Effect of Atypical Antipsychotic Drugs Olanzapine and Amisulpride on Glucose Metabolism

Central Institute of Mental Health, Mannheim

Status: Completed

Conditions: Diabetes; Schizophrenia; Insulin Resistance

Treatments: Drug: Amisulpride; Drug: Placebo; Drug: Olanzapine; Procedure: Glucose clamp technique

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01160991

DeuOlanAmi

Details and patient eligibility

About

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.

Full 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.

Enrollment: 10 patients

Sex: Male

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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10 participants in 3 patient groups, including a placebo group

Amisulpride

Active Comparator group

Description:

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

Treatment:

Procedure: Glucose clamp technique

Drug: Amisulpride

Olanzapine

Experimental group

Description:

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

Treatment:

Procedure: Glucose clamp technique

Drug: Olanzapine

Placebo

Placebo Comparator group

Description:

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

Treatment:

Procedure: Glucose clamp technique

Drug: Placebo