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

NCT00625170 | Completed

• 1 other identifier: P03.136
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Insulin Resistance; Dyslipidemia

Keywords

Antipsychotics; Olanzapine; Haloperidol; Insulin resistance; Dyslipidemia

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

1

ACTIVE COMPARATOR

Healthy men

Drug: olanzapine

2

ACTIVE COMPARATOR

Healthy men with a positive family anamneses of schizophrenia

Drug: olanzapine; Drug: Haloperidol

Interventions

olanzapine DRUG

olanzapine 10 mg/day for 8 days

Also known as: Zyprexa

1; 2

Haloperidol DRUG

haloperidol 3 mg/day for 8 days

2

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Leiden University Medical Center: lead
• Dutch Diabetes Research Foundation: collaborator

Study Sites (1)

Leiden University Medical Center

Leiden, 2300 RC, Netherlands

Location

MeSH Terms

Conditions

Insulin Resistance; Dyslipidemias

Interventions

Olanzapine; Haloperidol

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Butyrophenones; Ketones; Organic Chemicals

Study Officials

• Hanno Pijl, Phd MD

  Leiden University Medical Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 19, 2008
• First Posted: February 28, 2008
• Study Start: May 1, 2004
• Primary Completion: December 1, 2004
• Study Completion: December 1, 2004
• Last Updated: February 28, 2008

Record last verified: 2004-03

Locations

NL (1)