Recruiting

Observational Study

Sponsor:

Centre for Addiction and Mental Health

Code:

NCT05748990

Conditions

Schizophrenia

Healthy

Eligibility Criteria

Sex: All

Age: 17 - 45

Healthy Volunteers: Accepted

Interventions

Intranasal insulin

Placebo

Study Details

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

Study ID

NCT05748990

Start date

Apr 1, 2023

Status verified date

May, 2026

Completion date

Aug 1, 2026

Anticipated

Primary completion date

Aug 1, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 17 - 45

Healthy Volunteers: Accepted

Inclusion Criteria:

i) Experimental group (participants with a diagnosis of schizophrenia spectrum disorder):

1. 17-45 years
2. both sexes;
3. 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).
4. BMI under or equal to 27

ii) Control group (healthy controls):

1. 17-45 years of age
2. sex-,
3. hand dominance -and
4. body mass index (BMI)-matched
5. Absence of DSM-5 diagnosis other than a specific phobia according to MINI

Exclusion Criteria:

1. moderate or severe substance use according to MINI (per PI discretion in the case of moderate alcohol or cannabis use)
2. prediabetes, diabetes, or evidence of impaired glucose tolerance on screening OGTT
3. acute suicidal risk
4. use of weight, lipid, antidiabetic or blood pressure reducing agents
5. liver or kidney disease
6. pregnancy
7. nursing
8. pacemakers
9. metallic cardiac valves
10. magnetic material such as surgical clips, implanted electronic infusion pumps or any other conditions that would preclude the MRI scan
11. clinically significant claustrophobia (determined from MRI screening form; significance evaluated as per QI's discretion).
12. history of head trauma resulting in loss of consciousness > 30 minutes that required medical attention;
13. size of head, neck, precluding to fit in the MRI or PET scanners
14. weight over 350lbs (limit for MRI scanner bed)
15. unstable physical illness
16. significant neurological disorder including a seizure disorder;
17. Received maximum allowed radiation in the past 12 months (20 mSv)
18. Completed more than 6 PET scans/ lifetime, that, together with the PET scanning procedures under this protocol will bring the total number of PET scans to more than the allowed/lifetime (8 PET scans per lifetime). These limits are set by the Centre for Addiction and Mental Health Brain Health Imaging Centre Guideline.
19. clinically relevant abnormality observed in medical history,
20. current intake of any medication that may interfere with participation in the study or may confound the results of PET imaging (e.g. anti-diabetic medication).
21. Disorders of coagulation, blood or ongoing use of anticoagulant medication

Control group: Exclusionary criteria are as listed above for participants, in addition to:

1\) First degree family member with primary psychotic disorder.

Study Design

Enrollment

20 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: Schizophrenia Group

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

experimental: Healthy Control Group

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

Interventions

Intranasal insulin

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

Placebo

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

Primary outcome measure

  • [18F]-FDG brain uptake [ Time Frame: Scan duration is ~90 minutes ]

Central Contacts and Locations

Central contacts

Locations

Centre for Addiction and Mental Health

Recruiting

Toronto, Ontario, Canada, M6J1H3

Contacts

Principal Investigator:

Mahavir Agarwal, PhD, MBBS, MD

More Information

Sponsor

Centre for Addiction and Mental Health

Last update posted

May 28, 2026

Last verified

May, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Centre for Addiction and Mental Health on 2026-05-28.