Effects of the Serotonin 2A Receptor on Insulin Sensitivity and Secretion: a Double-blind Controlled Comparison of Olanzapine vs. Amisulpride:
Overview
- Phase
- Not Applicable
- Intervention
- Glucose clamp technique
- Conditions
- Schizophrenia
- Sponsor
- Central Institute of Mental Health, Mannheim
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- insulin sensitivity
- Status
- Completed
- Last Updated
- 15 years ago
Overview
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.
Investigators
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
Arms & Interventions
Amisulpride
Single dose of amisulpride 200 mg p.o. given at 8:00 a.m.
Intervention: Glucose clamp technique
Amisulpride
Single dose of amisulpride 200 mg p.o. given at 8:00 a.m.
Intervention: Amisulpride
Olanzapine
Single dose of olanzapine 10 mg p.o. given at 8:00 a.m.
Intervention: Glucose clamp technique
Olanzapine
Single dose of olanzapine 10 mg p.o. given at 8:00 a.m.
Intervention: Olanzapine
Placebo
Placebo capsules are given at 8:00 a.m. Procedures are performed as described above.
Intervention: Glucose clamp technique
Placebo
Placebo capsules are given at 8:00 a.m. Procedures are performed as described above.
Intervention: Placebo
Outcomes
Primary Outcomes
insulin sensitivity
Time Frame: 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 Outcomes
- pancratic c-peptide secretion(120 thru 180 minutes after administration of study drug)