Adverse Effect of Other Antipsychotics and Neuroleptics, Insulin Resistance
Conditions
Brief summary
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.
Interventions
atypical antipsychotic
placebo control
Sponsors
Study design
Eligibility
Inclusion criteria
We will include persons that meet the following criteria: 1. 21-45 years old 2. BMI 18.5-24.9kg/m2 3. No history of drug or alcohol dependence or abuse 4. No current or past history of psychiatric or neurologic disease 5. minimal exercise routine prior or during study (light walking allowed) 6. Normal liver function tests 7. minimal alcohol intake (\<1 drink per day). The following persons will be excluded: 1. Has 1st degree relative with diabetes (I or II) 2. current or re-cent nicotine intake 3. presence of organic/physical disease that could affect glucose 4. currently taking prescription or over-the-counter medications that could affect glucose 5. currently pregnant or lactating 6. unwilling to take acceptable birth control method 7. current or previous exposure to antipsychotics 8. history of unstable weight 9. personal or family history of cardiac arrhythmias or seizures 10. current or past history of eating disorder(s) or restricted diet 11. allergy to lidocaine or drug excipients 12. history of difficulty with intravenous line placement 13. history of fainting.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in DNA methylation | Baseline (day 1) to endpoint of intervention (day 7) | Change in peripheral tissue candidate gene methylation will be measured in the olanzapine intervention group compared to placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in protein levels | Baseline (day 1) to endpoint of intervention (day 7) | Change in peripheral tissue candidate protein levels will be measured in the olanzapine intervention group compared to placebo |
| Change in protein activity | Baseline (day 1) to endpoint of intervention (day 7) | Change in peripheral tissue candidate protein phosphorylation will be measured in the olanzapine intervention group compared to placebo |
Countries
United States