Beneficial Effects of Quercetin in Chronic Obstructive Pulmonary Disease (COPD)
Condition: Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Study type: Interventional
Phase: Phase 1

Summary: 
      Chronic obstructive pulmonary disease (COPD) is a progressive disorder of the lung parenchyma
      and airways, which is the third-leading cause of death in the USA. Current therapies for COPD
      are only partially effective and may also have side effects. Although increasing evidence
      indicates that quercetin supplementation may be beneficial in treating COPD, key
      methodological issues have not been resolved. The overall objective of this study is to
      determine the dosage of quercetin supplementation, bioavailability of quercetin, safety,
      dose-response relationship and appropriate biomarkers which reflect clinical outcomes in
      patients with COPD that is necessary for conducting large clinical trials in this patient
      population.
    

Detailed description: 
      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.

      Having completed Phase I study at University of Michigan, we planned to do the Phase II
      efficacy study under separate NCT number. As of 2016 this phase II study has not begun. Based
      on the initial study, we plan to 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.

      Three of the original outcome measures listed related to this follow up study of 4 weeks
      treatment which was never begun. Therefore they have been deleted.
    

Intervention name(s): Quercetin; Placebo - sugar chew
Intervention type(s): Drug; Other
Intervention description(s): COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take one of the following for 1 week
Quercetin 500 mg/350 mg of vitamin C and 10 mg niacin
Quercetin 1000 mg/350 mg of vitamin C and 10 mg niacin
Quercetin 2000 mg/350 mg of vitamin C and 10 mg niacin; COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take placebo (sugar chew containing 350 mg of vitamin C and 10 mg niacin)
Other intervention name(s): QB3C without folic acid
Intervention MeSH terms: Folic Acid; Quercetin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: COPD; Emphysema; chronic bronchitis; Quercetin; flavonoids