Biological Effects of Quercetin in COPD Phase II

Study Overview
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Brief Summary
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This study determines whether quercetin supplementation reduces the inflammation and oxidative stress markers in patients with chronic obstructive pulmonary disease. It is small study with 8 subjects receiving quercetin 1000 mg/day, 8 patients receiving 500 mg/day and 4 subjects receive placebo.

Detailed Description
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Chronic obstructive pulmonary disease (COPD) is a progressive lung disorder and affects millions of people globally. Although the exact mechanisms of pathogenesis of this disease are not well-understood, the general consensus is that oxidative stress and inflammation induced by exposure to cigarette smoke or other environmental or occupational hazards are responsible for development of COPD. Therefore, therapies aimed at decreasing oxidative stress and inflammation constitutes an important component of treating COPD. The current pharmacological therapies may provide temporary symptom relief, reduce acute exacerbations and hospitalizations, but are associated with side effects. Therefore complementary method of treatment with potentially fewer side effects and relatively well-tolerated provide promising alternative. One such compound is quercetin, which is plant polyphenol and is present in variety of foods that we consume. Quercetin has potent antioxidant and anti-inflammatory properties and reduces oxidative stress and inflammation in a preclinical model of COPD. Quercetin exerts it antioxidant properties not only by neutralizing free radical species, but also by enhancing the expression of antioxidant enzymes. Similarly, quercetin inhibits various protein and lipid kinases by competing for adenosine triphosphate (ATP) binding sites thus reducing the inflammatory pathways.

Official Title
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Effects of Quercetin on the Oxidative Stress and Inflammatory Markers in COPD Phase II

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Quercetin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with COPD, 40 - 80 yrs of age Post-bronchodilator forced expiratory volume (FEV)1/forced vital capacity (FVC) ratio 0.7, FEV1% predicted between 40 to 70 Both active and ex-smokers with at least 10 pack-years history of smoking COPD patients taking H2 antagonists, loperamide or loratadine and willing to stop during the study period Exclusion Criteria: Known allergy/sensitivity to quercetin Subjects with primary current 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 for any reasons Unwillingness to stop flavonoid supplementation Dietary intake exceeding or averaging 150 mg quercetin daily as assessed by Bioflavonoid Food and Supplement Screener Daily warfarin or cyclosporine (Neoral, Sandimmune) 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 Subjects with no detectable levels of inflammatory CRP or SP-D in blood and/or IL- 1β or 8-isoprostane in the exhaled breath condensate Women of child-bearing age and unwilling to take pregnancy test Child-bearing age, who are unwilling to use adequate contraception or abstain during the course of the study. Pregnant or lactating mothers

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double blinded placebo controlled study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Quercetin 1000 mg/day<br>Quercetin 1000 mg/day Quercetin is provided as caplet and each caplet will have 500 mg of quercetin Quercetin will be administered orally twice daily, one half dose (1 caplet) in the morning after breakfast and one half dose (1 caplet) in the evening after dinner for six months. | Drug: Quercetin<br>* Placebo<br>* Other names: Placebo;|
| Active Comparator: Quercetin 500mg/day<br>Quercetin 500 mg/day Quercetin is provided as caplet and each caplet will have 500 mg of quercetin Quercetin will be administered orally once daily, (1 caplet) in the morning after breakfast and matching placebo in the evening after dinner for six months. The placebo is added to match the number of caplets with 1000 mg/day arm | Drug: Quercetin<br>* Placebo<br>* Other names: Placebo;|
| Placebo Comparator: Placebo<br>Placebo is also provided as caplets that is similar to quercetin in color, taste and texture and will contain all the stabilizers and the inactive ingredients that is present in the quercetin chews. Placebo will be administered orally twice daily, one half dose (1caplet) in the morning after breakfast and one half dose (1 caplet) in the evening after dinner for six months. | Drug: Quercetin<br>* Placebo<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxidative stress markers | 8-isoprostane | six months | 
| Inflammatory markers | Interleukin (IL)-1beta, IL-8, in bronchoalveolar lavage and C-reactive protein (CRP) and surfactant protein (SP)-D in serum | six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quercetin | Levels of quercetin in blood and lung | six months |