NCT03470480

Brief Summary

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
50

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Feb 2018

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 7, 2018

Completed
Same day until next milestone

Study Start

First participant enrolled

February 7, 2018

Completed
1 month until next milestone

First Posted

Study publicly available on registry

March 20, 2018

Completed
7.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2025

Completed
Last Updated

May 17, 2024

Status Verified

May 1, 2024

Enrollment Period

7.6 years

First QC Date

February 7, 2018

Last Update Submit

May 16, 2024

Conditions

Outcome Measures

Primary Outcomes (3)

  • 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 Outcomes (2)

  • Effect of craving for methamphetamine on relapse status after rTMS directed at left DLPFC.

    5 months

  • Effect of cue type (methamphetamine versus neutral) on methamphetamine craving after rTMS treatment.

    6 weeks

Study Arms (4)

Treatment rTMS + meth pictures

EXPERIMENTAL

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 stimulationBehavioral: Methamphetamine visual cues

Treatment rTMS + neutral pictures

ACTIVE COMPARATOR

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 stimulationBehavioral: Neutral visual cues

Sham rTMS + meth pictures

SHAM COMPARATOR

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).

Device: Sham Repetitive transcranial magnetic stimulationBehavioral: Methamphetamine visual cues

Sham rTMS + neutral pictures

SHAM COMPARATOR

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).

Device: Sham Repetitive transcranial magnetic stimulationBehavioral: Neutral visual cues

Interventions

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.

Also known as: rTMS, TMS, Magstim Rapid 2
Treatment rTMS + meth picturesTreatment rTMS + neutral pictures

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 rTMS + meth picturesSham rTMS + neutral pictures

Just before each rTMS session, participants will be shown methamphetamine-related pictures

Sham rTMS + meth picturesTreatment rTMS + meth pictures

Just before each rTMS session, participants will be shown neutral pictures

Sham rTMS + neutral picturesTreatment rTMS + neutral pictures

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Veterans Affairs Portland Health Care System

Portland, Oregon, 97239, United States

RECRUITING

MeSH Terms

Conditions

Substance-Related Disorders

Condition Hierarchy (Ancestors)

Chemically-Induced DisordersMental Disorders

Central Study Contacts

Brandon J Cornejo, MD, PhD

CONTACT

Holly McCready

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: This preliminary study aims to consent and enroll 20 individuals with Methamphetamine Use Disorder. Participants will be randomized into two rTMS conditions (real versus sham) and two picture cues conditions (METH versus neutral). Randomization provides the following four groups: real METH (RM), real neutral (RN), sham METH (SM) and sham neutral (SN). The randomizations can be performed with a web-based randomization generator (www.randomization.com) (47). Subjects and rTMS administrators will be blinded to the treatment.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor, Psychiatry

Study Record Dates

First Submitted

February 7, 2018

First Posted

March 20, 2018

Study Start

February 7, 2018

Primary Completion

September 1, 2025

Study Completion

September 1, 2025

Last Updated

May 17, 2024

Record last verified: 2024-05

Data Sharing

IPD Sharing
Will not share

Locations