Neuromodulation of Social Cognitive Circuitry in People With Schizophrenia Spectrum Disorders

Schizophrenia Clinical Trial

— ModSoCCS  

Official title:

Neuromodulation of Social Cognitive Circuitry in People With Schizophrenia Spectrum Disorders

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04418011
• Other study ID #: 133/2019
• Status: Completed
• Phase: N/A
• Start date: November 30, 2020
• Est. completion date: February 2, 2023

Study information

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

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: February 2, 2023
• Est. primary completion date: February 2, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Psychotic Disorders
• Schizoaffective Disorder
• Schizophrenia
• Schizophreniform Disorders

Intervention

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)
• 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)
• 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)

Locations

Country	Name	City	State
Canada	Centre for Addiction and Mental Health	Toronto	Ontario
United States	Maryland Psychiatric Research Centre	Catonsville	Maryland
United States	The Feinstein Institute for Medical Research	Manhasset	New York

Sponsors (4)

Lead Sponsor	Collaborator
Centre for Addiction and Mental Health	National Institutes of Health (NIH), The Feinstein Institutes for Medical Research, University of Maryland, Baltimore

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in mentalizing brain network functional connectivity	Measured using the empathic accuracy fMRI task	2 weeks
Secondary	Treatment Tolerability	Measured using the Visual Analogue Scale for Pain (VAS)	2 weeks
Secondary	Treatment Tolerability	Measured using proportion of participants that report headache	2 weeks
Secondary	Treatment Tolerability	Measured using proportion of participants that report dizziness	2 weeks
Secondary	Treatment Tolerability	Measured using proportion of treatment related SAE's	2 weeks