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

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

Detailed Description
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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.

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

Conditions
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Schizophrenia, Anosognosia

Intervention / Treatment
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* Device: Investigational brainstem neuromodulation device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female inpatients or outpatients ≥ 18 years of age Having a DSM-V diagnosis of schizophrenia or schizoaffective disorder Voluntary and capable of consenting to participation in the research study Fluent in English 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) 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: Unwilling or unable to consent to the study Use of hearing aids or cochlear implants, chronic tinnitus, temporomandibular joint disease Had eye surgery within the previous three (3) months Ear surgery within 6 months prior to entering the study Active ear infection or perforated tympanic membrane Diagnosis of vestibular dysfunction Unstable medical illness or any concomitant major medical or neurological illness, including a history of cardiovascular disease and seizures Acute suicidal and/or homicidal ideation Formal thought disorder rating ≥4 on PANSS item P2 DSM-V substance dependence (except caffeine and nicotine) within one month prior to entering the study Positive urine drug screen at the screening visit Metal implants or a pacemaker that would preclude the MRI scan Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Treatment<br>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<br>* 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.<br>|
| Placebo Comparator: Sham Treatment<br>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<br>* 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.<br>|
| Experimental: Open Label<br>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<br>* 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.<br>|

What is the study measuring?
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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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-invasive neuromodulation, Illness awareness, Magnetic resonance imaging, Medical device