Effects of Antipsychotics on Brain Insulin Action in Females

Summary

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.

Conditions

• Insulin Resistance
• Menstrual Cycle
• Type 2 Diabetes
• Antipsychotics

Interventions

DRUG

Olanzapine 2.5Mg Oral Tablet

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

DRUG

Placebo

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.

DRUG

Insulin Lispro 100 UNT/ML

At each visit, participants will be given an intranasal insulin challenge (160 IU) to assess brain insulin signalling via MRI based assay.

DRUG

Saline

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.

Sponsors & Collaborators

• Centre for Addiction and Mental Health

  lead OTHER

Principal Investigators

• Mahavir Agarwal, MBBS, PhD, MD · Centre for Addiction and Mental Health

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

35 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2024-06-03

Primary Completion

2026-08-01

Completion

2026-08-01

Countries

• Canada

Study Locations