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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

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

Conditions
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Pre-diabetes

Intervention / Treatment
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* Drug: epicatechin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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epicatechin, pre-diabetes