Acute Olanzapine and Lipid Response

NCT04181385 | Unknown Phase 2

• 1 other identifier: OLA 15-8951
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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).

Conditions

Healthy

Keywords

olanzapine

Outcome Measures

Primary Outcomes (2)

• Plasma triglycerides

  Plasma triglycerides measured after treatments

  8 hours

• Plasma fatty acids

  Plasma fatty acids measured after treatments

  8 hours

Study Arms (3)

Olanzapine

EXPERIMENTAL

Olanzapine, 10mg, oral, single dose

Drug: Olanzapine 10 milligram

Olanzapine plus bromocriptine

EXPERIMENTAL

Olanzapine, 10mg, oral, single dose Bromocriptine, 5mg, oral, single dose

Drug: Olanzapine 10 milligram; Drug: Bromocriptine 5 milligram

Placebo

PLACEBO COMPARATOR

Placebo, oral, single dose

Drug: Placebo oral tablet

Interventions

Olanzapine 10 milligram DRUG

Oral olanzapine capsule

Olanzapine; Olanzapine plus bromocriptine

Bromocriptine 5 milligram DRUG

Oral bromocriptine capsule

Olanzapine plus bromocriptine

Placebo oral tablet DRUG

oral placebo capsules

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

RECRUITING

Study Officials

• Satya Dash, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Priska Stahel, PhD

CONTACT

416-581-7487; priska.stahel@uhn.ca

Satya Dash, MD

CONTACT

416-340-4800; satya.dash@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Single-blinded study with participant blinded to treatment
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: November 25, 2019
• First Posted: November 29, 2019
• Study Start: January 1, 2019
• Primary Completion: January 1, 2020
• Study Completion: June 1, 2020
• Last Updated: December 3, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)