Chemoprevention of Lung Carcinogenesis Using Green Tea: Phase IIb Randomized, Double-Blinded, Placebo Controlled Trial of Green Tea and Polyphenon E in Former Smokers With Chronic Obstructive Lung Disease (COPD)
40 Years
80 Years
Both
Lung Cancer, Pulmonary Complications
Trial Information
Chemoprevention of Lung Carcinogenesis Using Green Tea: Phase IIb Randomized, Double-Blinded, Placebo Controlled Trial of Green Tea and Polyphenon E in Former Smokers With Chronic Obstructive Lung Disease (COPD)
OBJECTIVES:
Primary
- Evaluate the effects of high-level oral consumption of defined green tea (four 12-oz
servings/day) or polyphenon E capsules (4 capsules/day) on markers of cellular
oxidative damage, as measured by 8-hydroxydeoxyguanosine (8-OHdG) and
8-F_2-isoprostanes (8-epi-PGF2) in former smokers with chronic obstructive pulmonary
disease.
Secondary
- Evaluate the effects of high-level oral consumption of defined green tea or polyphenon
E capsules on body antioxidant status (carotenoids, vitamins A and E, ascorbic acid
[vitamin C] and antioxidant enzymes [catalase and glutathione peroxidase]) in blood in
these patients.
- Evaluate the effects of high-level oral consumption of defined green tea or polyphenon
E capsules on gene expression of markers of proliferation (epidermal growth factor
receptor [EGFR], proliferating cell nuclear antigen [PCNA], JUN, FOS, and Ki-67) and
apoptosis (bcl-2 and caspase 3) in induced sputum in these patients.
Tertiary
- Evaluate the effects of high-level oral consumption of defined green tea or polyphenon
E capsules on lung function, in terms of FEV_1 and FVC improvement, in these patients.
- Evaluate the relative adherence to use of green tea beverage vs polyphenon E capsules
in these patients.
OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are
stratified according to gender and inhaled steroid usage (yes vs no).
All patients receive placebo tea beverage and placebo capsules 4 times a day for 2 weeks.
Patients are randomized to 1 of 3 treatment arms after successful completion of the 2-week
period.
- Arm I (green tea beverage): Patients receive oral green tea beverage and oral
polyphenon E placebo daily for 6 months.
- Arm II (green tea capsule [polyphenon E]): Patients receive oral green tea beverage
placebo and oral polyphenon E daily for 6 months.
- Arm III (placebo): Patients receive oral green tea beverage placebo and oral polyphenon
E placebo daily for 6 months.
Patients undergo blood, urine, exhaled breath condensate (EBC), induced sputum, and buccal
cell collection at baseline and periodically during study for biomarker/laboratory analysis.
Blood samples are analyzed for 8-hydroxydeoxyguanosine (8-OHdG), glutathione peroxidase, and
catalase. Urine is examined for F_2-isoprostanes, 8-OHdG, and tea polyphenols. Induced
sputum bronchoepithelial cells are analyzed for gene expression of genes implicated in
cellular growth and apoptotic pathway (i.e., epidermal growth factor receptor [EGFR],
proliferating cell nuclear antigen [PCNA], JUN, FOS, Ki-67, bcl-2, and caspase 3) via
reverse transcriptase-polymerase chain reaction. EBC samples are examined for
F_2-isoprostane levels. Buccal cells are stored for future analysis.
PROJECTED ACCRUAL: A total of 195 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of chronic obstructive pulmonary disease
- FEV_1/FVC ≤ 78
- History of smoking ≥ 1 pack daily for 30 years OR 2 packs daily for 15 years
- Stopped smoking for ≥ 1 year
- No previously diagnosed bronchiectasis
- No history of > 1 acute emphysema exacerbation within the past 3 months
PATIENT CHARACTERISTICS:
- ECOG performance status 0-1
- WBC ≥ 3,500/mm³
- Platelet count > 130,000/mm³
- Hemoglobin ≥ 11 g/dL (female) or 12 g/dL (male)
- AST and ALT normal
- Bilirubin ≤ 1.5 mg/dL (unless Gilbert's disease present)
- Creatinine ≤ 1.5 mg/dL
- Alkaline phosphatase ≤ 2 times upper limit of normal
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No invasive cancer within the past 5 years
- Able and willing to consume caffeinated beverages
- Able to produce induced sputum
- Able to perform forced expiratory maneuver during spirometry testing
- No immunosuppression by virtue of medication or disease including, but no limited to,
any of the following:
- Organ transplantation
- Liver or kidney failure
- Autoimmune diseases
- Oral steroids
- Chemotherapy
- No serious concurrent illness that could preclude study compliance, such as
uncontrolled high blood pressure, heart disease, or poorly controlled diabetes
- No myocardial infarction within the past 6 weeks
PRIOR CONCURRENT THERAPY:
- At least 2 weeks since prior and no concurrent dietary supplements or herbal
products, including any of the following:
- Herbal tea
- Ginkgo biloba > 60 mg/day
- Melatonin > 3 mg/day
- Echinacea > 300 mg/day
- Hypericum perforatum (St. John's wort) > 300 mg/day
- DHEA mustard > 5 mg/day
- At least 2 weeks since prior and no concurrent nontrial tea or tea products
- More than 3 weeks since prior chest or abdominal surgery
- More than 3 months since prior participation in chemoprevention or clinical
intervention trials
- At least 3 months since prior and no concurrent megadoses of vitamins, defined as >
4,000 IU of vitamin A, 400 IU of vitamin E, 400 IU of cholecalciferol (vitamin D), 60
μg of selenium, or 1,000 mg of ascorbic acid (vitamin C) per day
- No regular consumption of ≥ 6 cups or glasses of tea per week
- No concurrent nontrial caffeine at > 1 serving/day (1 serving defined as 12 oz of
regular soda or 8 oz of coffee)
- No concurrent participation in another interventional clinical trial
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Prevention
Outcome Measure:
Biomarkers of cellular oxidative damage
Safety Issue:
No
Principal Investigator
Iman Hakim, MD, PhD, MPH
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of Arizona
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000487501
NCT ID:
NCT00363805
Start Date:
May 2004
Completion Date:
Related Keywords:
- Lung Cancer
- Pulmonary Complications
- small cell lung cancer
- non-small cell lung cancer
- pulmonary complications
- Lung Diseases
- Pulmonary Disease, Chronic Obstructive
- Lung Neoplasms
- Lung Diseases, Obstructive
Name | Location |
|---|---|
| Veterans Affairs Medical Center - Tucson | Tucson, Arizona 85723 |
| Arizona Cancer Center at University of Arizona Health Sciences Center | Tucson, Arizona 85724 |
| Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea | Scottsdale, Arizona 85260 |
