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

NCT ID: NCT07109245

Last Updated: 2025-08-07

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-01
• Study Completion Date: 2028-12-31

Brief Summary

This study aimed at helping researchers understand how a medication called haloperidol can affect insulin action in the brain. Insulin is a hormone in the body that controls sugar levels in part by lowering the amount of glucose produced by the liver. After eating a meal, insulin levels go up in both the blood and the brain. Insulin in the brain has also been shown to affect the way the brain works and processes information (also known as "cognition"). Haloperidol, is an antipsychotic medication used to treat a variety of disorders such as schizophrenia spectrum disorders, bipolar disorder, and major depressive disorder, but long-term use can have metabolic side effects, like weight gain, type 2 diabetes, and cardiovascular disease. The purpose of this study is to investigate how antipsychotic medications, such as haloperidol, which carries the risk of metabolic changes, might interrupt the effect of insulin action in the brain. This will help researchers learn how to potentially reduce metabolic risk for people who take these kinds of medications in the future.

Conditions

Brain Insulin Sensitivity; Healthy Controls; Cognition

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

Haloperidol

The oral investigational agent haloperidol (Generic Brand: TEVA-HALOPERIDOL) will be self-administered, at night, over 7 days. Haloperidol will be titrated up to 2 mg.

Group Type: EXPERIMENTAL

Haloperidol

Intervention Type: DRUG

The oral investigational agent haloperidol (Generic Brand: TEVA-HALOPERIDOL) will be self-administered, at night, over 7 days. Haloperidol will be titrated up to 2 mg.

Insulin Lispro

Intervention Type: DRUG

A total of 160 IU of intransal insulin (=1.6 mL) will be administered on MRI scanning visits (80 IU = 0.8 mL delivered per nostril). Humalog; Eli Lilly Canada

Saline

Intervention Type: OTHER

A total of 1.6 mL of intranasal saline will be administered on each MRI scanning visit (0.8 mL delivered per nostril).

Placebo

Placebo capsules, visually identical to those containing haloperidol, will be administered according to the same dosing schedule

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Oral placebo, encapsulated and to be taken at an equivalent titration schedule to Haloperidol.

Insulin Lispro

Intervention Type: DRUG

A total of 160 IU of intransal insulin (=1.6 mL) will be administered on MRI scanning visits (80 IU = 0.8 mL delivered per nostril). Humalog; Eli Lilly Canada

Saline

Intervention Type: OTHER

A total of 1.6 mL of intranasal saline will be administered on each MRI scanning visit (0.8 mL delivered per nostril).

Interventions

Haloperidol

The oral investigational agent haloperidol (Generic Brand: TEVA-HALOPERIDOL) will be self-administered, at night, over 7 days. Haloperidol will be titrated up to 2 mg.

Intervention Type: DRUG

Placebo

Oral placebo, encapsulated and to be taken at an equivalent titration schedule to Haloperidol.

Intervention Type: DRUG

Insulin Lispro

A total of 160 IU of intransal insulin (=1.6 mL) will be administered on MRI scanning visits (80 IU = 0.8 mL delivered per nostril). Humalog; Eli Lilly Canada

Intervention Type: DRUG

Saline

A total of 1.6 mL of intranasal saline will be administered on each MRI scanning visit (0.8 mL delivered per nostril).

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

The Physicians' Services Incorporated Foundation

OTHER

Sponsor Role: collaborator

Centre for Addiction and Mental Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mahavir Agarwal, MBBS, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Centre for Addiction and Mental Health

Locations

Centre for Addiction and Mental Health

Toronto, Ontario, Canada

Countries

Canada

Central Contacts

Mahavir Agarwal, MBBS, MD, PhD

Role: CONTACT

mahavir.agarwal@camh.ca

416-535-8501 ext. 30546

Maria Papoulias, MSc

Role: CONTACT

maria.papoulias@camh.ca

416-535-8501 ext. 39365

Facility Contacts

Mahavir Agarwal, MBBS, MD, PhD

Role: primary

mahavir.agarwal@camh.ca

416-535-8501 ext. 30546

Other Identifiers

2025/010

Identifier Type: -

Identifier Source: org_study_id