Soluble Epoxide Hydrolase Inhibition and Insulin Resistance

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-05-17

Study Completion Date

2021-11-18

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Inhibiting GABA Transaminase to Relieve Obesity Induced Hyperinsulinemia and Insulin Resistance

NCT04062890

Hyperinsulinism Insulin Resistance Insulin Sensitivity +2 more

WITHDRAWN PHASE2

Resveratrol-Leucine Metabolite Synergy in Pre-diabetes

NCT01593605

Impaired Glucose Tolerance

COMPLETED NA

Early Phase Pre-Clinical and Initial Clinical Research on Epicatechin (Part 2)

NCT02656212

Pre-diabetes

COMPLETED PHASE1

Effect of Dietary Polyphenols on Insulin Sensitivity

NCT00668928

Insulin Resistance

COMPLETED PHASE1

Antioxidant Treatment of Type 2 Diabetes

NCT00609102

Type 2 Diabetes

COMPLETED EARLY_PHASE1

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders PreDiabetes Obesity

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Arm 1 and 2 are crossover arms

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Arms 1/2 are placebo controlled and blinded to investigator and participant

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Placebo then GSK2256294

Subjects will receive placebo oral capsule daily by mouth for 7 days, then seven week washout and then GSK2256294 daily by mouth for 7 days.

Group Type EXPERIMENTAL

GSK2256294

Intervention Type DRUG

Drug will be taken daily by mouth for 7 days.

Placebo oral capsule

Intervention Type DRUG

Placebo will be taken daily by mouth for 7 days.

GSK2256294 then Placebo

Subjects will receive GSK2256294 daily by mouth for 7 days, then seven week washout and then placebo oral capsule daily by mouth for 7 days.

Group Type EXPERIMENTAL

GSK2256294

Intervention Type DRUG

Drug will be taken daily by mouth for 7 days.

Placebo oral capsule

Intervention Type DRUG

Placebo will be taken daily by mouth for 7 days.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

GSK2256294

Drug will be taken daily by mouth for 7 days.

Intervention Type DRUG

Placebo oral capsule

Placebo will be taken daily by mouth for 7 days.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

GSK2256294 10mg oral capsule Placebo

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Men and women,
2. Age 21 to 50 years, and
3. Pre-diabetes as defined by

1. Fasting plasma glucose 100-125 mg/dL, or
2. Two-hour plasma glucose 140-199 mg/dL, or
3. HbA1c 5.7-6.4%
4. BMI ≥ 30 kg/m2, inclusive
5. For female subjects, the following conditions must be met:

1. Postmenopausal status for at least one year, or
2. Status-post surgical sterilization, or
3. If of childbearing potential, utilization of adequate birth control and willingness to undergo serum β-hcg testing prior to drug treatment and on every study day.

Exclusion Criteria

1. Diabetes type 1 or type 2, as defined by a fasting plasma glucose of 126 mg/dL or greater, a two-hour plasma glucose of 200 mg/dL or greater, a HbA1c \>6.4%, or the use of anti-diabetic medication
2. Subjects who have participated in a weight-reduction program during the last six month or whose weight has increased or decreased more than two kg over the preceding six months
3. Resistant hypertension, defined as hypertension requiring the administration of more than three anti-hypertensive agents including a diuretic to achieve control
4. Use of spironolactone
5. Pregnancy or breast-feeding
6. Any history of smoking
7. Any history of cancer including skin cancer, any history of a precancerous lesion, abnormal PSA, or lack of screening adherent to American Cancer Society Guidelines for the Early Detection of Cancer
8. Cardiovascular disease such as myocardial infarction within six months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (left ventricular hypertrophy acceptable), deep-vein thrombosis, pulmonary embolism, second- or third-degree heart block, mitral valve stenosis, aortic stenosis, or hypertrophic cardiomyopathy
9. Abnormal corrected QT interval on screening ECG (QTc).
10. Treatment with anticoagulants
11. History of serious neurologic disease such as cerebral hemorrhage, stroke, or transient ischemic attack
12. History or presence of immunological or hematological disorders
13. Diagnosis of asthma requiring regular inhaler use
14. Clinically significant gastrointestinal impairment that could interfere with drug absorption
15. Impaired hepatic function (aspartate amino transaminase \[AST\] and/or alanine amino transaminase \[ALT\] \>3.0 x upper limit of normal range)
16. History of gastrointestinal bleed
17. Estimated glomerular filtration rate (eGFR)\<60 mL/min/1.73 m2 or with an albumin-to-creatinine ratio (UACR) \>300µg/mg, where eGFR is determined by the four-variable Modification of Diet in Renal Disease (MDRD) equation, where serum creatinine is expressed in mg/dL and age in years: eGFR (mL/min/1.73m2)=186 • Scr-1.154 • age-0.203 • (1.212 if black) • (0.742 if female)
18. Hematocrit \<35%
19. Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult
20. Treatment with chronic systemic glucocorticoid therapy
21. Treatment with lithium salts
22. History of alcohol or drug abuse
23. Treatment with any investigational drug in the month preceding the study
24. Mental conditions rendering a subject unable to understand the nature, scope, and possible consequences of the study
25. Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study

Minimum Eligible Age

21 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes