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

Schizophrenia Clinical Trial

— rTMSCANSZ  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03189810
• Other study ID #: 017-2017
• Status: Completed
• Phase: N/A
• Start date: June 1, 2017
• Est. completion date: June 30, 2021

Study information

• Verified date: September 2023
• Source: Centre for Addiction and Mental Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: June 30, 2021
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cannabis Use Disorder
• Cognition
• Marijuana Abuse
• Repetitive Transcranial Magnetic Stimulation (rTMS)
• Schizophrenia

Intervention

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).
• 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).

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).

Locations

Country	Name	City	State
Canada	Centre for Addiction and Mental Health	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Centre for Addiction and Mental Health

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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).	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)
Other	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).	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)
Other	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).	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)
Other	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).	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)
Primary	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.	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)
Primary	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.	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	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.	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)