Do Antipsychotics Block Insulin Action in the Brain: is it a Class Effect?
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- RsFC between the anterior cingulate cortex of the salience network and the lateral parietal cortex of the DMN
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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;
- •Body Mass Index (BMI) 18.5-24.9 kg/m2
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Saline (Other)
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.
干预措施: Haloperidol (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.
干预措施: Insulin Lispro (Drug)
Placebo
Placebo capsules, visually identical to those containing haloperidol, will be administered according to the same dosing schedule
干预措施: Placebo (Drug)
Placebo
Placebo capsules, visually identical to those containing haloperidol, will be administered according to the same dosing schedule
干预措施: Insulin Lispro (Drug)
Placebo
Placebo capsules, visually identical to those containing haloperidol, will be administered according to the same dosing schedule
干预措施: Saline (Other)
结局指标
主要结局
RsFC between the anterior cingulate cortex of the salience network and the lateral parietal cortex of the DMN
时间窗: From enrollment to the end of study will be up to 5 months
Resting state functional connectivity (rsFC) between the anterior cingulate cortex of the salience network and the lateral parietal cortex of the default mode network (DMN) will be assessed through a MRI-based assay. Calculated using the correlation between two brain regions' blood-oxygen-level-dependent (BOLD) signal times.
Metabolic Outcome: BMI
时间窗: From enrollment to the end of study will be up to 5 months
Weight (kg) and Height (cm) will be aggregated to BMI (kg/m\^2) at screening and MRI scanning visits.
Metabolic Outcome: Insulin
时间窗: From enrollment to the end of study will be up to 5 months
Insulin (uIU/mL), will be measured at screening and at 2 time points on each MRI scanning day, pre- and post-intranasal insulin challenge.
Metabolic Outcome: C-peptide
时间窗: From enrollment to the end of study will be up to 5 months
C-peptide (nmol/L), will be measured at screening and 2 time points on each MRI scanning day, pre- and post-intranasal insulin challenge.
Metabolic Outcome: HbA1c
时间窗: From enrollment to the end of study will be up to 5 months
HbA1c (mmol/mol), will be measured at screening and 2 time points on each MRI scanning day, pre- and post-intranasal insulin challenge
Metabolic Outcome: HOMA-IR (Homeostatic Model Assessment for Insulin Resistance)
时间窗: From enrollment to the end of study will be up to 5 months
HOMA-IR, will be measured at 2 time points on each MRI scanning day, pre- and post-intranasal insulin challenge. HOMA-IR = (Fasting Insulin (uIU/mL) \* Fasting Glucose (mmol/L)) / 22.5
Metabolic Outcome: Waist Circumference
时间窗: From enrollment to the end of study will be up to 5 months
Waist Circumference (cm) collected at screening and MRI scanning visits.
Metabolic Outcome: Glucose
时间窗: From enrollment to the end of study will be up to 5 months
Glucose (mmol/L), will be measured at 2 time points on each MRI scanning day, pre- and post-intranasal insulin challenge.
次要结局
- Antipsychotic Related Outcome: Plasma antipsychotic (haloperidol) level(From enrollment to the end of study will be up to 5 months)
- Antipsychotic Related Outcome: Stanford Sleepiness Scale(From enrollment to the end of study will be up to 5 months)
- Antipsychotic Related Outcome: Digit Symbol Substitution Test(From enrollment to the end of study will be up to 5 months)
- Antipsychotic Related Outcome: Barnes Akathisia Scale(From enrollment to the end of study will be up to 5 months)
- Antipsychotic Related Outcome: Simpson-Angus Scale(From enrollment to the end of study will be up to 5 months)
- Antipsychotic Related Outcome: Abnormal Involuntary Movement Scale(From enrollment to the end of study will be up to 5 months)
- Antipsychotic Related Outcome: UKU Side Effect Rating Scale(From enrollment to the end of study will be up to 5 months)