Effects of Antipsychotics on Brain Insulin Action in Females
Recruiting · NCT06251635 · Interventional (participants receive a specific treatment) · Lead sponsor: Centre for Addiction and Mental Health
View the official record on ClinicalTrials.gov →Interventions studied
What this trial is about
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.
Who can take part
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).
Where it is running
1 location listed.
- Centre for Addiction and Mental Health (CAMH) - Toronto, Ontario, Canada