rTMS for Craving in Methamphetamine Use Disorder

The Use of Repetitive Transmagnetic Stimulation to Target Craving in Methamphetamine Use Disorder

The primary aim of this project is to use a randomized single-blind sham-controlled study to investigate if high frequency repetitive transmagnetic stimulation (HF-rTMS) can modulate cue-induced craving in adult methamphetamine (METH) users. The investigators hypothesize that HF-rTMS directed at left dorsolateral prefrontal cortex (DLPFC) will result in a reduction in craving for METH compared to sham-controlled rTMS in adults with methamphetamine use disorder (MUD) as evidenced by validated measures of METH craving. Neurobiologically, the investigators anticipate rTMS mediated stimulation of the DLPFC could result in inhibition of cue-induced craving through potential disruption of involved circuitry. The current project proposes that participants who are recently abstinent from METH will be randomized into four experimental groups to provide two rTMS conditions (real versus sham) and two picture cues conditions (METH versus neutral). The experiment will have an induction phase where each subject will receive 10 daily treatments within 2 weeks. Just before each rTMS/sham session participants will be shown visual cues (METH or neutral). Participants will then undergo a maintenance phase for an additional month with assessments to evaluate craving and relapse. Urine samples for urine drug screening (UDS) will be collected at screening day and on days 1, 5 and 10. Just before each rTMS/sham session participants will be shown visual cues (METH and neutral). VAS craving scores will be assessed before and after picture presentation and after the rTMS/sham session. Before the first and 10th treatment session, participants were evaluated by the the Stimulant Craving Questionnaire (STCQ) and the Severity of Dependence Scale (SDS) questionnaires. Participants will then undergo a maintenance phase for an additional month. During the first week of maintenance, three rTMS/sham sessions will be administered. During each of the following 3 weeks, one rTMS/sham session will be given per week. As with the induction phase, urine samples will be collected for screening and STCQ and the SDS questionnaires will be completed at each maintenance session. To evaluate the long-term effects of the rTMS treatment, the investigators plan on contacting participants 6 months after treatment termination for all subjects who completed the 10 treatment sessions. During that phone conversation, craving and relapse will again be assessed.

Study Overview

• Status: Recruiting
• Conditions: Transcranial Magnetic Stimulation; Methamphetamine-dependence; Substance Use Disorders; Stimulant Dependence; Methamphetamine Abuse; Stimulant Use
• Intervention / Treatment: Device: Real Repetitive transcranial magnetic stimulation; Behavioral: Methamphetamine visual cues; Behavioral: Neutral visual cues; Device: Sham Repetitive transcranial magnetic stimulation

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Brandon J Cornejo, MD, PhD; Phone Number: 503-721-7964; Email: brandon.cornejo@va.gov
• Study Contact Backup: Name: Holly McCready; Phone Number: 503-721-7964

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Veterans Affairs Portland Health Care System
      • Contact: Holly McCready; Phone Number: 503-721-7964
      • Contact: Brandon J Cornejo, MD, PhD; Phone Number: 503-721-7964
      • Principal Investigator: Brandon J Cornejo, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects must use at least 0.5 g per day at least 5 days per week and have a minimum 12-month history of METH abuse.
• Subjects must meet DSM V diagnosis for methamphetamine use disorder.
• Subjects must have a minimum 4-week period of detoxification and a desire to stop using methamphetamine.

Exclusion Criteria:

• Present or past history of neurological disorder
• The present history of a DSM IV Axis I or DSM V primary psychiatric disease (apart from MUD and depressive symptoms defined as a Hamilton Depression Scale Score < 7 ("normal"))
• Scores on the Hamilton Depression Scale > 8, possibly indicating clinical depression
• No current abuse of drugs other than methamphetamine (except nicotine). Urine-screening tests for psychoactive drugs will be performed to corroborate the lack of drug use.
• Individuals meeting criteria for cannabis use disorder or alcohol use disorder
• Medical illness that can affect brain function
• Past or present history of cardiovascular disease or high blood pressure
• Any history of epilepsy or a known history of seizure disorder
• A history of metal in the head or chest area (except dental fillings or braces)
• Current consumption of psychiatric medication
• Any other medical, neurological or neurosurgical condition that would preclude the administration of repetitive transmagnetic stimulation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment rTMS + meth pictures; Participants in this group will receive real repetitive transcranial magnetic stimulation treatments. Before each rTMS session they will be exposed to a series of methamphetamine-related pictures to evaluate response to methamphetamine visual cues while receiving real rTMS treatments. This group will be referred to as real METH (RM).	Device: Real Repetitive transcranial magnetic stimulation; A real magnet will be used during rTMS treatments, which will look identical to the sham magnet. The participants and treatment facilitator will be blinded to which magnet will be used. High frequency repetitive transmagnetic stimulation (rTMS) will be directed at left dorsolateral prefrontal cortex (DLPFC) during 10 daily treatments within two weeks then 6 more treatments during the following month.; Other Names: TMS; rTMS; Magstim Rapid 2; Behavioral: Methamphetamine visual cues; Just before each rTMS session, participants will be shown methamphetamine-related pictures
Active Comparator: Treatment rTMS + neutral pictures; Participants in this group will receive real repetitive transcranial magnetic stimulation treatments. Before each rTMS session they will be exposed to a series of neutral pictures to evaluate response to neutral visual cues while receiving real rTMS treatments. This group will be referred to as real neutral (RN).	Device: Real Repetitive transcranial magnetic stimulation; A real magnet will be used during rTMS treatments, which will look identical to the sham magnet. The participants and treatment facilitator will be blinded to which magnet will be used. High frequency repetitive transmagnetic stimulation (rTMS) will be directed at left dorsolateral prefrontal cortex (DLPFC) during 10 daily treatments within two weeks then 6 more treatments during the following month.; Other Names: TMS; rTMS; Magstim Rapid 2; Behavioral: Neutral visual cues; Just before each rTMS session, participants will be shown neutral pictures
Sham Comparator: Sham rTMS + meth pictures; Participants in this group will receive sham repetitive transcranial magnetic stimulation treatments. Before each rTMS session they will be exposed to a series of methamphetamine-related pictures to evaluate response to methamphetamine visual cues while receiving sham rTMS treatments. This group will be referred to as sham METH (SM).	Behavioral: Methamphetamine visual cues; Just before each rTMS session, participants will be shown methamphetamine-related pictures; Device: Sham Repetitive transcranial magnetic stimulation; A sham magnet will be used during rTMS treatments, which will look identical to the real magnet. The participants and treatment facilitator will be blinded to which magnet will be used. The sham rTMS treatments will be directed at left dorsolateral prefrontal cortex (DLPFC) during 10 daily treatments within two weeks then 6 more treatments during the following month.
Sham Comparator: Sham rTMS + neutral pictures; Participants in this group will receive sham repetitive transcranial magnetic stimulation treatments. Before each rTMS session they will be exposed to a series of neutral pictures to evaluate response to neutral visual cues while receiving sham rTMS treatments. This group will be referred to as sham neutral (SN).	Behavioral: Neutral visual cues; Just before each rTMS session, participants will be shown neutral pictures; Device: Sham Repetitive transcranial magnetic stimulation; A sham magnet will be used during rTMS treatments, which will look identical to the real magnet. The participants and treatment facilitator will be blinded to which magnet will be used. The sham rTMS treatments will be directed at left dorsolateral prefrontal cortex (DLPFC) during 10 daily treatments within two weeks then 6 more treatments during the following month.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of rTMS directed at left DLPFC on craving for methamphetamine as assessed by the Severity of Dependence Scale.	The Severity of Dependence Scale (SDS) is a 5-item questionnaire that provides a score indicating the severity of dependence on methamphetamine. Each of the five items is scored on a 4-point scale (0-3). The total score is obtained through the addition of the 5-item ratings and will range from 0 to 15. The higher the score the higher the level of dependence. Pre and post differences in craving will be assessed.	6 weeks
Effect of rTMS directed at left DLPFC on craving for methamphetamine as assessed by a Visual Analog Scale (VAS).	The visual analogue scale (VAS) is a fixed-length horizontal line on which the participant draws a line between the two anchors of "no cravings at all" and "most intense craving imaginable". The distance between the "no cravings at all" anchor and the participants line is measured and reported as a value between 0 and 100. The higher the value, the more intense the participants cravings are. Pre and post differences in craving will be assessed.	6 weeks
Effect of rTMS directed at left DLPFC on craving for methamphetamine as assessed by the Stimulant Craving Questionnaire (STCQ).	The Stimulant Craving Questionnaire-Brief (STCQ) is a 10-item self-report measure that assesses current craving for methamphetamine, using a seven-point scale, with answers ranging from 0 ("strongly disagree") to 6 ("strongly agree"). A composite score is generated for each participant by averaging the responses over all 10 questions. The scores can range from 0 to 6. The higher the composite score, the stronger the current craving. Pre and post differences in craving will be assessed.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of craving for methamphetamine on relapse status after rTMS directed at left DLPFC.	Relapse will be determined by self-report and/or positive urine drug screens.	5 months
Effect of cue type (methamphetamine versus neutral) on methamphetamine craving after rTMS treatment.	A composite craving score will be generated by adding each of the three craving measure scores (Severity of Dependence, Visual Analog Scale, and Stimulant Craving Questionnaire) for each participant who received real rTMS treatments. The composite score can range from 0 to 121, where 0 indicates no cravings for methamphetamine and 121 is the strongest possible cravings for methamphetamine. Pre and post differences in craving will be compared between participants who were exposed to methamphetamine cues before each session and those who were exposed to neutral cues.	6 weeks

Collaborators and Investigators

• Sponsor: Oregon Health and Science University

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2018
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): September 1, 2023

Study Registration Dates

• First Submitted: February 7, 2018
• First Submitted That Met QC Criteria: March 16, 2018
• First Posted (Actual): March 20, 2018

Study Record Updates

• Last Update Posted (Actual): September 22, 2021
• Last Update Submitted That Met QC Criteria: September 16, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Sympathomimetics; Adrenergic Uptake Inhibitors; Methamphetamine
• Other Study ID Numbers: GPSYC0236A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No