Beneficial Effects of Quercetin in Chronic Obstructive Pulmonary Disease (COPD)

In our preclinical study, we have demonstrated that 4 fold increase in plasma quercetin
levels significantly decreased lung inflammation and prevented progression. Clinical studies
in healthy volunteers 4 fold increase in plasma quercetin levels (0.22 to 1 µM) could be
achieved by supplementing with 500mg of quercetin/day. However, safety of quercetin
supplementation and quercetin dose required to achieve 4 fold increases in plasma quercetin
levels in 'at-high-risk' COPD population is yet to be established. This study involves two
phases; the first phase examines the safety of quercetin supplementation in subjects with
chronic obstructive pulmonary disease (COPD) and the second phase determines the efficacy of
quercetin in COPD patients. In this study, we will enroll COPD patients with mild to
moderate disease between the age group of 40 to 65 years. During the first phase, we will
enroll a total of 9 patients to examine the tolerance and safety of three doses of quercetin
(500, 1000 and 2000 mg/day) in a dose escalation manner. First cohort consisting of three
subjects will receive placebo or 500 mg of quercetin per day for one week and the safety of
quercetin supplementation will be assessed by monitoring adverse events and any changes in
outcomes of blood test that include complete blood counts (CBC)and comprehensive metabolic
panel prior to after supplementation. If this dose is safe and tolerated, second cohort of 3
subjects will receive placebo or 1000 mg of quercetin per day quercetin for one week and
again safety will be assessed. If the dose is safely tolerated, the third cohort will
receive either placebo or 2000 mg of quercetin per day for a week and the safety will be
assessed. Based on this initial study, we will choose the highest quercetin dose tolerated
with no adverse events and the dose (500 mg of quercetin per day) that was found to increase
plasma quercetin levels by 4 fold over baseline in healthy volunteers to examine the
efficacy of quercetin in reducing inflammatory and oxidative stress markers and improving
lung function in COPD subjects. In the second phase, we will enroll a total of 75 subjects
and randomized into three arms; placebo (15 subjects) or one of the two doses of quercetin
(30 subjects per arm). All enrolled subjects will be asked to avoid quercetin rich foods
throughout the study period. One week after enrollment (run-in), subjects will be either
supplemented with either placebo or one of the two doses of quercetin for 4 weeks. All
participants will be blinded for study agents. Plasma and sputum quercetin levels, lung
function, and markers of oxidative stress and inflammation will be determined at the start
of the study (following run-in period), at the end of 4 weeks treatment period.

Inclusion Criteria:

- Subjects diagnosed with mild to moderate COPD (GOLD stage I, II and III)-

- 10 pack-year smoking history or greater and ceased to smoke at least for 2 months
prior to recruitment

- Subjects taking H2 antagonists, Imodium or loratadine and willing to stop during the
study period

Exclusion criteria:

- COPD subjects with >80% or <35% predicted

- Current smokers

- Known allergy/sensitivity to quercetin

- Subjects with primary diagnosis of asthma

- Upper respiratory tract infection within two weeks of the screening visit

- Acute bacterial infection requiring antibiotics within two weeks of screening

- Emergency treatment or hospitalization within one month of screening

- Pregnant or lactating mothers

- Women who don't consent to take pregnancy test

- Unwillingness to stop flavonoid supplementation

- Dietary intake exceeding or averaging 150 mg quercetin daily as assessed by
Bioflavonoid Food and Supplement Screener

- Daily oral steroid treatment, warfarin, cyclosporine (neural, sandimmune), digoxin,
fexofenadine, paclitaxel, diltiazem, saquinavir, selected chemotherapeutic agents
(etoposide, vinblastine, vincristine, vindesine), antifungals (ketoconazole,
itraconazole), protease inhibitors (amprenavir, indinavir, nelfinavir), verapamil,
oral glucocorticoids, erythromycin, quinidine

- Subjects taking H2 antagonists (cimetidine, ranitidine), loperamide (Imodium) or
loratadine and not willing to stop during study period

- Lung cancer history or undergoing chemo- or radiation therapy

- Inflammatory bowel disease

- Child bearing age, who are unwilling to use adequate contraception or abstain during
the course of the study.