Effects of Antipsychotics on Brain Insulin Action in Females

Sponsor
Centre for Addiction and Mental Health
Study ID
NCT06251635
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
FEMALE
Age
18 Years - 35 Years
Healthy Volunteers
Accepted

Interventions

  • Olanzapine 2.5Mg Oral Tablet — DRUG
    Olanzapine capsules (2.5mg) will be administered during one research visit for each menstrual cycle phase. The dosing schedule is as follows: 1. Day 0- 5mg 2. Day 1- 10mg
  • Placebo — DRUG
    Placebo capsules visually identical to those containing olanzapine will be administered according to the same dosing schedule during one research visit of each menstrual cycle phase.
  • Insulin Lispro 100 UNT/ML — DRUG
    At each visit, participants will be given an intranasal insulin challenge (160 IU) to assess brain insulin signalling via MRI based assay.
  • Saline — DRUG
    At each visit, participants will be given an intranasal saline placebo (1.6 mL) in order to establish baseline brain insulin signalling via MRI based assay.

Study Details

Females treated with antipsychotics have higher rates of comorbid metabolic syndrome than males. Despite this, females have historically been excluded from many mechanistic studies due to confounding effects of menstrual cycles. Recent evidence suggests that brain insulin resistance may be an underlying mechanism through which antipsychotics may exert their metabolic side effects. This study seeks to investigate how brain insulin action differs in females according to their menstrual cycle phase, and how a high metabolic liability agent such as olanzapine might interrupt these differential insulin effects. Young healthy females will be given olanzapine and intranasal insulin to test how these treatment combinations change brain processes. Participants will be tested during both the first half of their menstrual cycle (follicular phase) and the second half of their cycle (luteal phase). The investigators predict that intranasal insulin will change MRI-based measures in females, in a comparable way to males, in the follicular phase only. Adding olanzapine will block these effects of insulin in females in the follicular phase. This investigation has the potential to generate new knowledge in an area of significant unmet need. Demonstrating that antipsychotics disrupt brain insulin action, evidenced by inhibition of recognized effects of insulin on neuroimaging measures, will provide novel insights into currently poorly understood mechanisms.

Key Dates

First listed
Feb 9, 2024
Start date
Jun 3, 2024
Status verified
Mar 2026
Primary completion
Aug 1, 2026
Completion
Aug 1, 2026

Study Design

Enrollment
15 participants (estimated)
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE

Arms

  • Experimental: Follicular Phase Visits
    Participants will undergo two visits during the follicular phase of the menstrual cycle (they will be scanned between day 4-10 of their menstrual cycle). Each of the study periods will involve administration of OLA 5 mg HS (or PL) on day 0, OLA 10 mg HS (or PL) on day 1, and cognitive testing and MRI scanning on day 2. MRI assessments will occur 15 minutes after administering 160 International Units (IU) INI/INP.
  • Experimental: Luteal Phase Visits
    Participants will undergo two visits during the luteal phase of the menstrual cycle (they will be scanned between day 16-22, or within 5 days of next expected menses depending on individual cycle duration). Each of the study periods will involve administration of OLA 5 mg HS (or PL) on day 0, OLA 10 mg HS (or PL) on day 1, and cognitive testing and MRI scanning on day 2. MRI assessments will occur 15 minutes after administering 160 International Units (IU) INI/INP.

Primary Outcome Measure

Resting State Functional Connectivity (assessed through Functional MRI) [ Time Frame: Visits 1-4 (5-6 months); 2 visits during follicular phase, 2 visits during luteal phase. At each visit, either oral olanzapine or placebo is given. MRI #1 occurs after intranasal challenge #1 and MRI #2 occurs after intranasal challenge #2. ]

Central Contacts

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