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

Insulin Resistance Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00625170
• Other study ID #: P03.136
• Status: Completed
• Phase: N/A
• First received: February 19, 2008
• Last updated: February 19, 2008
• Start date: May 2004
• Est. completion date: December 2004

Study information

• Verified date: March 2004
• Source: Leiden University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: December 2004
• Est. primary completion date: December 2004
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 40 Years

Eligibility

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)

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject)

Related Conditions & MeSH terms

• Dyslipidemia
• Dyslipidemias
• Insulin Resistance

Intervention

Drug:
• olanzapine
olanzapine 10 mg/day for 8 days
• Haloperidol
haloperidol 3 mg/day for 8 days

Locations

Country	Name	City	State
Netherlands	Leiden University Medical Center	Leiden

Sponsors (2)

Lead Sponsor	Collaborator
Leiden University Medical Center	Dutch Diabetes Research Foundation

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the effect of subchronic olanzapine and haloperidol treatment on HGO, whole body peripheral glucose disposal, fatty acid flux and fuel oxidation.		8 days	No