Neuromodulation of Social Cognitive Circuitry in People With Schizophrenia Spectrum Disorders (ModSoCCS)

In this study, the investigators will be examining the effects of repetitive transcranial magnetic stimulation (rTMS) and intermittent theta burst stimulation (iTBS) on social cognitive impairments in individuals with schizophrenia spectrum disorders. Participants will be chosen by chance to receive either active rTMS stimulation, active iTBS stimulation, sham rTMS, or sham iTBS. The investigators predict that active 10Hz and iTBS stimulation will improve social cognitive impairments compared to sham stimulation. We aim to identify which type of active stimulation is most effective at inducing changes social cognition brain circuitry and secondarily which type of active stimulation is best tolerated and most effective at inducing changes in social cognitive performance.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Schizoaffective Disorder; Schizophreniform Disorders
• Intervention / Treatment: Device: Repetitive Transcranial Magnetic Stimulation; Device: Repetitive Transcranial Magnetic Stimulation (Intermittent Theta Burst Stimulation); Device: Repetitive Transcranial Magnetic Stimulation (Sham)

Detailed Description

This study is a randomized, double blind, sham controlled study which aims to use repetitive transcranial magnetic stimulation (rTMS), a form of neuromodulation, to target the neural circuitry of social cognitive (SCog) impairments in people with Schizophrenia Spectrum Disorders. We will randomize 60 people with SSDs to three groups: 20 to a conventional form of rTMS (i.e. 10 Hz rTMS); 20 to intermittent theta burst stimulation (iTBS); and 20 to either sham 10Hz rTMS stimulation or sham iTBS. We will determine whether these treatments can change the functional connectivity of key SCog brain circuits by targeting a brain region known as the dorsomedial prefrontal cortex (DMPFC). Since each person's anatomical and functional brain profile is slightly different, we will optimize the orientation and location of coil placement in each individual. Overall, our proposal follows a target engagement framework, including specifics regarding testing brain stimulation parameters (i.e., rTMS vs. iTBS) and individualizing coil placement for optimal targeting. We anticipate that active 10 Hz rTMS or iTBS will demonstrate target engagement compared to sham, and potentially ameliorate SCog deficits in people with SSDs. Our primary goal is to identify which treatment best induces change in SCog brain circuitry and secondarily which treatment is best tolerated and induces changes in social cognitive performance.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Aristotle Voineskos, MD; Phone Number: 34378 416-535-8501; Email: aristotle.voineskos@camh.ca
• Study Contact Backup: Name: Dielle Miranda, MA; Phone Number: 33120 416-535-8501; Email: dielle.miranda@camh.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • Centre for Addiction and Mental Health
• United States
  • Maryland
    • Catonsville, Maryland, United States, 21228
      • Maryland Psychiatric Research Centre
  • New York
    • Manhasset, New York, United States, 11030
      • The Feinstein Institute for Medical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-55 years;
2. Male or Female;
3. DSM-5 diagnosis of schizophrenia, schizoaffective disorder, or schizophreniform disorder; other specified psychotic disorder (documented by SCID-5);
4. Prescription of antipsychotic medication for at least 60 days and constant dose for 30 days prior to study entry (either first or second generation antipsychotics permitted);
5. Able to participate in the informed consent process and provide voluntary informed consent.

Exclusion Criteria:

1. DSM-5 substance use disorder (other than caffeine, mild cannabis use, or tobacco) within the past six months; or a positive baseline urine drug screen (except cannabis for mild use). Only participants meeting a moderate to severe cannabis use disorder will be excluded
2. Type 1 diabetes mellitus (i.e., insulin-dependent diabetes mellitus with onset < 35 years of age and/or diabetes mellitus that has been complicated by a prior documented episode of ketoacidosis)
3. Acute or unstable medical illness (e.g. delirium, cancer, uncontrolled diabetes, decompensated cardiac, hepatic, renal or pulmonary disease, stroke, or myocardial infarction), whose pathology or treatment could alter the presentation or treatment of schizophrenia or significantly increase the risk associated with the proposed treatment protocol
4. Neurological disease associated with extrapyramidal signs and symptoms (e.g. Parkinson's disease); epilepsy (i.e. seizures not due to medication/drugs or due to fever) or physical signs of stroke; any diagnosis of a Central Nervous System (CNS) disorder
5. Requires a benzodiazepine with a regular dose equivalent to lorazepam 2 mg/day or higher or any anticonvulsant due to the potential of these medications to limit the efficacy of rTMS
6. Suspected DSM-5 intellectual disability based upon clinical interview and psychosocial history or estimated IQ of <71
7. Prior Psychosurgery
8. Presence of MRI contraindications (e.g. pacemakers)
9. Pregnancy (self-report)
10. rTMS treatment in the last 5 years
11. Non-English speakers

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active 10 Hz rTMS; Active treatment will be targeted to an intensity that is 120% of the resting motor threshold. Stimulation will be delivered at 10 Hz according to conventional FDA-approved parameters (4 s on and 26 s off; 3000 pulses per session; total duration 37.5 mins) .	Device: Repetitive Transcranial Magnetic Stimulation; The present study aims to use both repetitive transcranial magnetic stimulation (rTMS) and intermittent theta burst stimulation (iTBS), safe and effective forms of neuromodulation, to target the neural circuitry of social cognitive (SCog) impairments in people with SSDs. Treatment sessions will be administered five days per week for two weeks. Other Name: MagPro X100 or R30 (Medtronic A/S. Copenhagen, Denmark) equipped with a Cool-B70 A/P coil and Qooler fluid-cooling device (MagVenture, Farum, Denmark), positioned under MRI guidance using the Brainsight neuronavigation system (Rogue Resolutions, Montreal, Canada) or Localite (Localite GmbH, Bonn, Germany)
Active Comparator: Active iTBS; Active iTBS will be targeted to an intensity that is 120% of the resting motor threshold. Stimulation will be delivered in triplet 50 Hz bursts, repeated at 5 Hz; 2 seconds on and 8 seconds off; 600 pulses per session; total duration of 3 min 9 seconds.	Device: Repetitive Transcranial Magnetic Stimulation (Intermittent Theta Burst Stimulation); The present study aims to use both repetitive transcranial magnetic stimulation (rTMS) and intermittent theta burst stimulation (iTBS), safe and effective forms of neuromodulation, to target the neural circuitry of social cognitive (SCog) impairments in people with SSDs. Treatment sessions will be administered five days per week for two weeks. Other Name: MagPro X100 or R30 (Medtronic A/S. Copenhagen, Denmark) equipped with a Cool-B70 A/P coil and Qooler fluid-cooling device (MagVenture, Farum, Denmark), positioned under MRI guidance using the Brainsight neuronavigation system (Rogue Resolutions, Montreal, Canada) or Localite (Localite GmbH, Bonn, Germany)
Sham Comparator: Sham rTMS; Sham stimulation will be delivered using the same stimulation parameters as either 10 Hz rTMS or iTBS. For both active and sham stimulation, TMS coil positioning for each individual will be optimized by combining participant fMRI data, meta-analytic functional analysis, electric field modelling, and real-time neuronavigation.	Device: Repetitive Transcranial Magnetic Stimulation (Sham); Other Name: MagPro X100 or R30(Medtronic A/S. Copenhagen, Denmark) equipped with a Cool-B70 A/P coil and Qooler fluid-cooling device (MagVenture, Farum, Denmark), positioned under MRI guidance using the Brainsight neuronavigation system (Rogue Resolutions, Montreal, Canada) or Localite (Localite GmbH, Bonn, Germany)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mentalizing brain network functional connectivity	Measured using the empathic accuracy fMRI task	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Tolerability	Measured using the Visual Analogue Scale for Pain (VAS)	2 weeks
Treatment Tolerability	Measured using proportion of participants that report headache	2 weeks
Treatment Tolerability	Measured using proportion of participants that report dizziness	2 weeks
Treatment Tolerability	Measured using proportion of treatment related SAE's	2 weeks

Collaborators and Investigators

• Sponsor: Centre for Addiction and Mental Health
• Collaborators: University of Maryland, Baltimore; National Institutes of Health (NIH); The Feinstein Institutes for Medical Research
• Investigators: Principal Investigator: Anil Malhotra, MD, The Feinstein Institute for Medical Research, Zucker Hillside Hospital; Principal Investigator: Robert Buchanan, MD, Maryland Psychiatric Research Centre, University of Maryland; Principal Investigator: Aristotle Voineskos, MD, Centre for Addiction and Mental Health

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2020
• Primary Completion (Actual): February 2, 2023
• Study Completion (Actual): February 2, 2023

Study Registration Dates

• First Submitted: May 5, 2020
• First Submitted That Met QC Criteria: June 1, 2020
• First Posted (Actual): June 5, 2020

Study Record Updates

• Last Update Posted (Actual): October 17, 2023
• Last Update Submitted That Met QC Criteria: October 16, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders
• Other Study ID Numbers: 133/2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes