The Effects of Non-invasive Neuromodulation on Illness Awareness in Schizophrenia

The Clinical and Functional Imaging Effects of Non-invasive Neuromodulation on Illness Awareness in Schizophrenia

This study aims to determine the clinical and functional imaging effects of serial CVS on illness awareness in schizophrenia. Specifically, the investigators aim to:

1. Determine if twice-daily CVS for 4 weeks will improve illness awareness compared to the sham condition in participants with schizophrenia. Illness awareness will be assessed at pre- and post-CVS, and weekly thereafter for 4 weeks.
2. Examine changes in brain network activity (blood oxygen level dependent-BOLD in response to an illness awareness task) pre- and post-CVS. This will serve as a biomarker to rigorously test whether repeated CVS engages the PPA associated with illness awareness.

Study Overview

• Status: Terminated
• Conditions: Schizophrenia; Anosognosia
• Intervention / Treatment: Device: Investigational brainstem neuromodulation device

Detailed Description

The proposed study employs a novel approach to determine the clinical and functional imaging effects of CVS on illness awareness in schizophrenia - a significant contributor to medication non-adherence and poor treatment outcomes, and arguably the most treatment resistant manifestation of the disorder. CVS is a traditionally safe and non-invasive method of vestibular stimulation that will be used in conjunction with a neuroimaging biomarker to measure brain changes associated with CVS and illness awareness. The results of this study will provide solid evidence for larger treatment-controlled effectiveness studies to determine if CVS is a practical means of producing lasting effects on illness awareness in individuals with schizophrenia or whether maintenance CVS treatment is required.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 1R8
      • Centre for Addiction and Mental Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female inpatients or outpatients ≥ 18 years of age
2. Having a DSM-V diagnosis of schizophrenia or schizoaffective disorder
3. Voluntary and capable of consenting to participation in the research study
4. Fluent in English
5. Moderate-to-severe lack of illness awareness ≤7 on the VAGUS-SR, which corresponds to a rating of ≥3 on PANSS G12 Insight and Judgment item)
6. On a stable dose of antipsychotic and other concomitant medications for at least 2 months, and unlikely to undergo changes in dose during the study

Exclusion Criteria:

1. Unwilling or unable to consent to the study
2. Use of hearing aids or cochlear implants, chronic tinnitus, temporomandibular joint disease
3. Had eye surgery within the previous three (3) months
4. Ear surgery within 6 months prior to entering the study
5. Active ear infection or perforated tympanic membrane
6. Diagnosis of vestibular dysfunction
7. Unstable medical illness or any concomitant major medical or neurological illness, including a history of cardiovascular disease and seizures
8. Acute suicidal and/or homicidal ideation
9. Formal thought disorder rating ≥4 on PANSS item P2
10. DSM-V substance dependence (except caffeine and nicotine) within one month prior to entering the study
11. Positive urine drug screen at the screening visit
12. Metal implants or a pacemaker that would preclude the MRI scan
13. Pregnancy

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 Treatment; Study participants will receive ~18-minute active stimulation twice daily over 4 weeks, using a non-invasive brainstem modulation device.	Device: Investigational brainstem neuromodulation device; This study device is non-invasive meaning it stays outside of the body. It stimulates activity in the brain through a headset with metallic earpieces that fit into the participant's ear canals. The device will be loaded with certain neurostimulation pattern, and the earpieces will provide the stimulation at the prescribed pattern.
Placebo Comparator: Sham Treatment; Study participants will receive ~18-minute of sham stimulation twice daily over 4 weeks using a non-invasive brainstem modulation device.	Device: Investigational brainstem neuromodulation device; This study device is non-invasive meaning it stays outside of the body. It stimulates activity in the brain through a headset with metallic earpieces that fit into the participant's ear canals. The device will be loaded with certain neurostimulation pattern, and the earpieces will provide the stimulation at the prescribed pattern.
Experimental: Open Label; After completion of sham or active stimulation over 4 weeks, participants can choose to receive ~18-minute active stimulation twice daily for up to 12 weeks.	Device: Investigational brainstem neuromodulation device; This study device is non-invasive meaning it stays outside of the body. It stimulates activity in the brain through a headset with metallic earpieces that fit into the participant's ear canals. The device will be loaded with certain neurostimulation pattern, and the earpieces will provide the stimulation at the prescribed pattern.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Illness awareness	Changes in illness awareness will be assessed using questionnaires.	Illness awareness will be assessed at pre-intervention and immediately following the intervention and weekly for up to 4 weeks post-intervention.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain network activity	Assess changes in brain network activity (blood oxygen level dependent-BOLD in response to an illness awareness task)	At baseline and post-intervention.

Collaborators and Investigators

• Sponsor: Centre for Addiction and Mental Health
• Collaborators: Scion NeuroStim
• 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 12, 2023
• Primary Completion (Actual): February 11, 2025
• Study Completion (Actual): February 11, 2025

Study Registration Dates

• First Submitted: June 13, 2023
• First Submitted That Met QC Criteria: July 20, 2023
• First Posted (Actual): July 24, 2023

Study Record Updates

• Last Update Posted (Actual): March 28, 2025
• Last Update Submitted That Met QC Criteria: March 25, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Magnetic resonance imaging; Medical device; Non-invasive neuromodulation; Illness awareness
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Neurobehavioral Manifestations; Perceptual Disorders; Schizophrenia; Agnosia
• Other Study ID Numbers: 105-2017

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: Yes
• product manufactured in and exported from the U.S.: Yes