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

Обзор

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.

Вмешательства

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

Первичные конечные точки

• RsFC between the anterior cingulate cortex of the salience network and the lateral parietal cortex of the DMN [Срок оценки: From enrollment to the end of study will be up to 5 months]
• Metabolic Outcome: BMI [Срок оценки: From enrollment to the end of study will be up to 5 months]
• Metabolic Outcome: Waist Circumference [Срок оценки: From enrollment to the end of study will be up to 5 months]
• Metabolic Outcome: Glucose [Срок оценки: From enrollment to the end of study will be up to 5 months]
• Metabolic Outcome: Insulin [Срок оценки: From enrollment to the end of study will be up to 5 months]
• Metabolic Outcome: C-peptide [Срок оценки: From enrollment to the end of study will be up to 5 months]
• Metabolic Outcome: HbA1c [Срок оценки: From enrollment to the end of study will be up to 5 months]
• Metabolic Outcome: HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) [Срок оценки: From enrollment to the end of study will be up to 5 months]

Вторичные конечные точки (7)

• Antipsychotic Related Outcome: Plasma antipsychotic (haloperidol) level [Срок оценки: From enrollment to the end of study will be up to 5 months]
• Antipsychotic Related Outcome: Stanford Sleepiness Scale [Срок оценки: From enrollment to the end of study will be up to 5 months]
• Antipsychotic Related Outcome: Digit Symbol Substitution Test [Срок оценки: From enrollment to the end of study will be up to 5 months]
• Antipsychotic Related Outcome: Barnes Akathisia Scale [Срок оценки: From enrollment to the end of study will be up to 5 months]
• Antipsychotic Related Outcome: Simpson-Angus Scale [Срок оценки: From enrollment to the end of study will be up to 5 months]
• Antipsychotic Related Outcome: Abnormal Involuntary Movement Scale [Срок оценки: From enrollment to the end of study will be up to 5 months]
• Antipsychotic Related Outcome: UKU Side Effect Rating Scale [Срок оценки: From enrollment to the end of study will be up to 5 months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Четверное слепое

Основная цель

Другое

Центры проведения

Канада · 1 центр

• Centre for Addiction and Mental Health — Toronto

Идентификаторы

NCT: NCT07109245 · 2025/010

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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