Soluble Epoxide Hydrolase Inhibition and Insulin Resistance
Last updated on July 2021Recruitment
- Recruitment Status
- Recruiting
- Estimated Enrollment
- 34
Summary
- Conditions
- Diabetes Mellitus
- Endocrine System Diseases
- Glucose Metabolism Disorders
- Obesity
- Prediabetes
- Type
- Interventional
- Phase
- Phase 2
- Design
- Allocation: RandomizedIntervention Model: Crossover AssignmentIntervention Model Description: Arm 1 and 2 are crossover arms and we have added arm 3 as a single arm.Masking: Double (Participant, Investigator)Primary Purpose: Prevention
Participation Requirements
- Age
- Between 21 years and 50 years
- Gender
- Both males and females
Description
AIM 1: We will test the hypothesis that the loss-of-function variant (287Gln) in EPHX2 is associated with insulin sensitivity using the gold-standard, hyperinsulinemic-euglycemic clamps, with stable isotope dilution to assess hepatic gluconeogenesis. We will assess the relationship between genotype ...
AIM 1: We will test the hypothesis that the loss-of-function variant (287Gln) in EPHX2 is associated with insulin sensitivity using the gold-standard, hyperinsulinemic-euglycemic clamps, with stable isotope dilution to assess hepatic gluconeogenesis. We will assess the relationship between genotype and 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. 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. AIM 2: 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.
Tracking Information
- NCT #
- NCT03486223
- Collaborators
- National Institutes of Health (NIH)
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Investigators
- Principal Investigator: James M Luther, MD Vanderbilt University Medical Center Principal Investigator: Nancy J Brown, MD Vanderbilt University Medical Center
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