Diabetes, Insulin Resistance, Schizophrenia
Conditions
Keywords
schizophrenia, olanzapine, atypical antipsychotic drugs, amisulpride, diabetes, insulin resistance, insulin secretion, glucose, euglycemic hyperinsulinemic clamp, hyperglycemic clamp
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.
Interventions
PROCEDUREGlucose 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
DRUGAmisulpride
Single dose of amisulpride 200 mg p.o. given at 8:00 a.m.
DRUGOlanzapine
Single dose of olanzapine 10 mg p.o. given at 8:00 a.m.
DRUGPlacebo
Placebo capsules are given at 8:00 a.m.
Sponsors
Sanofi
Central Institute of Mental Health, Mannheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Germany
Outcome results
None listed