Clinical trial NCT04418011: Neuromodulation of Social Cognitive Circuitry in People With Schizophrenia Spectrum Disorders
Official title: Neuromodulation of Social Cognitive Circuitry in People With Schizophrenia Spectrum Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Schizophrenia
Schizoaffective Disorder
Schizophreniform Disorders
Lead sponsor: Centre for Addiction and Mental Health
Sponsor class: OTHER
Collaborators: name: Northwell Health
name: University of Maryland, Baltimore
name: National Institutes of Health (NIH)
First posted: 2020-06-05
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in mentalizing brain network functional connectivity
timeFrame: 2 weeks
Secondary outcomes:
measure: Treatment Tolerability
timeFrame: 2 weeks
measure: Treatment Tolerability
timeFrame: 2 weeks
measure: Treatment Tolerability
timeFrame: 2 weeks
measure: Treatment Tolerability
timeFrame: 2 weeks
Other outcomes:
Locations:
city: Catonsville
country: United States
facility: Maryland Psychiatric Research Centre
state: Maryland
city: Manhasset
country: United States
facility: The Feinstein Institute for Medical Research
state: New York
city: Toronto
country: Canada
facility: Centre for Addiction and Mental Health
state: Ontario
Study officials:
affiliation: Centre for Addiction and Mental Health
name: Aristotle Voineskos, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Feinstein Institute for Medical Research, Zucker Hillside Hospital
name: Anil Malhotra, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Maryland Psychiatric Research Centre, University of Maryland
name: Robert Buchanan, MD
role: PRINCIPAL_INVESTIGATOR
References: