Molecular Mechanisms of Antipsychotic-induced Insulin Resistance

Study Overview
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Brief Summary
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This study will investigate the molecular mechanisms of atypical-antipsychotic induced insulin resistance. This will be accomplished by administering olanzapine or placebo to healthy subjects for 7 days and analyzing genetic and protein changes in peripheral tissues known to play an important role in insulin resistance pathophysiology.

Official Title
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Molecular Mechanisms of Antipsychotic-induced Insulin Resistance in Healthy Volunteers

Conditions
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Adverse Effect of Other Antipsychotics and Neuroleptics, Insulin Resistance

Intervention / Treatment
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* Drug: olanzapine
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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We will include persons that meet the following criteria: 21-45 years old BMI 18.5-24.9kg/m2 No history of drug or alcohol dependence or abuse No current or past history of psychiatric or neurologic disease minimal exercise routine prior or during study (light walking allowed) Normal liver function tests minimal alcohol intake (<1 drink per day). The following persons will be excluded: Has 1st degree relative with diabetes (I or II) current or re-cent nicotine intake presence of organic/physical disease that could affect glucose currently taking prescription or over-the-counter medications that could affect glucose currently pregnant or lactating unwilling to take acceptable birth control method current or previous exposure to antipsychotics history of unstable weight personal or family history of cardiac arrhythmias or seizures current or past history of eating disorder(s) or restricted diet allergy to lidocaine or drug excipients history of difficulty with intravenous line placement history of fainting.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: olanzapine<br>Atypical antipsychotic | Drug: olanzapine<br>* atypical antipsychotic<br>* Other names: Zyprexa;|
| Placebo Comparator: placebo<br>Placebo comparator | Drug: placebo<br>* placebo control<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in DNA methylation | Change in peripheral tissue candidate gene methylation will be measured in the olanzapine intervention group compared to placebo | Baseline (day 1) to endpoint of intervention (day 7) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in protein levels | Change in peripheral tissue candidate protein levels will be measured in the olanzapine intervention group compared to placebo | Baseline (day 1) to endpoint of intervention (day 7) | 
| Change in protein activity | Change in peripheral tissue candidate protein phosphorylation will be measured in the olanzapine intervention group compared to placebo | Baseline (day 1) to endpoint of intervention (day 7) |