Acute Olanzapine and Lipid Response

• Status: Unknown status
• Trial end date: 2020-06-01
• Target enrollment: 0
• Participant gender: All

Summary

Atypical antipsychotics are pharmaceutical drugs used to treat schizophrenia. Common side effects are weight gain, insulin resistance, and abnormal blood lipids. This increases the risk for type 2 diabetes and cardiovascular disease in patients taking these drugs. In particular, olanzapine is a highly effective therapy for schizophrenia but is commonly associated with metabolic disturbances. It has previously been shown that the negative effects on insulin sensitivity and glucose metabolism occur even after a single dose, independently of weight gain. These effects may be mediated by blocking the dopamine (D2) receptor. In this study the research team is investigating whether a single dose of olanzapine alters postprandial lipid metabolism after a high-fat drink. Olanzapine administered along with the high-fat drink will be compared to placebo or olanzapine plus bromocriptine (an activator of the D2 receptor).

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University Health Network, Toronto
• Treatments: Bromocriptine; Olanzapine

Criteria

Inclusion Criteria:

• Men and women, aged 18 to 60 years

• Body mass index (BMI) 20 to 40 kg/m2

• Hemoglobin in the normal range.

• Normal glucose tolerance in response to a 75 gram, 2-hr oral glucose tolerance test

• Women of reproductive age should be on contraception (oral contraceptive pill or intra-uterine device/coil) for at least 2 months prior to and after the study. Anyone with a positive urine pregnancy test (carried out at screening and the day before each kinetic study) will be excluded.

Exclusion Criteria:

• Any volunteer with evidence of prolonged corrected QT interval (>470 ms in males and >450ms in females)

• Any volunteer with morbid obesity (BMI>40 or BMI>30 with any obesity related medical complication such as diabetes, hypertension or coronary disease)

• Any history of a myocardial infarction or clinically significant, active, cardiovascular history including a history of arrhythmia's or conduction delays on echocardiogram, unstable angina, or decompensated heart failure

• Study participant with a history of hepatic disease that has been active within the previous two years.

• Any current or previous history of biliary disease (including gall stones, biliary atresia and cholecystitis) or pancreatitis.

• Any current or previous history of endocrine disease, dyslipidemia or malignancy

• Any significant active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, renal (Cr > 1.5 mg/dL) genitourinary, hematological systems, or has severe uncontrolled treated or untreated hyper/ hypotension (sitting diastolic BP > 100 or systolic > 180 or systolic BP<100) or proliferative retinopathy

• Use of immunosuppressive agents at any time during the study

• Allergy to any study medication

• Pregnancy (as ascertained by urinary human chorionic gonadotropin at screening and the day before each study visit) or breastfeeding

• Fasting blood glucose > 6.0 mmol/l or known diabetes.

• Any laboratory values: aspartate aminotransferase > 2x upper limit of normal (ULN); alanine transaminase >2x ULN thyroid stimulating hormone > 6 mU/l

• Current addiction to alcohol or substances of abuse as determined by the investigator or of any mental illness.

• Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation

• Taking any regular prescription or non-prescription medications at the time of the study. Occasional use of medications such as acetaminophen or Tylenol 1 or any use of natural health products may be permitted at the discretion of the investigator.

• Will not donate blood three months prior to and three months post study procedures

• Hemoglobin below the reference range (less than 130 g/l for males and 120 g/l for females) based on blood tests at screening and on the day before the kinetic study

• Hematocrit below the reference range (less than 0.38 for males and 0.37 for females) based on blood tests at screening and on the day before the kinetic study

• Soy allergy (component of high-fat drink)