Repetitive dTMS Intervention for Methamphetamine Addiction

Study Overview
=================
Brief Summary
-----------------
A growing body of evidence suggests a wide range of brain areas including medial prefrontal cortex (mPFC), dorsolateral prefrontal cortex (DLPFC) and other subcortical regions, such as anterior cingulate cortex (ACC) are critical for regulating cognitive control over decisions and involving in drug related cue processing. Previous studies have demonstrated that transcranial magnetic stimulation (rTMS) over dorsolateral prefrontal cortex reduces craving for meth dependences. Specifically, the H7 coil induces a magnetic field can target mPFC and ACC. In this study, the investigators investigated whether repeated dTMS intervention of medial prefrontal and cingulate cortices in methamphetamine addiction could reduce the subjective craving and improve the cognitive abilities.

Detailed Description
-----------------
The study will be conducted at the drug rehabilitation center in China. The whole procedure includes enrollment, pre-intervention evaluation, intervention (for 3 weeks, 5 times a week, 15 times in total), post-intervention evaluation and one month follow up evaluation. In enrollment session, participants are recruited according to inclusion criteria. In the pre-intervention evaluation, firstly, participants need complete a questionnaire to assess their demographic information, drug addiction history and drug abstinence. And then are assigned to either 10Hz group or sham group according to the counterbalance of their basic demographic and drug use information. Then, participants need complete craving, cognitive ability and electroencephalogram (EEG) assessment. For craving assessing, participants are shown a video of methamphetamine usage for 5 minutes, and then rated on the visual analogue scale (0 means completely undesired and 100 means extremely wanting) to report their craving for methamphetamine. For cognitive ability and EEG signal assessing, the whole process is conducted on the computer according to instructions. In the intervention session, dTMS was administered using a TMS stimulator (Magstim, U.K.) equipped with a unique H-shaped coil design. The H-coil version used in this study was the H7 (Brainsway, Jerusalem, Israel). When placed 4-5 cm anterior to the foot motor cortex and used at 100% of the leg resting motor threshold (RMT), the H7 coil stimulates the dorsal mPFC and ACC bilaterally. A participant's RMT was determined before the first treatment and at the beginning of each week by ascertaining the coil position that elicited the minimal involuntary contractions of the feet (three of six attempts). The 10Hz group received 10 Hz dTMS at 100% of RMT, with 3-second pulse and 17-second intervals, for a total of 50 trains and 1500 pulses per session. The sham group received treatment with identical technical parameters, which induced scalp sensations but without penetration of the electric field into the brain. Post-intervention evaluation and one month follow up evaluation are the same as in pre-intervention evaluation. To ensure study quality, some measures are taken as bellow: Researchers and drug rehabilitation staff will work together in whole process and the data will be converted into electronic versions once finishing each evaluation. In the intervention, patients, operators, and raters were blind to treatment condition. Each patient is assigned a magnetic card that determined the coil (real or sham) in the helmet and raters are not present while treatments are administered. After each treatment times, any side effect from participant's report are recorded to assure the safety and feasibility. Statistical analyses are performed using SPSS 21.0. The principal statistical analysis is performed using repeated-measures analysis of variance and regression analysis. All missing data will be recorded and marked.

Official Title
-----------------
Repetitive dTMS Intervention for Methamphetamine Addiction

Conditions
-----------------
Methamphetamine-dependence

Intervention / Treatment
-----------------
* Device: real coil
* Device: sham coil


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Methamphetamine dependents middle school degree or above Exclusion Criteria: Have contraindications to rTMS (head trauma, epilepsy or history of epilepsy, metal implant etc.) psychiatric illnesses intellectual impairment (IQ<90)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 10hz group<br>a high frequency stimulation | Device: real coil<br>* active 10Hz with a train of 3s on / 17s off, 50 trains, a total of 1500 pulses<br>|
| Sham Comparator: sham group<br>a sham coil which frequency is 10hz but do not induce stimulation | Device: sham coil<br>* sham 10Hz with a train of 3s on / 17s off, 50 trains, a total of 1500 pulses<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of Cue-induced craving and ERP | Subjective craving (cue induced, 0-100 based VAS, craving scale) and drug cue-ERP (P300 etc. measured) | the day before intervention, 3 weeks after intervention, 1 month after intervention, up to 3 months after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of cognition: behavioral inhibition | using cognitive tasks: stop-signal task | the day before intervention, 3 weeks after intervention, 1 month after intervention, up to 3 months after intervention | 
| Changes of cognition: working memory | using cognitive tasks: n-back task | the day before intervention, 3 weeks after intervention, 1 month after intervention, up to 3 months after intervention | 
| Changes of depression status | depression (Beck Depression inventory scale), high score means worse depression | the day before intervention, 3 weeks after intervention, 1 month after intervention, up to 3 months after intervention | 
| Changes of anxiety status | Anxiety (Beck anxiety inventory scale), higher score means worse anxiety | the day before intervention, 3 weeks after intervention, 1 month after intervention, up to 3 months after intervention | 
| Changes of sleep status | sleep status measurements (Pittsburgh Sleep Quality Index scale), higher score means worse sleep | the day before intervention, 3 weeks after intervention, 1 month after intervention, up to 3 months after intervention | 
| Changes of impulsivity | Impulsivity scale (The Barratt Impulsiveness Scale), higher score means higher impulsivity | the day before intervention, 3 weeks after intervention, 1 month after intervention, up to 3 months after intervention | 
| Changes of resting EEG network | resting EEG signal (Alpha, Beta, Theta, etc) measurement with 128 Channel EGI system | the day before intervention, 3 weeks after intervention, 1 month after intervention, up to 3 months after intervention | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
deep transcranial magnetic stimulation, methamphetamine addiction