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

Sponsor

Mclean Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT03943537

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Psychosis Schizophrenia Schizo Affective Disorder Bipolar I Disorder	Drug: Intranasal Insulin	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

Oct 1, 2019

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intranasal Insulin (40 IU) 40 IU Novolin-R insulin will be administered one time using the ViaNase intranasal delivery device.	Drug: Intranasal Insulin 40 units Novolin R administered intranasally using ViaNase device. Other Names: Novolin R

Arm

Intervention/Treatment

Experimental: Intranasal Insulin (40 IU)

40 IU Novolin-R insulin will be administered one time using the ViaNase intranasal delivery device.

Drug: Intranasal Insulin

40 units Novolin R administered intranasally using ViaNase device.

Other Names:

Novolin R

Outcome Measures

Primary Outcome Measures

Changes in brain redox state [6 hours, pre- and post- 40 IU intranasal insulin]
Changes in brain NAD+/NADH ratio as measured by in vivo 31P magnetic resonance spectroscopy
Changes in brain ATP [6 hours, pre- and post- 40 IU intranasal insulin]
Changes in ATP concentration as measured by in vivo 31P magnetic resonance spectroscopy
Changes in brain PCr [6 hours, pre- and post- 40 IU intranasal insulin]
Changes in Phosphocreatine (PCr) concentration as measured by in vivo 31P magnetic resonance spectroscopy
Changes in brain CK [6 hours, pre- and post- 40 IU intranasal insulin]
Changes in creatine kinase (CK) enzyme rate as measured by in vivo 31P magnetic resonance spectroscopy
Changes in cognitive function [6 hours, pre- and post- 40 IU intranasal insulin]
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.
Changes in domain-specific cognitive function. [6 hours, pre- and post- 40 IU intranasal insulin]
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.

Secondary Outcome Measures

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

Other Outcome Measures

Changes in brain Gln, Glu and GSH [6 hours, pre- and post- 40 IU intranasal insulin]
Changes in glutamine (Gln), glutamate (Glu), and glutathione (GSH) concentration as measured by in vivo proton magnetic resonance spectroscopy

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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) within the last 6 months
BMI > 35 or body weight > 350 lbs or BMI <18
DSM diagnosis of substance use disorder in the past 3 months
For Healthy Controls:
Taking medication other than birth control