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Recruiting NCT07109245

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

Phase IV Interventional Brain Insulin Sensitivity Healthy Controls Cognition

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Haloperidol, Placebo, Insulin Lispro, Saline.
Who it may be relevant to
Registry conditions: Brain Insulin Sensitivity, Healthy Controls, Cognition. Basic parameters: 18 years — 35 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Canada
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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Overview

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.

Interventions

  • Drug 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.
  • Drug Placebo
    Oral placebo, encapsulated and to be taken at an equivalent titration schedule to Haloperidol.
  • 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
  • Other Saline
    A total of 1.6 mL of intranasal saline will be administered on each MRI scanning visit (0.8 mL delivered per nostril).

Primary outcome measures

  • RsFC between the anterior cingulate cortex of the salience network and the lateral parietal cortex of the DMN [Time frame: From enrollment to the end of study will be up to 5 months]
  • Metabolic Outcome: BMI [Time frame: From enrollment to the end of study will be up to 5 months]
  • Metabolic Outcome: Waist Circumference [Time frame: From enrollment to the end of study will be up to 5 months]
  • Metabolic Outcome: Glucose [Time frame: From enrollment to the end of study will be up to 5 months]
  • Metabolic Outcome: Insulin [Time frame: From enrollment to the end of study will be up to 5 months]
  • Metabolic Outcome: C-peptide [Time frame: From enrollment to the end of study will be up to 5 months]
  • Metabolic Outcome: HbA1c [Time frame: From enrollment to the end of study will be up to 5 months]
  • Metabolic Outcome: HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) [Time frame: From enrollment to the end of study will be up to 5 months]
Secondary outcome measures (7)
  • Antipsychotic Related Outcome: Plasma antipsychotic (haloperidol) level [Time frame: From enrollment to the end of study will be up to 5 months]
  • Antipsychotic Related Outcome: Stanford Sleepiness Scale [Time frame: From enrollment to the end of study will be up to 5 months]
  • Antipsychotic Related Outcome: Digit Symbol Substitution Test [Time frame: From enrollment to the end of study will be up to 5 months]
  • Antipsychotic Related Outcome: Barnes Akathisia Scale [Time frame: From enrollment to the end of study will be up to 5 months]
  • Antipsychotic Related Outcome: Simpson-Angus Scale [Time frame: From enrollment to the end of study will be up to 5 months]
  • Antipsychotic Related Outcome: Abnormal Involuntary Movement Scale [Time frame: From enrollment to the end of study will be up to 5 months]
  • Antipsychotic Related Outcome: UKU Side Effect Rating Scale [Time frame: From enrollment to the end of study will be up to 5 months]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

  • History of psychiatric illness, including any substance use (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
  • History of cell blood disorders
  • 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 \[50\]
  • Current use of progesterone, estrogen, testosterone, or fertility treatment.
  • Pregnant, gave birth in the last year, or breastfeeding. Participants must have at least 3 regular menstrual cycles post-breastfeeding before beginning the study.
  • Major medical or surgical event within the last 6 months
  • Contraindications for MRI, including metal implants, pacemakers, cochlear implants, claustrophobia, weight >250 lbs
  • 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),
  • Any medications that increases risk of hypoglycemia or could contribute to hyperglycemia
  • Any medical conditions that constitute as a warning/precaution for haloperidol, lorazepam, benztropine, or insulin.
  • 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation
Randomized
Model
Crossover
Masking
Quadruple blind
Primary purpose
Other

Study locations

Canada · 1 center
  • Centre for Addiction and Mental Health — Toronto

Identifiers

NCT: NCT07109245 · 2025/010

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗