relapse for both the patients and their families.

Official Title
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Transcranial Magnetic Stimulation for Treating Patients Under Methadone Maintenance Therapy Combined With Methamphetamine Abuse

Conditions
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Methamphetamine Abuse

Intervention / Treatment
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* Device: repetitive transcranial magnetic stimulation (rTMS)
* Device: sham repetitive transcranial magnetic stimulation (rTMS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Currently in methadone maintenance therapy In accordance with the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) for methamphetamine (MA) use disorders Junior high school degree or above Normal vision and hearing Exclusion Criteria: Have a disease that affect cognitive function such as history of head injury, cerebrovascular disease, epilepsy, etc Have cognitive-promoting drugs in the last 6 months Other substance abuse or dependence in recent five years (except nicotine) Mental impairment, Intelligence Quotient (IQ) < 70 Mental disorders according to DSM-5 criteria Physical diseases

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rTMS treatment group<br>For rTMS treatment, we will stimulate the dorsal lateral prefrontal cortex of each patients using the iTBS pattern everyday. Treatment will lasted for 4 weeks. | Device: repetitive transcranial magnetic stimulation (rTMS)<br>* The iTBS group received 900 pulses per day: 3-pulse 50-Hz bursts given every 200 ms (at 5 Hz), 2 s on and 8 s off for 5 min, at 100% resting motor threshold (rMT), over the left DLPFC (F3, EEG system) (4 weeks, 20 daily sessions). A figure-8-shaped Cool-B70 stimulation coil from MagPro X100 device (MagVenture, Farum, Denmark) was used for accurately targeted stimulation. Motor threshold was determined over the left motor cortex, by finding the lowest intensity that produced a motor response in the right abductor pollicis brevis muscles (APB), which produced five motor-evoked potentials responses of at least 50 mV in 10 trials.<br>|
| Sham Comparator: sham rTMS treatment group<br>For sham rTMS treatment, we will stimulate the dorsal lateral prefrontal cortex of each patients using the sham iTBS pattern and sham coil everyday. Treatment will lasted for 4 weeks. | Device: sham repetitive transcranial magnetic stimulation (rTMS)<br>* The iTBS group received 900 pulses per day: 3-pulse 50-Hz bursts given every 200 ms (at 5 Hz), 2 s on and 8 s off for 5 min, at 100% resting motor threshold (rMT), over the left DLPFC (F3, EEG system) (4 weeks, 20 daily sessions). A figure-8-shaped sham Cool-B70 stimulation coil from MagPro X100 device (MagVenture, Farum, Denmark) was used for accurately targeted stimulation. Motor threshold was determined over the left motor cortex, by finding the lowest intensity that produced a motor response in the right abductor pollicis brevis muscles (APB), which produced five motor-evoked potentials responses of at least 50 mV in 10 trials.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Negative rate urine test | Patients will be asked to participate urine test for 16 weeks once a week. Loss of visit or rejection for urine test will be treated as urine test positive. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Craving assessed by Visual Analog Scale | Evaluate all participants' craving for for methamphetamine assessed by Visual Analog Scales (VAS). Score of VAS range from 0 to 10, and higher values represent high level of craving. | 12 weeks | 
| Cognitive function assessed by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) | Evaluate all participants' cognitive function by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Chinese version | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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repetitive transcranial magnetic stimulation (rTMS), methamphetamine abuse, methadone maintenance therapy, urine test, relapse