Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on Cannabis Use and Cognitive Outcomes in Schizophrenia (rTMSCANSZ)

September 1, 2023 updated by: Tony George, Centre for Addiction and Mental Health
The high prevalence of cannabis and other substance use disorders are a major barrier to recovery in people with schizophrenia. Moreover, schizophrenia patients have significant deficits in cognitive function, which may be exacerbated by cannabis use. Complicating these problems is the lack of evidence-based treatments for co-morbid cannabis use disorders (CUDs) in schizophrenia; there are no established pharmacotherapies. Therefore, this study is investigating the effects of high-frequency (20Hz) repetitive transcranial magnetic stimulation (rTMS) on cannabis use disorder and cognitive function in patients with co-morbid schizophrenia/schizoaffective disorder. The proposed study would be the first randomized, double-blind, sham controlled trial of rTMS in patients with schizophrenia and co-morbid CUD. A total of N=40 schizophrenia smokers with co-morbid cannabis use disorder will be assigned to either active rTMS (N=20) or sham rTMS (N=20) as a treatment regimen of 5X/week treatment for four consecutive weeks. All participants will receive weekly behavioral therapy for 4 weeks. The investigators predict that active rTMS will be well-tolerated and superior to sham rTMS for the treatment of CUD in schizophrenia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M6J1H4
        • Centre for Addiction and Mental Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 53 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Male (80%) or Female (20%);
  2. Age 18-55;
  3. Meet the Diagnostic and Statistical Manual of Mental Disorders version 5 (DSM-5) criteria for Schizophrenia (SZ) or schizoaffective disorder and cannabis use disorder with physiological dependence;
  4. Full scale intelligence quotient (IQ) ≥ 80 determined through the Wechsler Test of Adult Reading (WTAR);
  5. Non-smokers OR cigarette smokers as confirmed with Fragerstrom Test for Nicotine Dependence (FTND) score of 5 or higher, self reported smoking of at lest 5 cigarettes per day (measured by the Timeline Follow Back), and verified by a Smokerlyzer test, cut-off as 10 ppm.

Exclusion Criteria:

  1. DSM-5 diagnoses of alcohol, substance or polyuse substance use disorder in the past 6 months (other than cannabis/caffeine or nicotine);
  2. Currently active suicidal ideation or self-harm (suicidal or non-suicidal) as assessed by the Structured Clinical Interview for DSM-5 (SCID-5);
  3. Head injury resulting in loss of consciousness (>5 minutes) and hospitalization;
  4. Major neurological or medical illness including seizure disorder or syncope;
  5. Metallic implants;
  6. History of rTMS treatment;
  7. Pregnancy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Active rTMS (20Hz)
Active rTMS administered with the MagProX100/R30 stimulator equipped with the B65 active coil for dorsolateral prefrontal cortex (DLPFC) stimulator (MagVenture, Farum, Denmark).The randomization order will be determined by a project scientist from Temerty. While the primary aim of this study is not to treat individuals with cannabis dependence, it is imperative that participants attend weekly study visits in an attempt to achieve end of study (Day 28) cannabis abstinence.
Device: Repetitive Transcranial Magnetic Stimulation (rTMS)
On Day 1, the resting motor threshold (RMT) will be determined according to previous published methods [Cardenas-Morales et al. 2013] and the rTMS will be delivered at an intensity of 90% of the participant's RMT. rTMS will be administered at 20 Hz (25 trains, 30 pulses per train, 30 second intertrain interval).
Behavioral: Weekly Counselling Session
In order to support participants in their abstinence plan, individual weekly sessions of supportive counselling will be administered over the course of the study on 1 time per week over 4 weeks (28 days of abstinence).
Sham Comparator: Sham rTMS
Sham rTMS administered with the MagProX100/R30 stimulator equipped with the B65 placebo coil for DLPFC stimulator (MagVenture, Farum, Denmark). The randomization order will be determined by a project scientist from Temerty. While the primary aim of this study is not to treat individuals with cannabis dependence, it is imperative that participants attend weekly study visits in an attempt to achieve end of study (Day 28) cannabis abstinence.
Behavioral: Weekly Counselling Session
In order to support participants in their abstinence plan, individual weekly sessions of supportive counselling will be administered over the course of the study on 1 time per week over 4 weeks (28 days of abstinence).
Device: Sham Repetitive Transcranial Magnetic Stimulation (rTMS)
On Day 1, the resting motor threshold (RMT) will be determined according to previous published methods [Cardenas-Morales et al. 2013] and the Sham rTMS will be delivered at an intensity of 90% of the participant's RMT. rTMS will be administered at 20 Hz with the B65 placebo coil (25 trains, 30 pulses per train, 30 second intertrain interval).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The effects of active versus sham rTMS directed to DLPFC on cannabis abstinence in cannabis-dependent patients with schizophrenia as assessed by urine screens for changes in Tetrahydrocannabinol (THC) content.
Time Frame: Weekly (Day 0, Day 7, Day 14, Day 21, Day 28) and at 8 weeks (Follow-up Day 56)
Urine samples will be collected weekly during the abstinence period and tested by study personnel using the Semi-Quantitative THC Pre-Dosage Test (NarcoCheck®, Villejuif, France).
Weekly (Day 0, Day 7, Day 14, Day 21, Day 28) and at 8 weeks (Follow-up Day 56)
The effects of active versus sham rTMS directed to DLPFC on cannabis abstinence in cannabis-dependent patients with schizophrenia as assessed by urine screens for changes in Tetrahydrocannabinol (THC) content.
Time Frame: Up to 4 weeks (Day 28) and 8 weeks (Follow-Up Day 56)
Urine samples at Day 28 and Follow-Up (Day 56) will be sent to CAMH's clinical laboratory for gas chromatography/mass spectrometry (GC/MS) analysis to obtain quantitative THC-COOH and creatinine concentrations. Thus abstinence will also be assessed with combined quantitative urinalysis (<50 ng/ml) and TLFB assessment.
Up to 4 weeks (Day 28) and 8 weeks (Follow-Up Day 56)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The effects of active (20 Hz) versus sham rTMS on change in cognitive function in cannabis dependent patients with schizophrenia as assessed by a cognitive battery administered at Baseline and at Day 28.
Time Frame: Up to 4 weeks (Day 28) and 8 weeks (Follow-Up Day 56)
The cognitive battery (Day 28) will include the primary outcome of verbal memory (assessed by HVLT) and will be compared to baseline (Day 1) performance. Cortical inhibition will also be assessed and compared between Day 1 and Day 28 performance.
Up to 4 weeks (Day 28) and 8 weeks (Follow-Up Day 56)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
The effects of active (20 Hz) versus sham rTMS on change in cannabis craving in cannabis-dependent patients with schizophrenia as assessed by the Marijuana Craving Questionnaire (MCQ).
Time Frame: Up to 4 weeks (Day 28) and 8 weeks (Follow-Up Day 56)
MCQ will be assessed over time, specifically at Day 1 compared to Day 28.
Up to 4 weeks (Day 28) and 8 weeks (Follow-Up Day 56)
The effects of active (20 Hz) versus sham rTMS on change in cannabis withdrawal in cannabis-dependent patients with schizophrenia as assessed by the Marijuana Withdrawal Checklist (MWC).
Time Frame: Up to 4 weeks (Day 28) and 8 weeks (Follow-Up Day 56)
MWC will be assessed over time, specifically at Day 1 compared to Day 28.
Up to 4 weeks (Day 28) and 8 weeks (Follow-Up Day 56)
The effects of active (20 Hz) versus sham rTMS on psychotic symptoms in cannabis-dependent patients with schizophrenia as assessed by the Calgary Depression Scale for Schizophrenia (CDSS).
Time Frame: Up to 4 weeks (Day 28) and 8 weeks (Follow-Up Day 56)
CDSS scores will be compared over time, specifically Day 1 compared to Day 28. The depressive subscales within the PANSS will also be compared with the CDSS final score.
Up to 4 weeks (Day 28) and 8 weeks (Follow-Up Day 56)
The effects of active (20 Hz) versus sham rTMS on psychotic symptoms in cannabis-dependent patients with schizophrenia as assessed by the Positive and Negative Syndrome Scale (PANSS).
Time Frame: Up to 4 weeks (Day 28) and 8 weeks (Follow-Up Day 56)
PANSS will be compared over time, specifically Day 1 compared to Day 28. The depressive subscales within the PANSS will also be compared with the CDSS final score.
Up to 4 weeks (Day 28) and 8 weeks (Follow-Up Day 56)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre for Addiction and Mental Health

Investigators

  • Principal Investigator: Tony P George, MD, FRCPC, Centre for Addiction and Mental Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2017

Primary Completion (Actual)

June 30, 2021

Study Completion (Actual)

June 30, 2021

Study Registration Dates

First Submitted

May 29, 2017

First Submitted That Met QC Criteria

June 14, 2017

First Posted (Actual)

June 16, 2017

Study Record Updates

Last Update Posted (Actual)

September 5, 2023

Last Update Submitted That Met QC Criteria

September 1, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 017-2017

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

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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