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

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

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

Study Overview

• Status: Completed
• Conditions: Pre-diabetes
• Intervention / Treatment: Drug: (+)-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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92161
      • VA San Diego Healthcare System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 10 mg (+)-epicatechin; 4 subjects randomized to one dose of 10 mg (+)-epicatechin taken orally	Drug: (+)-Epicatechin; The drug to be tested is (+)-epicatechin, synthesized under GMP standards. Subjects will be given a single oral dose of (+)- epicatechin and followed on an inpatient basis over 24 hours. Three (3) different dose levels will be tested in a randomized, double-blind design: (+)- epicatechin 10 mg, 30 mg, or 100 mg. As this is a pilot study, a placebo arm will not be included.; Other Names: Epicatechin
Experimental: 30 mg (+)-epicatechin; 4 subjects randomized to one dose of 30 mg (+)-epicatechin taken orally	Drug: (+)-Epicatechin; The drug to be tested is (+)-epicatechin, synthesized under GMP standards. Subjects will be given a single oral dose of (+)- epicatechin and followed on an inpatient basis over 24 hours. Three (3) different dose levels will be tested in a randomized, double-blind design: (+)- epicatechin 10 mg, 30 mg, or 100 mg. As this is a pilot study, a placebo arm will not be included.; Other Names: Epicatechin
Experimental: 100 mg (+)-epicatechin; 4 subjects randomized to one dose of 100 mg (+)-epicatechin taken orally	Drug: (+)-Epicatechin; The drug to be tested is (+)-epicatechin, synthesized under GMP standards. Subjects will be given a single oral dose of (+)- epicatechin and followed on an inpatient basis over 24 hours. Three (3) different dose levels will be tested in a randomized, double-blind design: (+)- epicatechin 10 mg, 30 mg, or 100 mg. As this is a pilot study, a placebo arm will not be included.; Other Names: Epicatechin

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Major Safety Endpoints	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).	Baseline and 24 hours
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

Collaborators and Investigators

• Sponsor: Veterans Medical Research Foundation
• Collaborators: University of California, San Diego; National Institutes of Health (NIH); National Center for Complementary and Integrative Health (NCCIH); San Diego Veterans Healthcare System
• Investigators: Principal Investigator: Robert R Henry, MD, San Diego Veterans Healthcare System

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: December 23, 2014
• First Submitted That Met QC Criteria: December 30, 2014
• First Posted (Estimate): January 1, 2015

Study Record Updates

• Last Update Posted (Actual): April 17, 2017
• Last Update Submitted That Met QC Criteria: March 3, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Prediabetic State
• Other Study ID Numbers: 08847; 1R01AT008310-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO