Do antipsychotic drugs block insulin action in the brain?

Do Antipsychotics Block Insulin Action in the Brain: is it a Class Effect?

This project will test whether haloperidol blocks insulin action in the brain of healthy adults aged 18–35.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 35 (estimated)
• Ages: 18 Years to 35 Years
• Sex: All
• Sponsor: Centre for Addiction and Mental Health (Academic / other)
• Locations: 1 site (Toronto, Ontario)
• Trial ID: NCT07109245 on ClinicalTrials.gov

What this trial studies

This Phase 4 interventional study enrolls healthy 18–35-year-old adults with normal BMI and no psychiatric or metabolic disorders. Participants receive pharmacologic challenges with haloperidol or placebo and with insulin lispro or saline while investigators measure brain responses and cognition using MRI and cognitive tests. The design compares brain insulin signaling and cognitive effects after antipsychotic versus placebo exposure to see if haloperidol interferes with insulin action in the brain. Strict metabolic and psychiatric exclusion criteria are used to isolate drug effects in metabolically healthy volunteers.

Who should consider this trial

Good fit: Healthy adults aged 18–35 with BMI 18.5–24.9, normal glucose metabolism and insulin sensitivity, no psychiatric history, and ability to consent are ideal candidates.

Not a fit: People with psychiatric disorders, diabetes or prediabetes, impaired insulin sensitivity, a family history of diabetes, or outside the specified age/BMI ranges are not eligible and are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the results could clarify whether antipsychotics impair brain insulin signaling and inform strategies to reduce metabolic and cognitive side effects in patients on these drugs.

How similar studies have performed: Prior research has linked antipsychotics to systemic metabolic side effects and altered cognition, but direct effects of haloperidol on brain insulin signaling remain relatively novel and not well-established.

Eligibility criteria

Inclusion Criteria:

1. Must be deemed to have the capacity to provide informed consent
2. Must sign and date the informed consent form
3. Stated willingness to comply with all study procedures;
4. Age: 18-35
5. Body Mass Index (BMI) 18.5-24.9 kg/m2
6. Both sexes

Exclusion Criteria:

1. History of psychiatric illness, including any substance use (screened using the Mini International Neuropsychiatric Interview (MINI))
2. Pre-diabetes or diabetes (fasting glucose ≥6.0 mmol/L, HbA1c\>6% or use of anti-diabetic drug),
3. Evidence of impaired insulin sensitivity, assessed using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) ≥2.5
4. Family history of diabetes in a first degree relative (parent or sibling)
5. Use of weight reducing agents
6. History of kidney or liver disease
7. History of cell blood disorders
8. 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)
9. 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 \[50\]
10. Current use of progesterone, estrogen, testosterone, or fertility treatment.
11. Pregnant, gave birth in the last year, or breastfeeding. Participants must have at least 3 regular menstrual cycles post-breastfeeding before beginning the study.
12. Major medical or surgical event within the last 6 months
13. Contraindications for MRI, including metal implants, pacemakers, cochlear implants, claustrophobia, weight \>250 lbs
14. 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),
15. Any medications that increases risk of hypoglycemia or could contribute to hyperglycemia
16. Any medical conditions that constitute as a warning/precaution for haloperidol, lorazepam, benztropine, or insulin.
17. Use of any of the prohibited medications listed in the product monograph of haloperidol, lorazepam, benztropine, or insulin (Pheochromocytoma, barbiturates, and narcotics are exclusionary, any use of painkillers and antihistamines must be reviewed by PI but are not exclusionary

Where this trial is running

Toronto, Ontario

• Centre for Addiction and Mental Health — Toronto, Ontario, Canada (Recruiting)

Study contacts

• Principal investigator: Mahavir Agarwal, MBBS, MD, PhD — Centre for Addiction and Mental Health
• Study coordinator: Mahavir Agarwal, MBBS, MD, PhD

Conditions Brain Insulin Sensitivity; Healthy Controls; Cognition; Healthy Control Study; Haloperidol; MRI