Effect of Atypical Antipsychotic Drugs Olanzapine and Amisulpride on Glucose Metabolism

Not Applicable

Completed

• Conditions: Diabetes; Schizophrenia; Insulin Resistance
• Interventions: Procedure: Glucose clamp technique; Drug: Placebo; Drug: Amisulpride; Drug: Olanzapine

• Registration Number: NCT01160991
• Lead Sponsor: Central Institute of Mental Health, Mannheim

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 2004-05
• Primary Completion: 2006-10
• Study Completion: 2006-10
• Study First Submitted: 2010-07-09
• Study First Submitted QC: 2010-07-12
• Study First Posted: 2010-07-13
• Status Verified: 2010-08
• Last Update Submitted: 2010-08-02
• Last Update Posted: 2010-08-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 10

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

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Amisulpride	Glucose clamp technique	Single dose of amisulpride 200 mg p.o. given at 8:00 a.m.
Placebo	Glucose clamp technique	Placebo capsules are given at 8:00 a.m. Procedures are performed as described above.
Olanzapine	Glucose clamp technique	Single dose of olanzapine 10 mg p.o. given at 8:00 a.m.
Placebo	Placebo	Placebo capsules are given at 8:00 a.m. Procedures are performed as described above.
Amisulpride	Amisulpride	Single dose of amisulpride 200 mg p.o. given at 8:00 a.m.
Olanzapine	Olanzapine	Single dose of olanzapine 10 mg p.o. given at 8:00 a.m.

Primary Outcome Measures

Name	Time	Method
insulin sensitivity	90 thru 120 min after application of study drug	m-value during euglycemic glucose clamp (glucose infusion rate divided by time and body weight)

Secondary Outcome Measures

Name	Time	Method
pancratic c-peptide secretion	120 thru 180 minutes after administration of study drug	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

Trial Locations

Locations (1)

Central Institute of Mental Health; 🇩🇪 Mannheim, Germany