Metabolic Effects of Subchronic Dopamine D2 Receptor Blockade by Antipsychotic Drugs in Healthy Humans

This study has been completed.
Sponsor:
Collaborator:
Dutch Diabetes Research Foundation
Information provided by:
Leiden University Medical Center
ClinicalTrials.gov Identifier:
NCT00625170
First received: February 19, 2008
Last updated: NA
Last verified: March 2004
History: No changes posted
  Purpose

We hypothesized that short-term treatment with AP drugs induces insulin resistance through a mechanistic route that is independent of weight gain and that atypical drugs exert stronger effects than typical compounds in this respect. We therefore treated healthy non-obese men with olanzapine (atypical AP) or haloperidol (typical AP) for 8 days, and studied the impact of these interventions on glucose and lipid metabolism by hyperinsulinemic euglycemic clamp, isotope dilution technology and indirect calorimetry.


Condition Intervention
Insulin Resistance
Dyslipidemia
Drug: olanzapine
Drug: Haloperidol

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Official Title: Metabolic Effects of Subchronic Dopamine D2 Receptor Blockade by Antipsychotic Drugs in Healthy Humans

Resource links provided by NLM:


Further study details as provided by Leiden University Medical Center:

Primary Outcome Measures:
  • To determine the effect of subchronic olanzapine and haloperidol treatment on HGO, whole body peripheral glucose disposal, fatty acid flux and fuel oxidation. [ Time Frame: 8 days ] [ Designated as safety issue: No ]

Enrollment: 11
Study Start Date: May 2004
Study Completion Date: December 2004
Primary Completion Date: December 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Healthy men
Drug: olanzapine
olanzapine 10 mg/day for 8 days
Other Name: Zyprexa
Active Comparator: 2
Healthy men with a positive family anamneses of schizophrenia
Drug: olanzapine
olanzapine 10 mg/day for 8 days
Other Name: Zyprexa
Drug: Haloperidol
haloperidol 3 mg/day for 8 days

  Eligibility

Ages Eligible for Study:   20 Years to 40 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy men, with and without a positive family history of schizophrenia.
  • 20 kg/m2 < BMI < 26 kg/m2
  • Age 20-40 years
  • Fasting plasma glucose < 6 mmo/L

Exclusion Criteria:

  • FPG > 6 mmol/L
  • BMI > 26 kg/m2
  • Psychiatric disorders and/or use of antipsychotic or antidepressants drugs at present or in the past.
  • Any significant chronic disease
  • Renal, hepatic or endocrine disease
  • Use of medication known to influence lipolysis and/or glucose metabolism
  • Total cholesterol > 7mmol/L and/or triglycerides > 2 mmol/L
  • Recent weight changes or attempts to loose weight (> 3 kg weight gain or loss, within the last 3 months)
  • Difficulties to insert an intravenous catheter
  • Smoking (current)
  • Severe claustrophobia (ventilated hood)
  • Recent blood donation (within the last 2 months)
  • Recent participation in other research projects (within the last 3 months), participation in 2 or more projects in one year
  • Extensive sporting activities (more than 10 hours of exercise per week)
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00625170

Locations
Netherlands
Leiden University Medical Center
Leiden, Netherlands, 2300 RC
Sponsors and Collaborators
Leiden University Medical Center
Dutch Diabetes Research Foundation
Investigators
Study Chair: Hanno Pijl, Phd MD Leiden University Medical Center
  More Information

No publications provided

Responsible Party: Prof. Hanno Pijl, LUMC
ClinicalTrials.gov Identifier: NCT00625170     History of Changes
Other Study ID Numbers: P03.136
Study First Received: February 19, 2008
Last Updated: February 19, 2008
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Leiden University Medical Center:
Antipsychotics
Olanzapine
Haloperidol
Insulin resistance
Dyslipidemia

Additional relevant MeSH terms:
Insulin Resistance
Dyslipidemias
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Lipid Metabolism Disorders
Dopamine
Haloperidol
Olanzapine
Haloperidol decanoate
Antipsychotic Agents
Cardiotonic Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents
Antiemetics
Central Nervous System Agents
Gastrointestinal Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists

ClinicalTrials.gov processed this record on July 24, 2014