Effects of Intranasal Insulin on Neuroimaging Markers and Cognition in Patients With Psychotic Disorders

Study Overview
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Brief Summary
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This clinical trial is a single center, single dose study of the acute effects of intranasal insulin on energy metabolism and cognitive function in patients with schizophrenia, schizoaffective and bipolar disorders, compared and healthy controls.

Detailed Description
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Psychotic disorders are common and severe psychiatric disorders. Despite advances in understanding the pathophysiology of these disorders, more effective and tolerable treatments are still needed. Evidence suggests that energy metabolism is altered in psychotic disorders. The investigators recently developed non-invasive MRI-based techniques to quantify redox balance and ATP generation in the brain. Targeting insulin pathways in the brain may allow for modulating abnormalities in energy metabolism. The investigators seek to examine whether intranasal insulin can modulate energy metabolism and improve cognition in patients with psychotic disorders. The study will use magnetic resonance spectroscopy (MRS) technology to measure in vivo energy metabolism processes in the brain, before and after the administration of intranasal insulin. Investigators will also measure changes in cognition with the administration of intranasal insulin.

Official Title
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Effects of Intranasal Insulin on Neuroimaging Markers and Cognition in Patients With Psychotic Disorders

Conditions
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Psychosis, Schizophrenia, Schizo Affective Disorder, Bipolar I Disorder

Intervention / Treatment
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* Drug: Intranasal Insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnoses of schizophrenia, schizoaffective disorder or bipolar disorder with psychotic features OR Healthy Controls (no history of DSM psychiatric diagnoses, nor history of the same in first-degree relatives) Exclusion Criteria: Psychiatric hospitalization within the last 4 weeks Unstable/active disease or potential contraindications, such as liver disease, kidney disease, uncontrolled hypertension, significant or unstable medical illness Currently prescribed: antidiabetic agents, including oral antidiabetic medications and insulin, intranasal medication, steroids, weight loss agents, protease inhibitors, or NRTI's. Pregnant or breast-feeding, not using an effective form of contraception for at least 3 months, and/or not abstinent for 1 month prior to enrollment History of significant head injury Contraindication to MRI scans (claustrophobia, cardiac pacemakers, metal clips and stents on blood vessels, artificial heart valves, artificial arms, hands, legs, etc., brain stimulator devices, implanted drug pumps, ear implants, eye implants or known metal fragments in eyes, exposure to shrapnel or metal filings, other metallic surgical hardware in vital areas, certain tattoos with metallic ink, certain transdermal patches, metal-containing IUDs). Medical conditions preventing blood draws History of electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) within the last 3 months BMI > 35 or body weight > 350 lbs or BMI <18 DSM diagnosis of substance use disorder in the past month For Healthy Controls: Taking medication other than birth control

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intranasal Insulin (40 IU)<br>40 IU Novolin-R insulin will be administered one time using the ViaNase intranasal delivery device. | Drug: Intranasal Insulin<br>* 40 units Novolin R administered intranasally using ViaNase device.<br>* Other names: Novolin R;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in brain redox state | Changes in brain NAD+/NADH ratio as measured by in vivo 31P magnetic resonance spectroscopy | 6 hours, pre- and post- 40 IU intranasal insulin | 
| Changes in brain ATP | Changes in ATP concentration as measured by in vivo 31P magnetic resonance spectroscopy | 6 hours, pre- and post- 40 IU intranasal insulin | 
| Changes in brain PCr | Changes in Phosphocreatine (PCr) concentration as measured by in vivo 31P magnetic resonance spectroscopy | 6 hours, pre- and post- 40 IU intranasal insulin | 
| Changes in brain CK | Changes in creatine kinase (CK) enzyme rate as measured by in vivo 31P magnetic resonance spectroscopy | 6 hours, pre- and post- 40 IU intranasal insulin | 
| Changes in cognitive function | Changes in STROOP assessment color-word condition interference score. This score is calculated as follows, with C being the number of items answered correctly in the color condition, W being the number answered correctly in the word condition, and CW being the number of items answered correctly in the color-word condition: CW - (C x W)/(C+W). Higher scores indicate better cognitive function. | 6 hours, pre- and post- 40 IU intranasal insulin | 
| Changes in domain-specific cognitive function. | Changes in BACS domain subscale scores (domain, range): working memory, 0-36; attention, 0-110; and verbal fluency, number of words generated over 60-sec trials. Higher scores indicate better cognitive function. | 6 hours, pre- and post- 40 IU intranasal insulin | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in brain pH. | Changes in pH as measured by in vivo 31P magnetic resonance spectroscopy | 6 hours, pre- and post- 40 IU intranasal insulin | 
| Changes in brain inorganic phosphate concentration. | Changes in inorganic phosphate (Pi) concentration as measured by in vivo 31P magnetic resonance spectroscopy | 6 hours, pre- and post- 40 IU intranasal insulin | 
| Change in fasting blood glucose levels. | Safety outcome. | 6 hours, pre- and post- 40 IU intranasal insulin | 
| Change in fasting blood insulin levels. | Safety outcome. | 6 hours, pre- and post- 40 IU intranasal insulin | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psychosis, Insulin, Brain Metabolism, Cognition