Repetitive dTMS Intervention for Methamphetamine Addiction

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.

Study Overview

• Status: Completed
• Conditions: Methamphetamine-dependence
• Intervention / Treatment: Device: real coil; Device: sham coil

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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Nanjing, China, 210090
    • Nanjing Dalianshan Addiction Rehab Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
side effect measurements	Side effect scale, including headache, pricking, sleeplessness etc.	every day after each intervention time for the 3 weeks intervention time period

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center
• Investigators: Principal Investigator: Tifei Yuan, PhD, Shanghai Mental Health Center

Publications and helpful links

General Publications

• Shen Y, Cao X, Tan T, Shan C, Wang Y, Pan J, He H, Yuan TF. 10-Hz Repetitive Transcranial Magnetic Stimulation of the Left Dorsolateral Prefrontal Cortex Reduces Heroin Cue Craving in Long-Term Addicts. Biol Psychiatry. 2016 Aug 1;80(3):e13-4. doi: 10.1016/j.biopsych.2016.02.006. Epub 2016 Feb 12. No abstract available.
• Dunlop K, Hanlon CA, Downar J. Noninvasive brain stimulation treatments for addiction and major depression. Ann N Y Acad Sci. 2017 Apr;1394(1):31-54. doi: 10.1111/nyas.12985. Epub 2016 Feb 5.
• Carmi L, Tendler A, Bystritsky A, Hollander E, Blumberger DM, Daskalakis J, Ward H, Lapidus K, Goodman W, Casuto L, Feifel D, Barnea-Ygael N, Roth Y, Zangen A, Zohar J. Efficacy and Safety of Deep Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder: A Prospective Multicenter Randomized Double-Blind Placebo-Controlled Trial. Am J Psychiatry. 2019 Nov 1;176(11):931-938. doi: 10.1176/appi.ajp.2019.18101180. Epub 2019 May 21.
• Liu T, Li Y, Shen Y, Liu X, Yuan TF. Gender does not matter: Add-on repetitive transcranial magnetic stimulation treatment for female methamphetamine dependents. Prog Neuropsychopharmacol Biol Psychiatry. 2019 Jun 8;92:70-75. doi: 10.1016/j.pnpbp.2018.12.018. Epub 2018 Dec 31.
• Su H, Zhong N, Gan H, Wang J, Han H, Chen T, Li X, Ruan X, Zhu Y, Jiang H, Zhao M. High frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex for methamphetamine use disorders: A randomised clinical trial. Drug Alcohol Depend. 2017 Jun 1;175:84-91. doi: 10.1016/j.drugalcdep.2017.01.037. Epub 2017 Mar 29.
• Liu Q, Shen Y, Cao X, Li Y, Chen Y, Yang W, Yuan TF. Either at left or right, both high and low frequency rTMS of dorsolateral prefrontal cortex decreases cue induced craving for methamphetamine. Am J Addict. 2017 Dec;26(8):776-779. doi: 10.1111/ajad.12638. Epub 2017 Nov 14.

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2019
• Primary Completion (Actual): May 30, 2023
• Study Completion (Actual): October 30, 2023

Study Registration Dates

• First Submitted: November 30, 2019
• First Submitted That Met QC Criteria: December 16, 2019
• First Posted (Actual): December 18, 2019

Study Record Updates

• Last Update Posted (Estimated): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 21, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: methamphetamine addiction; deep transcranial magnetic stimulation
• Additional Relevant MeSH Terms: Compulsive Behavior; Impulsive Behavior; Behavior, Addictive
• Other Study ID Numbers: TFYuan

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: share all IPD that underlie results in a publication
• IPD Sharing Time Frame: Within twelve months after the trial complete
• IPD Sharing Access Criteria: share to health care personnel, patients and the general public.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No