Does Abnormal Insulin Action in the Brain Underlie Cognitive and Metabolic Dysfunction in Schizophrenia

NCT05748990 | Recruiting

• 1 other identifier: 154-2020
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Cognitive impairment (such as challenges in thinking and memory) is a core aspect of schizophrenia (SCZ), contributing to disability and poor functional outcomes. Additionally, almost half of the patients with SCZ are obese, the prevalence of type 2 diabetes is 3-6 times higher, and life expectancy is lower by 15-20 years compared to the general population. This is relevant as metabolic syndrome and diabetes are both associated with worse cognition among SCZ patients. Recent work studying the relationships between metabolic health and cognition has encouraged a new way of thinking about SCZ as both a metabolic and cognitive disorder. Brain insulin is involved in several processes relevant to SCZ, and abnormal brain insulin action may help explain both cognitive and metabolic abnormalities in patients with SCZ, but this has not been examined previously. Glucose uptake in several brain regions relevant to SCZ has been shown to be partially dependent on insulin. Therefore, in this study, the researchers will measure glucose uptake in the brain using an 18F-fluorodeoxyglucose (\[18F\]-FDG) positron emission tomography (PET) scan after an intranasal insulin stimulus, and will compare this measure between patients with SCZ and healthy controls.

Conditions

Schizophrenia; Healthy

Keywords

schizophrenia; insulin; glucose; brain; PET; FDG; antipsychotic-naive; 18-fluorodeoxyglucose; intranasal insulin

Outcome Measures

Primary Outcomes (1)

• [18F]-FDG brain uptake

  Change in \[18F\]-FDG uptake in striatum and hippocampus is measured in response to intranasal insulin challenge or placebo

  Scan duration is ~90 minutes

Study Arms (2)

Schizophrenia Group

EXPERIMENTAL

Insulin (160IU) or placebo is administered intranasally 15 minutes prior to the PET scan.

Drug: Intranasal insulin; Drug: Placebo

Healthy Control Group

EXPERIMENTAL

Insulin (160 IU) or placebo is administered intranasally 15 minutes prior to the PET scan.

Drug: Intranasal insulin; Drug: Placebo

Interventions

Intranasal insulin DRUG

160 IU insulin (Humalog) is administered intranasally using a metered spray bottle 15 minutes prior to the PET scan.

Also known as: Humalog

Healthy Control Group; Schizophrenia Group

Placebo DRUG

0.9% saline is administered intranasally using a metered spray bottle 15 minutes prior to the PET scan.

Also known as: saline

Healthy Control Group; Schizophrenia Group

Eligibility Criteria

• Age: 17 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• i) Experimental group (participants with a diagnosis of schizophrenia spectrum disorder):
• years
• both sexes;
• Patients with first-episode schizophrenia spectrum illness: Primary DSM-5 diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, brief psychotic disorder, psychotic disorder NOS, major depressive disorder with psychotic symptoms, bipolar I disorder, and bipolar II disorder, OR substance-induced psychosis, and antipsychotic treatment for schizophrenia, schizoaffective disorder, or other specified schizophrenia spectrum, other psychotic disorder, major depressive disorder with psychotic symptoms, bipolar I disorder, and bipolar II. (Diagnosis willbe confirmed via CAMH chart review).
• BMI under or equal to 27
• ii) Control group (healthy controls):
• years of age
• sex-,
• hand dominance -and
• body mass index (BMI)-matched
• Absence of DSM-5 diagnosis other than a specific phobia according to MINI

You may not qualify if:

• moderate or severe substance use according to MINI (per PI discretion in the case of moderate alcohol or cannabis use)
• prediabetes, diabetes, or evidence of impaired glucose tolerance on screening OGTT
• acute suicidal risk
• use of weight, lipid, antidiabetic or blood pressure reducing agents
• liver or kidney disease
• pregnancy
• nursing
• pacemakers
• metallic cardiac valves
• magnetic material such as surgical clips, implanted electronic infusion pumps or any other conditions that would preclude the MRI scan
• clinically significant claustrophobia (determined from MRI screening form; significance evaluated as per QI's discretion).
• history of head trauma resulting in loss of consciousness \> 30 minutes that required medical attention;
• size of head, neck, precluding to fit in the MRI or PET scanners
• weight over 350lbs (limit for MRI scanner bed)
• unstable physical illness

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M6J1H3, Canada

RECRUITING

MeSH Terms

Conditions

Schizophrenia; Insulin Resistance

Interventions

Insulin Lispro; Sodium Chloride

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Insulin, Short-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Central Study Contacts

Mahavir Agarwal, MD, PhD

CONTACT

416-535-8501; mahavir.agarwal@camh.ca

Laurie Hamel, MA

CONTACT

416-535-8501; laurie.hamel@camh.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: In a single-blind crossover design, participants will undergo an \[18F\]-FDG PET scan on 2 separate occasions separated by 4-7 days. One of the PET scans will be following intranasal placebo (saline) and the other will follow an intranasal insulin challenge (160 IU). The scans will be conducted in a randomized counterbalanced order across participants to account for exposure to antipsychotics between the two scans.

Study Record Dates

• First Submitted: February 18, 2023
• First Posted: March 1, 2023
• Study Start: April 1, 2023
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: August 5, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)