Effects of Antipsychotics on Brain Insulin Action in Females: A Randomised Placebo-Controlled, Crossover Multi-Modal Neuroimaging Study

Status: Recruiting
Location: See location...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Not Applicable
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.

Eligibility
Participation Requirements
Sex: Female
Minimum Age: 18
Maximum Age: 35
Healthy Volunteers: t
View:

• Age: 18-35 years

• Body Mass Index (BMI) between 18.5 - 24.9 kg/m2

• Normal menstrual cycle (defined as cycle length ranging from 21 to 35 days over the past 6 months).

Locations
Other Locations
Canada
Centre for Addiction and Mental Health (CAMH)
RECRUITING
Toronto
Contact Information
Primary
Mahavir Agarwal, MBBS, PhD
mahavir.agarwal@camh.ca
4165358501
Backup
Maria Papoulias
maria.papoulias@camh.ca
4165358501
Time Frame
Start Date: 2024-06-03
Estimated Completion Date: 2026-03-01
Participants
Target number of participants: 15
Treatments
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.
Sponsors
Leads: Centre for Addiction and Mental Health

This content was sourced from clinicaltrials.gov