Effect of EGCG on the Body's Response to Insulin

NCT00434499 | Withdrawn Phase 2 DMC

• 1 other identifier: HP-00048859
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine whether epigallocatechin gallate (EGCG), a major component of green tea, affects how the body responds to insulin in healthy and obese people. Insulin is not as effective in people who are overweight, have high blood pressure or diabetes. This condition is known as insulin resistance. Laboratory studies suggest that green tea or EGCG treatment lowers blood pressure, lowers blood sugar and increases blood flow. This study will see if EGCG improves insulin resistance or insulin's effects on blood flow in people with insulin resistance. Healthy normal weight or overweight people between 21 and 65 years of age may be eligible for this study. Participants are randomly assigned to take EGCG or a placebo ( inactive dummy pill ) in two 4-week treatment phases with a 2-week period of no study medication before each treatment phase. After the first 4-week treatment, patients on placebo are switched to EGCG and those on EGCG are switched to placebo. In addition to treatment, participants undergo the following procedures during the study period:

• Screening, including medical history, physical examination and blood and urine tests, and finger-stick blood sugar measurement for patients with diabetes
• Complete a dietary and physical activity questionnaire and consult with a dietitian
• Blood and urine tests
• At-home and clinic blood pressure monitoring
• Glucose clamp test to measure how the body responds to insulin. This test is done three times during the study. A needle is placed in a vein in each of the subject's arms, one for sampling blood and the other for infusing insulin, glucose and potassium. Glucose and insulin levels, electrolytes, lipids, fatty acids, cytokines and epicatechin are measured.
• Forearm blood flow measurement with microbubbles and ultrasound. Before beginning the glucose clamp test, a test of how well the blood vessels relax is done. A device that measures the size of the artery in the upper arm is placed above the elbow. Blood flow in the muscle of the forearm is measured by ultrasound using a small infusion through a vein of microbubble contrast agent consisting of gas-filled bubbles the size of red blood cells. The contrast agent is infused over a 7- to 9-minute period at the beginning of the glucose clamp test and again 2 hours after the beginning of the test.

Conditions

Hypertension; Obesity; Type 2 Diabetes; Insulin Resistance

Keywords

Green Tea; Insulin Resistance; Endothelial Dysfunction; Nitric Oxide; Inflammation; Obesity; Overweight; Diabetes Type 2; High Blood Pressure; Healthy Volunteer; HV

Outcome Measures

Primary Outcomes (1)

• Improvement in insulin resistance

  measurements of insulin resistance prior to study drug, after 4 weeks of EGCG or placebo and at end of study

  14 weeks

Secondary Outcomes (1)

• Improvement in endothelial dysfunction

  14 weeks

Study Arms (2)

placebo first

ACTIVE COMPARATOR

placebo first then crossover to EGCG

Drug: EGCG

EGCG first

ACTIVE COMPARATOR

EGCG first then crossover to placebo

Drug: EGCG

Interventions

EGCG DRUG

EGCG 400 mg by mouth twice/daily for 4 weeks duration.

EGCG first; placebo first

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HEALTHY SUBJECTS:
• Men and women in good general health with no significant underlying illnesses who are between the ages of 21-65 years of age with HbA(1C) less than 6.5%, fasting blood glucose less than 100 mg/dL, blood pressure less than 120/80, and BMI between 20-25 kg/m(2). Subjects should have never smoked tobacco or not smoked within the previous year.
• OBESE SUBJECTS:
• Men and women in good general health with no significant underlying illnesses except obesity who are between the ages of 21-65 years of age with HbA(1C) less than 6.5%, fasting blood glucose less than 110 mg/dl, blood pressure less than 140/90, and BMI between 30-40 kg/m(2).

You may not qualify if:

• ALL SUBJECTS:
• Subjects will be excluded from our study if they are pregnant , breastfeeding or if they plan pregnancy prior to the end of the study.
• In addition, subjects will be excluded if their age is greater than 65 yrs, BMI greater than or equal to 40 kg/m(2), or have liver disease (including liver transaminase levels greater than twice the upper limit of normal), pulmonary disease, renal insufficiency (serum creatinine greater than 2.0 mg/dl), coronary heart disease, heart failure (New York Heart Association heart failure Class III or IV), peripheral vascular disease, coagulopathy, major depressive disorder, actively smoking or used tobacco within the last year, history of cancer, in treatment for any form of cancer, positive tests for HIV, hepatitis B or C, or take systemic corticosteroids, thiazolidinediones (within 3 months), insulin, or anticoagulants, use food supplements that cannot be discontinued, regular intake of 8 or more cups of tea per week within 3 months prior to study entry, regular alcoholic beverage intake of more than two drinks per day (a drink corresponds to approximately 12 ounces of beer, 4 ounces of table wine, and between 1 and 1.5 ounces of 80-proof spirits), poor compliance during run-in period or regular use of medications that affect insulin sensitivity, blood pressure or vascular function and that cannot be discontinued.
• In addition, history of any other medical disease, laboratory abnormalities, or psychological conditions that would make the subject (based upon the principal investigator's judgment) unsuitable for study enrollment.
• Subjects with known hypersensitivity to octafluoropropane, recent eye surgery, or with known cardiac shunts will also be excluded from participating because of potential adverse effects from microbubble contrast agent.
• Subjects will be excluded if they are unable to give informed consent for all procedures.
• Currently, type 2 diabetes is not rare in children, however children are excluded from this study because children do not typically take EGCG and do not typically have hypertension or type 2 diabetes mellitus.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Related Publications (3)

• Jemal A, Ward E, Hao Y, Thun M. Trends in the leading causes of death in the United States, 1970-2002. JAMA. 2005 Sep 14;294(10):1255-9. doi: 10.1001/jama.294.10.1255.

  PMID: 16160134 BACKGROUND

• Must A, Spadano J, Coakley EH, Field AE, Colditz G, Dietz WH. The disease burden associated with overweight and obesity. JAMA. 1999 Oct 27;282(16):1523-9. doi: 10.1001/jama.282.16.1523.

  PMID: 10546691 BACKGROUND

• Fox CS, Coady S, Sorlie PD, Levy D, Meigs JB, D'Agostino RB Sr, Wilson PW, Savage PJ. Trends in cardiovascular complications of diabetes. JAMA. 2004 Nov 24;292(20):2495-9. doi: 10.1001/jama.292.20.2495.

  PMID: 15562129 BACKGROUND

MeSH Terms

Conditions

Hypertension; Obesity; Diabetes Mellitus, Type 2; Insulin Resistance; Inflammation; Overweight

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism; Pathologic Processes

Study Officials

• Kashif Munir, MD

  University of Maryland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: February 10, 2007
• First Posted: February 13, 2007
• Study Start: February 1, 2007
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: March 4, 2022

Record last verified: 2022-02

Locations

US (1)