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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)


Phase 2
40 Years
80 Years
Open (Enrolling)
Both
Lung Cancer, Pulmonary Complications

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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 - TucsonTucson, Arizona  85723
Arizona Cancer Center at University of Arizona Health Sciences CenterTucson, Arizona  85724
Virginia G. Piper Cancer Center at Scottsdale Healthcare - SheaScottsdale, Arizona  85260