Clinical trial NCT03189810: Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on Cannabis Use and Cognitive Outcomes in Schizophrenia
Official title: Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on Cannabis Use and Cognitive Outcomes in Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Repetitive Transcranial Magnetic Stimulation (rTMS)
Schizophrenia
Cannabis Use Disorder
Cognition
Keywords: Sham Repetitive Transcranial Magnetic Stimulation (rTMS)
Schizophrenia
Cannabis Use Disorder
Cognitive Function
Lead sponsor: Centre for Addiction and Mental Health
Sponsor class: OTHER
First posted: 2017-06-16
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, placebo-controlled trial
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: Weekly (Day 0, Day 7, Day 14, Day 21, Day 28) and at 8 weeks (Follow-up Day 56)
measure: 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.
timeFrame: Up to 4 weeks (Day 28) and 8 weeks (Follow-Up Day 56)
Secondary outcomes:
measure: 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.
timeFrame: Up to 4 weeks (Day 28) and 8 weeks (Follow-Up Day 56)
Other outcomes:
measure: 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).
timeFrame: Up to 4 weeks (Day 28) and 8 weeks (Follow-Up Day 56)
measure: 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).
timeFrame: Up to 4 weeks (Day 28) and 8 weeks (Follow-Up Day 56)
measure: 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).
timeFrame: Up to 4 weeks (Day 28) and 8 weeks (Follow-Up Day 56)
measure: 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).
timeFrame: Up to 4 weeks (Day 28) and 8 weeks (Follow-Up Day 56)
Locations:
city: Toronto
country: Canada
facility: Centre for Addiction and Mental Health
state: Ontario
Study officials:
affiliation: Centre for Addiction and Mental Health
name: Tony P George, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Johnstone S, Lowe DJE, Kozak-Bidzinski K, Sanches M, Castle DJ, Rabin JS, Rabin RA, George TP. Neurocognitive moderation of repetitive transcranial magnetic stimulation (rTMS) effects on cannabis use in schizophrenia: a preliminary analysis. Schizophrenia (Heidelb). 2022 Nov 17;8(1):99. doi: 10.1038/s41537-022-00303-2.