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

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Psychosis; Schizo Affective Disorder; Bipolar I Disorder
• Intervention / Treatment: Drug: Intranasal Insulin

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 Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • McLean Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 36 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

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 STROOP Color-word Interference Score	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 BACS Digit Sequencing Score	Changes in BACS digit sequencing scores, ranging from 0 - 36. Higher scores indicate better cognitive function.	6 hours, pre- and post- 40 IU intranasal insulin
Changes in BACS Symbol Coding	Changes in BACS Symbol Coding test, with scores ranging from 0 - 110. Higher scores indicate better cognitive function.	6 hours, pre- and post- 40 IU intranasal insulin
Changes in BACS Verbal Fluency Scores	Changes in BACS verbal fluency subscale z-scores, measured by number of words generated over 60-second trials. A z-score of 0 indicates the population mean. 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
Change in Brain Glutamate Concentration	Changes in glutamate (Glu) concentration as measured by in vivo proton magnetic resonance spectroscopy	6 hours, pre- and post- 40 IU intranasal insulin
Changes in Brain Glutamine Concentration	Changes in glutamine (Gln) concentration as measured by in vivo proton magnetic resonance spectroscopy	6 hours, pre- and post- 40 IU intranasal insulin
Changes in Brain Glutathione Concentration	Changes in glutathione (GSH) concentration as measured by in vivo proton magnetic resonance spectroscopy	6 hours, pre- and post- 40 IU intranasal insulin

Other Outcome Measures

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

Collaborators and Investigators

• Sponsor: Mclean Hospital
• Investigators: Principal Investigator: Virginie-Anne Chouinard, M.D., McLean Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2019
• Primary Completion (Actual): February 23, 2024
• Study Completion (Actual): February 23, 2024

Study Registration Dates

• First Submitted: May 7, 2019
• First Submitted That Met QC Criteria: May 8, 2019
• First Posted (Actual): May 9, 2019

Study Record Updates

• Last Update Posted (Actual): April 15, 2025
• Last Update Submitted That Met QC Criteria: April 14, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Insulin; Psychosis; Cognition; Brain Metabolism
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders; Mood Disorders; Mental Disorders; Physiological Effects of Drugs; Hypoglycemic Agents; Insulin
• Other Study ID Numbers: 2019P000664

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes