Does tDCS Change Synaptic Density in the Brains of Patients With Schizophrenia

This study will examine changes in synaptic density with transcranial direct current stimulation (tDCS) in the brains of patients with schizophrenia. Synaptic density levels will be measured using a novel positron emission tomography (PET) radiotracer [18F]SDM-8, which is currently the best-in-class method to quantify synaptic density in humans. This will be a companion study to a parent study by our group examining the effects of tDCS on treatment adherence in schizophrenia (REB #103-2018).

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia; Schizoaffective
• Intervention / Treatment: Other: PET Scan

Detailed Description

The aim of our study is to examine if tDCS induces synaptic density changes in patients with schizophrenia using [18F]SDM-8. Our study will help elucidate the mechanism through which tDCS affects the brain.

PET scans will be offered to participants that meet the inclusion and exclusion criteria at the initial screening visit. Participants will be scanned with the novel PET tracer [18F]SDM-8 to quantify synaptic density levels. PET scans will be timed to coincide to the two time-points, before and after 2-weeks of tDCS treatment that is completed under the parent study protocol (REB #103-2018). Clinical assessments will be done at the same time.

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Philip Gerretsen, MD, PhD; Phone Number: 39426 416-535-8501; Email: philip.gerretsen@camh.ca
• Study Contact Backup: Name: Ariel Graff, MD, PhD; Phone Number: 34834 416-535-8501; Email: ariel.graff@camh.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 1R8
      • Recruiting
      • Centre for Addiction and Mental Health
      • Contact: Philip Gerretsen, MD, PhD; Phone Number: 39426 416-535-8501; Email: philip.gerretsen@camh.ca
      • Contact: Ariel Graff, MD, PhD; Phone Number: 34834 416-535-8501; Email: ariel.graff@camh.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants will have Schizophrenia/Schizoaffective Disorder and currently enrolled in the tDCS-adherence parent study (REB# 103-2018).

Description

Inclusion Criteria:

Enrolment in the tDCS-adherence parent study (REB# 103-2018). The parent study inclusion criteria are:

1. Male or female participants of any race or ethnicity
2. Inpatients or outpatients ≥18 years of age
3. DSM-V diagnosis of schizophrenia or schizoaffective disorder
4. Capable of consenting to participate in the research study
5. On a stable dose of oral antipsychotic drug and other concomitant medications for at least 2 months, and unlikely to undergo changes in dose during the study.

Exclusion Criteria:

The exclusion criteria for this study will be the same as the parent study (REB 103-2018). The parent study exclusion criteria are:

1. Unwilling or incapable to consent to the study based on the MacArthur Test of Competence
2. Unstable medical or any concomitant major medical or neurological illness, including a history of seizures
3. Acute suicidal or homicidal ideation
4. Formal thought disorder rating ≥3 on the Positive and Negative Syndrome Scale (PANSS) P2 conceptual disorganization item
5. DSM-V substance dependence (except caffeine, nicotine, and cannabis/marijuana) within 1 month of entering the study
6. Positive urine drug screen except for cannabis/marijuana at the screening visit
7. Metal implants or pacemaker precluding an MRI scan or other contraindications to MRI (e.g., claustrophobia)
8. Pregnancy
9. Score <32 on the Wide Range Achievement Test-III

Additional exclusion criteria for this companion study are:

1. Unwilling or incapable to consent to the study based on the MacArthur Test of Competence
2. Exposure to long-acting injectable antipsychotics in the last 6 months
3. Exceeding allowed annual radiation exposure levels (20 mSv), as outlined by our PET Centre guidelines
4. Receiving treatment with medications such as levetiracetam that blocks SV2a binding
5. Disorders of coagulation or taking anticoagulant medication
6. Having completed multiple PET scans in the past, such that participation in this study would cause participant to exceed lifetime limit (8 PET scans)

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Schizophrenia/Schizoaffective Disorder; Participants with Schizophrenia/Schizoaffective Disorder and currently enrolled in the tDCS-adherence parent study (REB# 103-2018).	Other: PET Scan; Participants will undergo two PET scans throughout the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Synaptic density changes	The primary outcome measure is the [18F]SDM-8 standard uptake value (SUV) and distribution volume ratio (DVR) in cortical and subcortical gray matter regions, measured by PET Scans	PET scans will be timed to coincide to the two time-points, before and after 2-weeks of tDCS treatment that is completed under the parent study protocol (REB #103-2018)

Collaborators and Investigators

• Sponsor: Centre for Addiction and Mental Health
• Investigators: Principal Investigator: Philip Gerretsen, MD, PhD, Centre for Addiction and Mental Health

Publications and helpful links

Helpful Links

• The Centre for Addiction and Mental Health (CAMH) is the leading mental health and addictions research facility in Canada, and one of the largest in the world.

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2021
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: June 23, 2022
• First Submitted That Met QC Criteria: June 27, 2022
• First Posted (Actual): June 28, 2022

Study Record Updates

• Last Update Posted (Actual): September 15, 2023
• Last Update Submitted That Met QC Criteria: September 14, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Positron emission tomography
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: 118/2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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