Acute Olanzapine and Lipid Response (OLA)

Assessment of Lipid Response to Acute Olanzapine in Healthy Adults

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).

Study Overview

• Status: Unknown
• Conditions: Healthy
• Intervention / Treatment: Drug: Olanzapine 10 milligram; Drug: Bromocriptine 5 milligram; Drug: Placebo oral tablet

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.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Recruiting
      • Toronto General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Olanzapine; Olanzapine, 10mg, oral, single dose	Drug: Olanzapine 10 milligram; Oral olanzapine capsule
EXPERIMENTAL: Olanzapine plus bromocriptine; Olanzapine, 10mg, oral, single dose Bromocriptine, 5mg, oral, single dose	Drug: Olanzapine 10 milligram; Oral olanzapine capsule; Drug: Bromocriptine 5 milligram; Oral bromocriptine capsule
PLACEBO_COMPARATOR: Placebo; Placebo, oral, single dose	Drug: Placebo oral tablet; oral placebo capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma triglycerides	Plasma triglycerides measured after treatments	8 hours
Plasma fatty acids	Plasma fatty acids measured after treatments	8 hours

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Satya Dash, MD, University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2019
• Primary Completion (ANTICIPATED): January 1, 2020
• Study Completion (ANTICIPATED): June 1, 2020

Study Registration Dates

• First Submitted: November 25, 2019
• First Submitted That Met QC Criteria: November 26, 2019
• First Posted (ACTUAL): November 29, 2019

Study Record Updates

• Last Update Posted (ACTUAL): December 3, 2019
• Last Update Submitted That Met QC Criteria: December 2, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: olanzapine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Dopamine Agonists; Dopamine Agents; Hormone Antagonists; Antiparkinson Agents; Anti-Dyskinesia Agents; Olanzapine; Bromocriptine
• Other Study ID Numbers: OLA 15-8951

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No