Early Phase Pre-Clinical and Initial Clinical Research on Epicatechin

Phase 1

Completed

Brief Summary: Early Phase Pre-Clinical and Initial Clinical Research on (+)- Epicatechin.

Detailed Description: This project is a double-blinded randomized Phase I study that will include dose-ranging one day PK and pharmacodynamic (PD) studies. Subjects will include healthy individuals and subjects who meet the American Diabetes Association (ADA) criteria for pre-diabetes, including IFG.

Recruitment & Eligibility

Inclusion Criteria

Healthy or pre-diabetic based on medical history
Male or female
Must be 21 to 75 years of age (inclusive)
Able to give informed consent to the procedures
If female, must be either postmenopausal or test negative for pregnancy at screening and on the day of the procedure. Women on estrogen therapy will be included.
If of childbearing potential, must practice and be willing to continue to practice appropriate birth control during the entire duration of the study
Medication use stable for 4 weeks
Body Mass Index (BMI) > 27 kg/m^2
Definition of pre-diabetes: impaired fasting glucose (IFG, fasting glucose = 100-125 mg/dL) and elevated HbA1c (5.7-6.4%), each in the absence of other risk factors for diabetes

Exclusion Criteria

Type 2 diabetes
Pregnancy
Younger than 21 or older than 75 years of age
Clinically significant abnormalities in liver or kidney function (>3x ULN), determined in the last 6 months by a certified clinical laboratory
Recent MI or stroke (within 6 months of screening)
Blood pressure (BP) >160 mmHg Systolic and >100 mmHg Diastolic
Medications - thiazolidinediones, any steroids, anti-depressants, weight loss drugs
Other diseases, besides type 2 diabetes, influencing carbohydrate metabolism

Arm && Interventions

Group	Intervention	Description
10 mg (+)-epicatechin	(+)-Epicatechin	4 subjects randomized to one dose of 10 mg (+)-epicatechin taken orally
30 mg (+)-epicatechin	(+)-Epicatechin	4 subjects randomized to one dose of 30 mg (+)-epicatechin taken orally
100 mg (+)-epicatechin	(+)-Epicatechin	4 subjects randomized to one dose of 100 mg (+)-epicatechin taken orally

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Circulating Urinary Concentrations of Intact Epicatechin and Epi Metabolites	Baseline and 24 hours	This will be initial PK study on synthetic (+)-epicatechin in humans. Circulating and urinary concentrations of intact epicatechin and epicatechin metabolites, including specific enantiomers

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Major Safety Endpoints	Baseline and 24 hours	Clinically significant differences in the major safety endpoints are defined as: BP (10 mm Hg change), HR (10 bpm), creatinine (\>1.5 ULN), and highly conservative changes in alkaline phosphatase and liver transaminases (\>1.5 ULN).
Change From Baseline in Circulating Glucose Concentrations (mg/dL*24hr)	Baseline and 24 hours
Change From Baseline in Circulating Insulin Concentrations (uU/mL*24hr)	Baseline and 24 hours
Change From Baseline in Circulating C-Peptide Concentrations (ng/mL*24hr)	Baseline and 24 hours