Effect of Atypical Antipsychotic Drugs Olanzapine and Amisulpride on Glucose Metabolism

This study has been completed.
Sponsor:
Collaborator:
Sanofi
Information provided by:
Central Institute of Mental Health, Mannheim
ClinicalTrials.gov Identifier:
NCT01160991
First received: July 9, 2010
Last updated: August 2, 2010
Last verified: August 2010
  Purpose

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 Intervention
Schizophrenia
Diabetes
Insulin Resistance
Procedure: Glucose clamp technique
Drug: Amisulpride
Drug: Olanzapine
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, 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:

Resource links provided by NLM:


Further study details as provided by Central Institute of Mental Health, Mannheim:

Primary Outcome Measures:
  • insulin sensitivity [ Time Frame: 90 thru 120 min after application of study drug ] [ Designated as safety issue: Yes ]
    m-value during euglycemic glucose clamp (glucose infusion rate divided by time and body weight)


Secondary Outcome Measures:
  • pancratic c-peptide secretion [ Time Frame: 120 thru 180 minutes after administration of study drug ] [ Designated as safety issue: Yes ]
    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


Enrollment: 10
Study Start Date: May 2004
Study Completion Date: October 2006
Primary Completion Date: October 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01160991

Locations
Germany
Central Institute of Mental Health
Mannheim, Germany, 68159
Sponsors and Collaborators
Central Institute of Mental Health, Mannheim
Sanofi
Investigators
Principal Investigator: Daniel Kopf, M.D. Central Institute of Mental Health, Mannheim
  More Information

No publications provided

Responsible Party: Michael Deuschle, Central Institute of Mental Health
ClinicalTrials.gov Identifier: NCT01160991     History of Changes
Other Study ID Numbers: DeuOlanAmi
Study First Received: July 9, 2010
Last Updated: August 2, 2010
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Central Institute of Mental Health, Mannheim:
schizophrenia
olanzapine
atypical antipsychotic drugs
amisulpride
diabetes
insulin resistance
insulin secretion
glucose
euglycemic hyperinsulinemic clamp
hyperglycemic clamp

Additional relevant MeSH terms:
Insulin Resistance
Schizophrenia
Glucose Metabolism Disorders
Hyperinsulinism
Mental Disorders
Metabolic Diseases
Schizophrenia and Disorders with Psychotic Features
Antipsychotic Agents
Insulin
Olanzapine
Sulpiride
Sultopride
Antidepressive Agents
Antidepressive Agents, Second-Generation
Antiemetics
Autonomic Agents
Central Nervous System Agents
Central Nervous System Depressants
Dopamine Agents
Dopamine Antagonists
Gastrointestinal Agents
Hypoglycemic Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents

ClinicalTrials.gov processed this record on October 22, 2014