Effect of Short Term Atypical Antipsychotic Administration Compared to Placebo on Hepatic Insulin Extraction

• Status: Completed
• Trial end date: 2014-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Within the past 20 years, there has been a striking increase in the incidence of obesity 1;2, type 2 diabetes mellitus (T2DM) 3-5, and cardiovascular diseases (CVD) in the schizophrenic population 6-8 . Large NIH-funded trials indicate that the prevalence of metabolic syndrome is twice to three times greater in schizophrenic patients on a specific class of drug termed the "atypical antipsychotics" (AAPs), of which olanzapine is an example, as compared to matched controls 8. Identification of the pathophysiological mechanisms contributing to metabolic disease in schizophrenic patients on AAPs has been hampered by the inability to differentiate underlying disease from treatment-emergent complications. In addition, despite falling within the same drug class, different AAPs exhibit differential associations with metabolic disease. Olanzapine is one of the AAPs associated with the greatest weight gain and degree of metabolic impairments.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Michael Rickels
• Collaborator: University of Pennsylvania
• Treatments: Antipsychotic Agents; Olanzapine

Criteria

Inclusion Criteria:

1. Men and women ages 18-40

2. BMI 19-24.5kg/m2

3. Systolic BP <130mm Hg

4. Diastolic BP <85mm Hg

5. Subjects capable of giving informed consent, with no past or present psychiatric history

6. Only women on oral contraceptives with constant dosing regimens or Depo-Provera for >3 months, to ensure uniform hormonal delivery throughout the study duration

7. No medications except as above noted

8. Weight stable

9. Minimal exercise regime that includes walking, running or biking

Exclusion Criteria:

1. History of heart disease, colitis, autonomic neuropathy, hepatic or renal disease

2. DSM-IV diagnosis of past or present psychiatric history, including clinically significant depression

3. Drug/Alcohol dependence, homelessness, or inability to give informed consent

4. History of asthma, congenital obstructive bladder, peptic ulcer, vasomotor instability, epilepsy, Parkinsonism, elevated thyroid hormone levels

5. Diagnosis of diabetes

6. BMI>25 kg/m2

7. Prescription medication (excluding the contraceptive methods described above)

8. Hemoglobin <11

9. Abnormal laboratory tests which are clinically significant per the investigator

10. Females pregnant or lactating

11. Females: not taking hormonal contraceptives; taking hormonal contraceptives of varying dosage throughout the month

12. Currently on a weight loss diet

13. Moderate to significant exercise regime that includes swimming, weight lifting or other form of exercise not reproducible within CTRC.