Effect of Atypical Antipsychotic Drugs Olanzapine and Amisulpride on Glucose Metabolism

Schizophrenia Clinical Trial

Official title:

Effects of the Serotonin 2A Receptor on Insulin Sensitivity and Secretion: a Double-blind Controlled Comparison of Olanzapine vs. Amisulpride:

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01160991
• Other study ID #: DeuOlanAmi
• Status: Completed
• Phase: N/A
• First received: July 9, 2010
• Last updated: August 2, 2010
• Start date: May 2004
• Est. completion date: October 2006

Study information

• Verified date: August 2010
• Source: Central Institute of Mental Health, Mannheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

Patients suffering from schizophrenia have a high risk to become obese and develop diabetes. Risk of obesity is particularly high with some newer schizophrenia drugs, such as clozapine or olanzapine. These drugs are called atypical drugs and exert their action in part by occupying receptors for serotonin, particularly the 5HT2A receptor subtype. This receptor may also interfere with glucose metabolism and insulin action. The purpose of this study is to compare an atypical antipsychotic drugs, olanzapine, which acts by occupying the 5HT2A receptor, to another antipsychotic drug, amisulpride, which mainly acts through the dopamine pathway. Healthy volunteers are recruited and asked to take a single dose of each drug and of placebo on separate days. Then, a combined glucose clamp study will be performed in order to test the effects of these drugs on insulin sensitivity and insulin secretion.

Description:

10 male healthy volunteers are recruited. After informed consent, they are admitted to the study ward at 10:00 p.m. prior to the study day and kept fasting until the next morning. At 8:00 a.m. they receive their study medication (olanzapine, amisulpride or placebo). Subsequently, measurements of insulin sensitivity and insulin secretion are performed by euglycemic hyperinsulinemic clamp technique followed by hyperglycemic clamp.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: October 2006
• Est. primary completion date: October 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• healthy male volunteers

• written informed consent

Exclusion Criteria:

• BMI > 30 kg/m²

• Diabetes mellitus

• Hypertension

• Treatment with drugs interfering with lipid or glucose metabolism (e.g. statins, oral antidiabetic drugs, glucocorticoids)

• History of seizures

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes
• Insulin Resistance
• Schizophrenia

Intervention

Procedure:
• Glucose clamp technique
euglycemic hyperinsulinemic clamp with target blood glucose of 90 mg/dl (5 mmol/l), followed by hyperglycemic clamp, target blood glucose of 180 mg/dl (10 mmol/l) for measurement of insulin sensitivity and insulin secretion

Drug:
• Amisulpride
Single dose of amisulpride 200 mg p.o. given at 8:00 a.m.
• Olanzapine
Single dose of olanzapine 10 mg p.o. given at 8:00 a.m.
• Placebo
Placebo capsules are given at 8:00 a.m.

Locations

Country	Name	City	State
Germany	Central Institute of Mental Health	Mannheim

Sponsors (2)

Lead Sponsor	Collaborator
Central Institute of Mental Health, Mannheim	Sanofi

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	insulin sensitivity	m-value during euglycemic glucose clamp (glucose infusion rate divided by time and body weight)	90 thru 120 min after application of study drug	Yes
Secondary	pancratic c-peptide secretion	C-peptide measured 4 times during hyperglycemic clamp period at time 0 min (prior to glucose bolus), 5 min, 10 min and 60 min after glucose bolus	120 thru 180 minutes after administration of study drug	Yes