NCT03486223

Soluble Epoxide Hydrolase Inhibition and Insulin Resistance

Effect of Inhibition Soluble Epoxide Hydrolase on Insulin Sensitivity in Humans

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 16 (actual)
• Sponsor: Vanderbilt University Medical Center · Academic / Other
• Sex: All
• Age: 21 Years – 50 Years
• Healthy volunteers: Accepted

Summary

The purpose of this study is to test how soluble epoxide hydrolase (sEH) inhibition with GSK2256294 affects tissue sEH activity and insulin sensitivity.

Detailed description

We will test the hypothesis that soluble epoxide hydrolase (sEH) inhibition with GSK2256294 improves insulin sensitivity using the gold-standard, hyperinsulinemic-euglycemic clamps, with stable isotope dilution to assess hepatic gluconeogenesis. We will assess insulin-stimulated vasodilation in the forearm using plethysmography and in the renal vasculature using para-aminohippurate (PAH, IND#133828) clearance. We will obtain adipose and muscle tissue before and after clamp to assess insulin signaling in these tissues. Subjects are randomized to treatment with the sEH inhibitor GSK2256294 (10mg/day) or matching placebo for one week. On the seventh day of drug treatment, subjects will report to the CRC in the morning after an overnight fast to undergo a hyperinsulinemic-euglycemic clamp with adipose tissue biopsies. During the Hyperinsulinemic-euglycemic clamp, insulin will be infused for 2 hours at low dose (20 mU/m2/min) and 2 hours at high dose (80 mU/m2/min) to assess insulin sensitivity. The Glucose Infusion Rate (GIR) will be adjusted to maintain glucose near 95 mg/dL. The average GIR during the final 30 minutes of the high dose period will be used as the measure of insulin sensitivity. After completion of the study day, subjects will undergo a seven-week washout from study drug and then receive the opposite drug for one week. On the seventh day of treatment they will report to the CRC after an overnight fast and repeat the study day protocol.

Conditions

• Diabetes Mellitus
• Endocrine System Diseases
• Glucose Metabolism Disorders
• PreDiabetes
• Obesity

Interventions

Type	Name	Description
DRUG	GSK2256294	Drug will be taken daily by mouth for 7 days.
DRUG	Placebo oral capsule	Placebo will be taken daily by mouth for 7 days.

Timeline

• Start date: 2018-05-17
• Primary completion: 2021-11-18
• Completion: 2021-11-18
• First posted: 2018-04-03
• Last updated: 2023-03-23
• Results posted: 2023-03-23

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study