Clinical trial NCT04181385: Acute Olanzapine and Lipid Response
Official title: Assessment of Lipid Response to Acute Olanzapine in Healthy Adults
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Healthy
Keywords: olanzapine
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2019-11-29
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Participants receive either placebo, olanzapine or olanzapine plus bromocriptine, in random order on 3 separate study visits, with blood samples taken before and after treatment and intake of a high-fat drink
Primary purpose: BASIC_SCIENCE

Brief 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).

Detailed description: Postprandial lipid and hormonal responses are being investigated in up to 15 individuals. Participants are their own control in a single-blind, placebo-controlled, crossover design. Participants are admitted after an overnight fast. Participants will consume a high-fat drink (50g of fat) along with either oral placebo, olanzapine (10mg) or olanzapine (10mg) plus bromocriptine (5mg). Study visits occur 2-4 weeks apart with the three treatments applied in random order. Blood samples will be taken at baseline and regular intervals after the treatments for up to 8 hours to measure glucose, insulin, triglycerides, fatty acids and other hormones/metabolites.

Eligibility 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)

Primary outcomes:
measure: Plasma triglycerides
timeFrame: 8 hours
measure: Plasma fatty acids
timeFrame: 8 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Satya Dash, MD
role: PRINCIPAL_INVESTIGATOR
References: