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

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ClinicalTrials.gov Identifier: NCT03189810
Recruitment Status : Recruiting
First Posted : June 16, 2017
Last Update Posted : July 27, 2018
Sponsor:
Information provided by (Responsible Party):
Tony George, Centre for Addiction and Mental Health

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.

Condition or disease Intervention/treatment Phase
Repetitive Transcranial Magnetic Stimulation (rTMS) Schizophrenia Cannabis Use Disorder Cognition Device: Repetitive Transcranial Magnetic Stimulation (rTMS) Device: Sham Repetitive Transcranial Magnetic Stimulation (rTMS) Behavioral: Weekly Counselling Session Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double-blind, placebo-controlled trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: The rTMS technicians, participants, research analysts and investigators involved in the study will be blind to the rTMS treatment assignment.
Primary Purpose: Treatment
Official Title: Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on Cannabis Use and Cognitive Outcomes in Schizophrenia
Actual Study Start Date : June 1, 2017
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2021

Resource links provided by the National Library of Medicine


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.
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).

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).




Primary Outcome Measures :
  1. 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).

  2. 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.


Secondary Outcome Measures :
  1. 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.


Other Outcome Measures:
  1. 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.

  2. 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.

  3. 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.

  4. 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.



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03189810


Contacts
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Contact: Karolina Kozak, MSc 416-535-8501 ext 30463 karolina.kozak@camh.ca

Locations
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Canada, Ontario
Centre for Addiction and Mental Health Recruiting
Toronto, Ontario, Canada, M6J1H4
Contact: Tony P George, MD, FRCPC    416-535-8501 ext 32662    tony.george@camh.ca   
Principal Investigator: Tony P George, MD, FRCPC         
Sponsors and Collaborators
Centre for Addiction and Mental Health
Investigators
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Principal Investigator: Tony P George, MD, FRCPC Centre for Addiction and Mental Health

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Responsible Party: Tony George, Principal Investigator, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier: NCT03189810     History of Changes
Other Study ID Numbers: 017-2017
First Posted: June 16, 2017    Key Record Dates
Last Update Posted: July 27, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tony George, Centre for Addiction and Mental Health:
Sham Repetitive Transcranial Magnetic Stimulation (rTMS)
Schizophrenia
Cannabis Use Disorder
Cognitive Function
Additional relevant MeSH terms:
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Marijuana Abuse
Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Substance-Related Disorders
Chemically-Induced Disorders