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View Clinical Trial (Medical Research Study)
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Effect of EGCG on the Body's Response to Insulin - NCT00434499-20892 (Clinical Trial 162531)
Permalink: http://www.ClinicalConnection.com/exp/ExpandedPatientViewStudy162531.aspx
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| City: |
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Bethesda |
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State:
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MD |
| Zip Code: |
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20892 |
| Conditions: |
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Hypertension - Obesity - Type 2 Diabetes - Insulin Resistance |
| Purpose: |
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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, people with high
blood pressure (HBP), and people with type 2 diabetes. Insulin is not as effective in people
who are overweight, have HBP 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, people with HBP and people with type 2 diabetes
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
- Blood sugar checks for patients with diabetes
- 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.
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| Study summary: |
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Green tea is a functional food whose consumption is associated with improved cardiovascular
morbidity and mortality in several large epidemiological studies. One third of the solids
in green tea are composed of the bioactive polyphenol epigallocatechin 3-gallate (EGCG).
Studies in both cell- and animal-based models (from our lab and elsewhere) suggest that EGCG
may mimic and/or augment beneficial metabolic, vascular, and anti-inflammatory actions of
insulin. Indeed, we have recently shown that 3-week EGCG therapy of SHR rats (genetic model
of hypertension with features of human metabolic syndrome including insulin resistance,
hyperinsulinemia, endothelial dysfunction, and overweight) lowers blood pressure, improves
endothelial dysfunction, increases insulin sensitivity, and raises adiponectin levels nearly
as effectively as treatment with the conventional ACE-inhibitor enalapril. Obesity, type 2
diabetes, and hypertension are all important interrelated public health problems that are
characterized by reciprocal relationships between insulin resistance and endothelial
dysfunction. Thus, therapies for these diseases that improve insulin resistance often
simultaneously improve endothelial function and vice versa. Based on results from cellular,
physiological, and epidemiological studies, we hypothesize that oral EGCG administration
will simultaneously ameliorate insulin resistance and lower blood pressure in human subjects
with obesity, essential hypertension, or type 2 diabetes. To test these hypotheses, we will
conduct a randomized, placebo-controlled, double-blind, cross-over study to evaluate
potential beneficial effects of EGCG to modulate insulin sensitivity, blood pressure,
vascular function, and inflammatory markers in four groups of subjects (lean healthy
controls, obesity, essential hypertension, or type 2 diabetes). After a 2-week EGCG-free
run-in period, each subject will be randomized to receive EGCG or placebo capsules (400 mg
p.o. B.I.D.) for 4 weeks. This will be followed by a 2-week EGCG-free washout period after
which subjects will cross-over to the other treatment arm. At baseline, and after each
4-week treatment period, we will assess insulin sensitivity (hyperinsulinemic isoglycemic
glucose clamp technique) and vascular function. Regarding vascular function, we will
measure basal and insulin-stimulated brachial artery blood flow (large conduit artery
assessed by Doppler ultrasound) as well as capillary recruitment in forearm skeletal muscle
(small nutritive arterioles assessed by ultrasound with microbubble contrast). Blood
pressure will be measured weekly in the NIH CRC throughout the duration of the study. EGCG
pharmacokinetics will be measured at the beginning of each glucose clamp study day after
oral administration of a single dose of EGCG or placebo. Finally, various plasma markers of
inflammation will be measured at baseline and at the end of each treatment arm to evaluate
potential changes that may be related to improvements in metabolic and/or vascular function.
This study will explore whether EGCG, a single compound thought to be a major bioactive
component of green tea, is effective at improving insulin resistance and lowering blood
pressure in subjects with obesity, hypertension, or diabetes. Results from this study may
have important implications for understanding potential health benefits of functional foods
that contain bioactive polyphenols including green tea, dark chocolate, and red wine. |
| Criteria: |
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- INCLUSION CRITERIA:
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).
HYPERTENSIVE SUBJECTS:
Men and women between the ages of 21-65 years of age who are in good general health except
for mild to moderate hypertension with seated blood pressure between 140/90 and 160/100 mm
of Hg while off of anti-hypertensive medications (average over 3 visits).
TYPE 2 DIABETIC SUBJECTS:
Men and women between the ages of 21-65 years of age in good general health except for
type 2 diabetes controlled with diet and/or oral hypoglycemic agents (except
thiazolidinediones) with a HbA(1c) between 6-9% and C-peptide levels greater than 0.8
ng/ml.
EXCLUSION CRITERIA:
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.
Children are excluded from this study because children do not typically take EGCG and do
not typically have hypertension or type 2 diabetes mellitus.
DIABETIC SUBJECTS:
In addition to the above general exclusion criteria, we will exclude diabetic subjects
with type 1 diabetes mellitus, poorly controlled diabetes (HbA1c greater than 9.0%),
random blood glucose greater than 300 mg/dL, symptomatic hyperglycemia (symptoms of
dehydration or acidosis), the presence of hypertension, proliferative retinopathy, or
diabetic neuropathy.
HYPERTENSIVE SUBJECTS:
In addition to the above general exclusion criteria, we will exclude hypertensive subjects
if they have diabetes. |
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| Study is available at: |
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National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, MD 20892
United States
Primary Contact:
Patient Recruitment and Public Liaison Office
Email: prpl@mail.cc.nih.gov
Phone: (800) 411-1222 |
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If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
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| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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November 15, 2009 |
Modifications to
this listing: |
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Only selected fields are shown, please use the link
above to view all information about this clinical trial. |
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Clinical trials are medical research studies designed to test the safety and/or
effectiveness of new drugs, devices, or treatments in humans. These studies are
conducted worldwide for a range of conditions and illnesses. Learn more about
clinical research and participating in a study at
About Clinical Trials.
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