Exploring the role of brain insulin in cognitive and metabolic issues in schizophrenia

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

This study is testing if giving insulin through the nose can help improve thinking and metabolic problems in young adults with schizophrenia.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 17 Years to 45 Years
• Sex: All
• Sponsor: Centre for Addiction and Mental Health (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Toronto, Ontario)
• Trial ID: NCT05748990 on ClinicalTrials.gov

What this trial studies

This study investigates the relationship between abnormal insulin action in the brain and cognitive as well as metabolic dysfunctions in individuals with schizophrenia. It aims to understand how brain insulin may contribute to cognitive impairments and metabolic issues, which are prevalent in this patient population. Participants will receive either intranasal insulin or a placebo to assess its effects on cognitive and metabolic outcomes. The study focuses on individuals aged 17-45 with a diagnosis of schizophrenia spectrum disorders, particularly those who are either antipsychotic naïve or have had minimal antipsychotic treatment recently.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals aged 17-45 with a diagnosis of schizophrenia spectrum disorders who are either antipsychotic naïve or have had minimal antipsychotic treatment.

Not a fit: Patients with chronic schizophrenia who have been on antipsychotic treatment for an extended period may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to new treatment strategies that address both cognitive and metabolic dysfunctions in schizophrenia, improving patient outcomes.

How similar studies have performed: While the approach of examining brain insulin's role in schizophrenia is relatively novel, previous studies have indicated a potential link between metabolic health and cognitive function in this population.

Eligibility criteria

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.

Where this trial is running

Toronto, Ontario

• Centre for Addiction and Mental Health — Toronto, Ontario, Canada (Recruiting)

Study contacts

• Study coordinator: Mahavir Agarwal, MD, PhD

Conditions Schizophrenia; Healthy; schizophrenia; insulin; glucose; brain; PET; FDG