Molecular Mechanisms of Antipsychotic-induced Insulin Resistance

Molecular Mechanisms of Antipsychotic-induced Insulin Resistance in Healthy Volunteers

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.

Study Overview

• Status: Completed
• Conditions: Insulin Resistance; Adverse Effect of Other Antipsychotics and Neuroleptics
• Intervention / Treatment: Drug: placebo; Drug: olanzapine

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Wayne State University Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; Placebo comparator	Drug: placebo; placebo control
Experimental: olanzapine; Atypical antipsychotic	Drug: olanzapine; atypical antipsychotic; Other Names: Zyprexa

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Wayne State University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2017
• Primary Completion (Actual): October 1, 2023
• Study Completion (Actual): October 1, 2023

Study Registration Dates

• First Submitted: March 5, 2016
• First Submitted That Met QC Criteria: March 9, 2016
• First Posted (Estimated): March 15, 2016

Study Record Updates

• Last Update Posted (Actual): October 31, 2023
• Last Update Submitted That Met QC Criteria: October 27, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Selective Serotonin Reuptake Inhibitors; Olanzapine
• Other Study ID Numbers: MMAAPWSU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No