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

Sponsor

Leiden University Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT00625170

Collaborator

Dutch Diabetes Research Foundation (Other)

Enrollment

Location

Arms

Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Insulin Resistance Dyslipidemia	Drug: olanzapine Drug: Haloperidol	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

11 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Official Title:

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

Study Start Date :

May 1, 2004

Actual Primary Completion Date :

Dec 1, 2004

Actual Study Completion Date :

Dec 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Healthy men	Drug: olanzapine olanzapine 10 mg/day for 8 days Other Names: Zyprexa
Active Comparator: 2 Healthy men with a positive family anamneses of schizophrenia	Drug: olanzapine olanzapine 10 mg/day for 8 days Other Names: Zyprexa Drug: Haloperidol haloperidol 3 mg/day for 8 days

Arm

Intervention/Treatment

Active Comparator: 1

Healthy men

Drug: olanzapine

olanzapine 10 mg/day for 8 days

Other Names:

Zyprexa

Active Comparator: 2

Healthy men with a positive family anamneses of schizophrenia

Drug: olanzapine

olanzapine 10 mg/day for 8 days

Other Names:

Zyprexa

Drug: Haloperidol

haloperidol 3 mg/day for 8 days

Outcome Measures

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. [8 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 40 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

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)