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

This will be a double-blind, randomized, placebo-controlled, single dose study of (+)- epicatechin with one 30mg dose/day for a total of 7 days

Study Overview

• Status: Completed
• Conditions: Pre-diabetes
• Intervention / Treatment: Drug: epicatechin; Drug: Placebo

Detailed Description

This project is a double-blinded, placebo-controlled, randomized, Phase I study that will include (+)-epicatechin dosing over seven days.

• Subjects will meet the American Diabetes Association (ADA) criteria for pre-diabetes, including impaired fasting glucose (IFG) [refer to inclusion/exclusion criteria].
• The Project includes: 7 day evaluation of a single daily dose of synthetic (+)-epicatechin in pre-diabetic individuals as compared to placebo.
• The Project has 4 outpatient clinic study visits: screening (Visit 1), randomization (Visit 2), end of study drug (Visit 3), follow up end of study (Visit 4).
• This Project has 2 telephone visits

Primary hypothesis: As these studies are designed to evaluate safety and tolerability, there is no primary hypothesis to test.

Primary outcome measures. Vital signs and safety labs: BP, HR, creatinine, alkaline phosphatase, and liver transaminases

These studies will provide initial data about if (+)-epicatechin can influence glycemic control in individuals with prediabetes.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92161
      • VA San Diego Healthcare System
    • San Diego, California, United States, 92161
      • CMR Center for Metabolic Research VASDHS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pre-diabetic based on medical history and screening results
• 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 female 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 prior to screening
• Body Mass Index (BMI) > 27 kg/m2
• Definition of pre-diabetes: impaired fasting glucose (IFG, fasting glucose = 100-125 mg/dL) and/OR 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 upper limit of normal (ULN)), determined in the last 6 months by a certified clinical laboratory
• Recent myocardial infarct 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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: (+)-epicatechin 30mg; 10 subjects will be randomized to a 30mg dose of synthetic (+)-epicatechin	Drug: epicatechin; 30 mg (+)-epicatechin, taken orally, one pill/day in the morning; Other Names: 122158
Placebo Comparator: placebo; 5 subjects will be randomized to a placebo	Drug: Placebo; Placebo pill, taken orally, one pill/day in the morning

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in major safety endpoints: Blood Pressure (BP)	Clinically significant differences in the major safety endpoints are defined as: BP (10 mm Hg change)	Baseline and Day 7
Change from baseline in major safety endpoints: Heart Rate (HR)	Clinically significant differences in the major safety endpoints are defined as: HR (10 bpm)	Baseline and Day 7
Change from baseline in major safety endpoints: Kidney Function	Clinically significant differences in the major safety endpoints are defined as: creatinine (>1.5 ULN)	Baseline and Day 7
Change from baseline in major safety endpoints: Hepatic Function	Clinically significant differences in the major safety endpoints are defined as: highly conservative changes in alkaline phosphatase and liver transaminases (>1.5 ULN)	Baseline and Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline: Glucose	Change from baseline of glucose (mg/dL) as measured from fasting labs collected at Visits 2 and 3.	Baseline and Day 7
Change from baseline: Insulin	Change from baseline of insulin (uIU/ml) as measured from fasting labs collected at Visits 2 and 3.	Baseline and Day 7
Change from baseline: C-Peptide	Change from baseline of C-Peptide (ng/mL) as measured from fasting labs collected at Visits 2 and 3.	Baseline and Day 7

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, 2015
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: January 7, 2016
• First Submitted That Met QC Criteria: January 12, 2016
• First Posted (Estimate): January 14, 2016

Study Record Updates

• Last Update Posted (Estimate): April 28, 2016
• Last Update Submitted That Met QC Criteria: April 26, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: pre-diabetes; epicatechin
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hyperglycemia; Prediabetic State; Glucose Intolerance
• Other Study ID Numbers: 08847002; 1R01AT008310-01 (U.S. NIH Grant/Contract)