Molecular Mechanisms of Antipsychotic-induced Insulin Resistance

NCT02708394 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: MMAAPWSU
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Adverse Effect of Other Antipsychotics and Neuroleptics; Insulin Resistance

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Change in protein levels

  Baseline (day 1) to endpoint of intervention (day 7)

• Change in protein activity

  Baseline (day 1) to endpoint of intervention (day 7)

Study Arms (2)

olanzapine

EXPERIMENTAL

Atypical antipsychotic

Drug: olanzapine

placebo

PLACEBO COMPARATOR

Placebo comparator

Drug: placebo

Interventions

olanzapine DRUG

atypical antipsychotic

Also known as: Zyprexa

olanzapine

placebo DRUG

placebo control

placebo

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Wayne State University: lead

Study Sites (1)

Wayne State University Clinical Research Center

Detroit, Michigan, 48202, United States

Location

MeSH Terms

Conditions

Insulin Resistance

Interventions

Olanzapine

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: March 5, 2016
• First Posted: March 15, 2016
• Study Start: February 1, 2017
• Primary Completion: October 1, 2023
• Study Completion: October 1, 2023
• Last Updated: October 31, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)