Testing an Accelerated TMS Protocol for Methamphetamine Use Disorder

The investigators will evaluate the effects of an accelerated Transcranial Magnetic Stimulation (TMS) protocol of the left dorsolateral prefrontal cortex (DLPFC) for moderate to severe methamphetamine use disorder. This is a randomized parallel group design to assess feasibility and safety, evaluate efficacy (use, craving) and identify magnetic resonance imaging (resting state and cue craving) associated with group/outcomes.

Study Overview

• Status: Not yet recruiting
• Conditions: Methamphetamine Use Disorder
• Intervention / Treatment: Device: Sham TMS; Device: Active TMS

Detailed Description

In a randomized double-blind parallel-group sham-controlled design (n=20) administer a 5-day accelerated iTBS protocol (40 treatments) to the left dorsolateral prefrontal cortex during a short inpatient stay. Magnetic resonance imaging will be completed pre-post TMS and participants will be followed for 12 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Joseph T Sakai, MD; Phone Number: 303-724-7402; Email: joseph.sakai@cuanschtz.edu
• Study Contact Backup: Name: Kristen M Raymond, BA; Phone Number: 303-724-3196; Email: kristen.raymond@cuanschutz.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Campus
      • Contact: Kristen M Raymond, BA; Phone Number: 303-724-3196; Email: kristen.raymond@cuanschutz.edu
      • Contact: Joseph T Sakai, MD; Phone Number: 303-724-7402; Email: joseph.sakai@cuanschutz.edu
      • Principal Investigator: Joseph T Sakai, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 21-65 years inclusive;
2. Meets DSM-5 criteria for past-year moderate or severe methamphetamine use disorder;
3. By Timeline Follow Back endorses at least 10 days of methamphetamine use out of the last month;
4. Provides a urine drug screen positive for methamphetamine;
5. Able to provide informed consent;
6. No change in current psychiatric medication regimen, or medication free, for at least 4 weeks prior to study entry;
7. Adequate English proficiency for study consent, and completion of the study instruments.

Exclusion Criteria:

1. Lifetime non-substance-induced psychotic disorders, schizophrenia, schizoaffective disorder or bipolar disorder defined by DSM-5;
2. Current diagnosis of DSM-5 drug use disorder other than stimulant, cannabis or nicotine use disorder;
3. Non-substance-induced manic episode within the past 3 years or major depressive episode in the past year;
4. Current clinically significant neurological disorder or medical illness, including history of seizures, cardiovascular disease/cardiac event, which in the opinion of the study physician would make study participation unsafe;
5. Presence of a clinically significant abnormality on baseline MRI;
6. Inability to have an MRI;
7. Currently breastfeeding, is currently pregnant or lack of use of effective contraception in women of childbearing age, as assessed by urine pregnancy test and self-report (participants will consent to continue effective contraceptives during the study);
8. Active criminal justice involvement (i.e., any unresolved legal problems that could jeopardize continuation or completion of the study);
9. History of head injury with loss of consciousness for more than 15 minutes;
10. Diagnosis of dementia;
11. Prescribed benzodiazepines or anticonvulsants;
12. Currently enrolled in formal substance use disorder treatment;
13. Metal implants or non-removable metal objects above the waist;
14. Lifetime history of prior clinical treatment with TMS;
15. Serious risk of suicide or homicide;
16. Unable/unwilling to follow the study procedures;
17. History of intractable migraine;
18. Assessed to be at risk for alcohol or opioid withdrawal.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Sham TMS; Participants have baseline assessments/evaluation, are admitted to the inpatient research unit, randomized via permuted block design to 5 days of sham TMS, and then have weekly study visits for the next 12 weeks.	Device: Sham TMS; The TMS Cool-B65 A/P coil on its placebo side delivers electrical stimulation to the scalp (e.g., mimicking sensations associated with real stimulation) but does not provide magnetic stimulation to the targeted cortical structure.
Experimental: Active TMS; Participants have baseline assessments/evaluation, are admitted to the inpatient research unit, randomized via permuted block design to 5 days of active TMS, and then have weekly study visits for the next 12 weeks.	Device: Active TMS; The TMS Cool-B65 A/P coil delivers magnetic stimulation to targeted cortical structure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability	Proportion completing at least 20 TMS session - sham vs. active	5 days
Study emergent adverse events	Incidence of study emergent adverse events - sham vs. active	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weeks of continuous abstinence	Number of weeks of continuous methamphetamine abstinence - sham vs. active as measured weekly by urine drug screen.	12 weeks
Days of methamphetamine use	Number of days of methamphetamine use - sham vs. active as measured weekly by timeline followback interview.	12 weeks
Methamphetamine craving	Craving as measured on the Stimulant Craving Questionnaire-Brief - sham vs. active. Each item is scored 0-6 (from Strongly Disagree=0 to Strongly Agree=6) with items #4 and #7 reverse scored. The investigators will average all 10 items as the total score, with higher scores indicating greater levels of craving.	12 weeks
Methamphetamine craving on visual analog scale	Craving as measured on visual analog scale - sham vs. active. Scored 0 to 100 with 0=no craving and 100=the most craving.	12 weeks
MRI cue craving	Cue craving data will be collected pre- and post-TMS stimulation in week 1	Pre- and Post- TMS stimulation in week 1
MRI resting state	Resting state data will be collected pre- and post-TMS stimulation in week 1	Pre- and Post- TMS stimulation in week 1

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Institute on Drug Abuse (NIDA)

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): May 31, 2028

Study Registration Dates

• First Submitted: March 13, 2024
• First Submitted That Met QC Criteria: March 13, 2024
• First Posted (Actual): March 20, 2024

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 23-1044; K24DA058882 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan to share IPD.

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