Effect of Atypical Antipsychotic Drugs Olanzapine and Amisulpride on Glucose Metabolism

Sponsor

Central Institute of Mental Health, Mannheim (Other)

Overall Status

Completed

CT.gov ID

NCT01160991

Collaborator

Sanofi (Industry)

Enrollment

Location

Arms

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia Diabetes Insulin Resistance	Procedure: Glucose clamp technique Drug: Amisulpride Drug: Olanzapine Drug: Placebo	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

10 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Basic Science

Official Title:

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

Study Start Date :

May 1, 2004

Actual Primary Completion Date :

Oct 1, 2006

Actual Study Completion Date :

Oct 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Amisulpride Single dose of amisulpride 200 mg p.o. given at 8:00 a.m.	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.
Experimental: Olanzapine Single dose of olanzapine 10 mg p.o. given at 8:00 a.m.	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: Olanzapine Single dose of olanzapine 10 mg p.o. given at 8:00 a.m.
Placebo Comparator: Placebo Placebo capsules are given at 8:00 a.m. Procedures are performed as described above.	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: Placebo Placebo capsules are given at 8:00 a.m.

Arm

Intervention/Treatment

Active Comparator: Amisulpride

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

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.

Experimental: Olanzapine

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

Procedure: Glucose clamp technique

Drug: Olanzapine

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

Placebo Comparator: Placebo

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

Procedure: Glucose clamp technique

Drug: Placebo

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

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

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