Recruiting

Antipsychotics

Sponsor:

Centre for Addiction and Mental Health

Code:

NCT06251635

Conditions

Insulin Resistance

Menstrual Cycle

Type 2 Diabetes

Antipsychotics

Eligibility Criteria

Sex: Female

Age: 18 - 35

Healthy Volunteers: Accepted

Interventions

Olanzapine 2.5Mg Oral Tablet

Placebo

Insulin Lispro 100 UNT/ML

Saline

Study Details

Brief 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

Study ID

NCT06251635

Start date

Jun 3, 2024

Status verified date

Mar, 2026

Completion date

Aug 1, 2026

Anticipated

Primary completion date

Aug 1, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Female

Age: 18 - 35

Healthy Volunteers: Accepted

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • History of psychiatric illness (screened using the Mini International Neuropsychiatric Interview (MINI));
  • Pre-diabetes or diabetes (fasting glucose ≥6.0 mmol/L, HbA1c>6% or use of anti-diabetic drug);
  • Evidence of impaired insulin sensitivity, assessed using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) ≥2.5;
  • Family history of diabetes in a first degree relative (parent or sibling)
  • Use of weight reducing agents;
  • History of kidney or liver disease;
  • Moderate-to-severe substance use;
  • Irregular menstrual cycles (e.g., menstruation occurs less than 21 days or more than 35 days apart, or not having menstruated for three months (or 90 days), or conditions such as endometriosis or polycystic ovary syndrome (PCOS) or prior surgical interventions such as a hysterectomy or oophorectomy);
  • Current use of hormonal birth control (e.g., pill, patch, hormonal intrauterine device \[IUD\], ring). Participants must have had at least 2 regular menstrual cycles following the discontinuation of hormonal birth control;
  • Pregnant, gave birth in the last year, or breastfeeding. Participants must have at least 3 regular menstrual cycles post-breastfeeding before beginning the study;
  • Current use of progesterone, estrogen, testosterone, or fertility treatment;
  • Major medical or surgical event within the last 6 months;
  • Any condition that interferes with safe acquisition of MRI data such as metal implants, pacemakers, cochlear implants, claustrophobia, etc.
  • Any contraindications to the investigational products as listed in the product monographs including known hypersensitivity to the drug or the excipients of the product (note: enzymatic lactose intolerance is NOT exclusionary)
  • Use of any of the prohibited medications listed in the product monograph of olanzapine (e.g., Levodopa and dopamine agonists and antihypertensive agents).

Study Design

Enrollment

15 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Basic Science

Interventions and Outcome Measures

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.

Interventions

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

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.

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.

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.

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 and Locations

Central contacts

Mahavir Agarwal, MBBS, PhD

4165358501mahavir.agarwal@camh.ca

Maria Papoulias

4165358501maria.papoulias@camh.ca

Locations

Centre for Addiction and Mental Health (CAMH)

Recruiting

Toronto, Ontario, Canada, M6J 1H3

Contacts

Mahavir Agarwal, MBBS, PhD

4165358501mahavir.agarwal@camh.ca

Maria Papoulias

4165358501maria.papoulias@camh.ca

More Information

Sponsor

Centre for Addiction and Mental Health

Last update posted

Mar 31, 2026

Last verified

Mar, 2026

Keywords

  • Antipsychotics
  • Brain Insulin Resistance
  • Magnetic Resonance Imaging (MRI)
  • Metabolic Disturbances
  • Menstrual Cycle
  • Hyperinsulinemia
  • Insulin Lispro
  • Olanzapine
  • Physiological Effects of Drugs

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 2026-03-31.