Status:
COMPLETED
Soluble Epoxide Hydrolase Inhibition and Insulin Resistance
Lead Sponsor:
Vanderbilt University Medical Center
Collaborating Sponsors:
National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Conditions:
Diabetes Mellitus
Endocrine System Diseases
Eligibility:
All Genders
21-50 years
Phase:
PHASE2
Brief 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 isotop...
Eligibility Criteria
Inclusion
- Men and women,
- Age 21 to 50 years, and
- Pre-diabetes as defined by
- Fasting plasma glucose 100-125 mg/dL, or
- Two-hour plasma glucose 140-199 mg/dL, or
- HbA1c 5.7-6.4%
- BMI ≥ 30 kg/m2, inclusive
- For female subjects, the following conditions must be met:
- Postmenopausal status for at least one year, or
- Status-post surgical sterilization, or
- 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
- 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
- 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
- Resistant hypertension, defined as hypertension requiring the administration of more than three anti-hypertensive agents including a diuretic to achieve control
- Use of spironolactone
- Pregnancy or breast-feeding
- Any history of smoking
- 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
- 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
- Abnormal corrected QT interval on screening ECG (QTc).
- Treatment with anticoagulants
- History of serious neurologic disease such as cerebral hemorrhage, stroke, or transient ischemic attack
- History or presence of immunological or hematological disorders
- Diagnosis of asthma requiring regular inhaler use
- Clinically significant gastrointestinal impairment that could interfere with drug absorption
- Impaired hepatic function (aspartate amino transaminase \[AST\] and/or alanine amino transaminase \[ALT\] \>3.0 x upper limit of normal range)
- History of gastrointestinal bleed
- 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)
- Hematocrit \<35%
- 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
- Treatment with chronic systemic glucocorticoid therapy
- Treatment with lithium salts
- History of alcohol or drug abuse
- Treatment with any investigational drug in the month preceding the study
- Mental conditions rendering a subject unable to understand the nature, scope, and possible consequences of the study
- Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study
Key Trial Info
Start Date :
May 17 2018
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
November 18 2021
Estimated Enrollment :
16 Patients enrolled
Trial Details
Trial ID
NCT03486223
Start Date
May 17 2018
End Date
November 18 2021
Last Update
March 23 2023
Active Locations (1)
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1
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232