Antipsychotics and Gene Expression in Soft Tissues

Study Overview
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Brief Summary
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Schizophrenia is a severe chronic and disabling mental disorder and is associated with a significant reduction in life expectancy. Atypical antipsychotic treatment compliance may be jeopardized because of drug induced weight gain and abnormalities in carbohydrate and lipid metabolism. Aim: to gain data on drug related effects on gene expression and regulation with special regard to glucose metabolism.

Official Title
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Effect of Atypical Antipsychotics on Gene Expression in Soft Tissues of Healthy Subjects - A Placebo Controlled Randomised Pilot Study

Conditions
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Schizophrenia, Diabetes

Intervention / Treatment
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* Drug: olanzapine
* Drug: ziprasidone
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male. Healthy, defined as absence of relevant diseases. Caucasian. Aged 18-45 years. Body-Mass-Index (BMI): 18-25 kg/m2. Signed informed consent. No signs of impaired glucose tolerance as evaluated by Oral Glucose Tolerance Test (OGTT) before study inclusion during screening, normal total cholesterol, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), triglycerides, normal function of the thyroid. No personal or family history (parents and siblings) of diabetes or other metabolic and relevant diseases as defined by the investigator. No indication for psychiatric diseases assessed by structured clinical interview (Mini-International Neuropsychiatric Interview (MINI)). Exclusion Criteria: Personal or family history (parents and siblings) of diabetes or other metabolic diseases, relevant diseases as defined by the investigator. History of hypertension, blood pressure > 140/90 at screening, cardiovascular disease. Body mass index out of the range of <18 and >25 kg/m. Human immunodeficiency virus (HIV) or Hepatitis B/C positive virology. Allergy or hypersensitivity against olanzapine/ziprasidone or another excipient. Contraindications against the use of the drug according to the Summary of Product Characteristics (SmPC). Any drug intake 2 weeks prior to first study day. History of excessive bleeding tendency/hemophilia. Presence of relevant illness within the last 3 weeks. Currently enrolled into an other clinical study with Investigational Medicinal Products (IMPs). Last study participation less than 4 weeks. Suspected non-compliance with study instructions and life-style requirements. History of alcohol or drug abuse. Blood/Plasma donation within 4 weeks prior to study day. Previous exposure to antipsychotic drugs. Nicotine consumption at time of enrolment (at least 3 months of non-smoking required).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: olanzapine<br>olanzapine | Drug: olanzapine<br>* olanzapine 10mg od + placebo od<br>Drug: ziprasidone<br>* ziprasidone 40mg td<br>|
| Active Comparator: ziprasidone<br>ziprasidone | Drug: olanzapine<br>* olanzapine 10mg od + placebo od<br>Drug: ziprasidone<br>* ziprasidone 40mg td<br>|
| Placebo Comparator: Sugar pill<br>Sugar pill | Drug: placebo<br>* placebo td<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| gene expression profiling | To characterize and compare the gene expression profiles in human subcutaneous adipose and muscle tissue prior and after single dose of olanzapine, ziprasidone and placebo. | 10 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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healthy volunteers, antipsychotics, gene expression