Neuromodulation for Schizophrenia

Study Overview
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Brief Summary
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Our proposed study employs a novel approach to determine the clinical and functional imaging effects of brainstem neuromodulation, with an investigational study device, 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. The study device under investigation provides a safe and non-invasive method of brainstem stimulation that will be used in conjunction with a neuroimaging biomarker to measure brain changes associated with treatment and illness awareness.

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

Intervention / Treatment
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* Device: Non-invasive brainstem modulation device (stimulation Randomized)
* Device: Non-invasive brainstem modulation device (stimulation-Open Label)


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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Investigational Stimulation Pattern 1-Randomized<br> | Device: Non-invasive brainstem modulation device (stimulation Randomized)<br>* Study participants will receive  19-minute treatments twice daily in the clinic setting over 4 weeks using a non-invasive brainstem modulation device.<br>|
| Other: Investigational Stimulation Pattern 2-Randomized<br> | Device: Non-invasive brainstem modulation device (stimulation Randomized)<br>* Study participants will receive  19-minute treatments twice daily in the clinic setting over 4 weeks using a non-invasive brainstem modulation device.<br>|
| Other: Investigational Stimulation Pattern-Open Label<br> | Device: Non-invasive brainstem modulation device (stimulation-Open Label)<br>* Study participants will receive  19-minute treatments twice daily in the clinic setting over 8 weeks using a non-invasive brainstem modulation device.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Illness Awareness | functional MRI paradigm. The paradigm consists of a bank of brief questions or statements to which participants respond either yes/agree or no/disagree. The brief statements are derived from four categories: general illness awareness, symptom awareness and attribution, awareness of need for treatment, and illness independent/control. | 4 weeks from baseline to end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Examine changes in brain network activity | functional MRI blood oxygen level dependent (BOLD) in response to an illness awareness task pre- and post-treatment. This will serve as a biomarker to rigorously test whether repeated treatment engages the posterior parietal area of the brain associated with illness awareness. | 4 weeks from baseline to end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neuromodulation