Effect of Atypical Antipsychotic Drugs Olanzapine and Amisulpride on Glucose Metabolism

NCT ID: NCT01160991

Last Updated: 2010-08-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-05-31
• Study Completion Date: 2006-10-31

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.

Conditions

Schizophrenia; Diabetes; Insulin Resistance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Amisulpride

Single dose of amisulpride 200 mg p.o. given at 8:00 a.m.

Group Type: ACTIVE_COMPARATOR

Glucose clamp technique

Intervention Type: PROCEDURE

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

Amisulpride

Intervention Type: DRUG

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.

Group Type: EXPERIMENTAL

Glucose clamp technique

Intervention Type: PROCEDURE

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

Olanzapine

Intervention Type: DRUG

Single dose of olanzapine 10 mg p.o. given at 8:00 a.m.

Placebo

Placebo capsules are given at 8:00 a.m. Procedures are performed as described above.

Group Type: PLACEBO_COMPARATOR

Glucose clamp technique

Intervention Type: PROCEDURE

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

Placebo

Intervention Type: DRUG

Placebo capsules are given at 8:00 a.m.

Interventions

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

Intervention Type: PROCEDURE

Amisulpride

Single dose of amisulpride 200 mg p.o. given at 8:00 a.m.

Intervention Type: DRUG

Olanzapine

Single dose of olanzapine 10 mg p.o. given at 8:00 a.m.

Intervention Type: DRUG

Placebo

Placebo capsules are given at 8:00 a.m.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

Central Institute of Mental Health, Mannheim

OTHER

Sponsor Role: lead

Responsible Party

Central Institute of Mental Health

Principal Investigators

Daniel Kopf, M.D.

Role: PRINCIPAL_INVESTIGATOR

Central Institute of Mental Health, Mannheim

Locations

Central Institute of Mental Health

Mannheim, , Germany

Countries

Germany

Other Identifiers

DeuOlanAmi

Identifier Type: -

Identifier Source: org_study_id