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

Chronic Obstructive Pulmonary Disease Clinical Trial

— Quercetin  

Official title:

Phase I/II Study to Determine the Safety and Efficacy of Quercetin in COPD Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01708278
• Other study ID #: HUM000061735
• Secondary ID: R21AT007357
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 10, 2012
• Last updated: January 20, 2016
• Start date: February 2014
• Est. completion date: October 2015

Study information

• Verified date: January 2016
• Source: University of Michigan
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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. 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.

Other known NCT identifiers

• NCT02013440

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: October 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 80 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Quercetin
COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take Placebo containing 350 mg of vitamin C and 10 mg niacin or one of the two doses of quercetin twice a day for 4 weeks

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan

Sponsors (3)

Lead Sponsor	Collaborator
University of Michigan	National Institutes of Health (NIH), Quercegen Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (10)

Bischoff SC. Quercetin: potentials in the prevention and therapy of disease. Curr Opin Clin Nutr Metab Care. 2008 Nov;11(6):733-40. doi: 10.1097/MCO.0b013e32831394b8. Review. — View Citation

Boots AW, Drent M, de Boer VC, Bast A, Haenen GR. Quercetin reduces markers of oxidative stress and inflammation in sarcoidosis. Clin Nutr. 2011 Aug;30(4):506-12. doi: 10.1016/j.clnu.2011.01.010. Epub 2011 Feb 15. — View Citation

Boots AW, Wilms LC, Swennen EL, Kleinjans JC, Bast A, Haenen GR. In vitro and ex vivo anti-inflammatory activity of quercetin in healthy volunteers. Nutrition. 2008 Jul-Aug;24(7-8):703-10. doi: 10.1016/j.nut.2008.03.023. — View Citation

Comstock AT, Ganesan S, Chattoraj A, Faris AN, Margolis BL, Hershenson MB, Sajjan US. Rhinovirus-induced barrier dysfunction in polarized airway epithelial cells is mediated by NADPH oxidase 1. J Virol. 2011 Jul;85(13):6795-808. doi: 10.1128/JVI.02074-10. Epub 2011 Apr 20. — View Citation

Ganesan S, Faris AN, Comstock AT, Chattoraj SS, Chattoraj A, Burgess JR, Curtis JL, Martinez FJ, Zick S, Hershenson MB, Sajjan US. Quercetin prevents progression of disease in elastase/LPS-exposed mice by negatively regulating MMP expression. Respir Res. 2010 Sep 28;11:131. doi: 10.1186/1465-9921-11-131. — View Citation

Ganesan S, Faris AN, Comstock AT, Wang Q, Nanua S, Hershenson MB, Sajjan US. Quercetin inhibits rhinovirus replication in vitro and in vivo. Antiviral Res. 2012 Jun;94(3):258-71. doi: 10.1016/j.antiviral.2012.03.005. Epub 2012 Mar 23. — View Citation

Harwood M, Danielewska-Nikiel B, Borzelleca JF, Flamm GW, Williams GM, Lines TC. A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food Chem Toxicol. 2007 Nov;45(11):2179-205. Epub 2007 Jun 7. Review. — View Citation

Jin F, Nieman DC, Shanely RA, Knab AM, Austin MD, Sha W. The variable plasma quercetin response to 12-week quercetin supplementation in humans. Eur J Clin Nutr. 2010 Jul;64(7):692-7. doi: 10.1038/ejcn.2010.91. Epub 2010 Jun 2. — View Citation

Okamoto T. Safety of quercetin for clinical application (Review). Int J Mol Med. 2005 Aug;16(2):275-8. Review. — View Citation

Terao J, Murota K, Kawai Y. Conjugated quercetin glucuronides as bioactive metabolites and precursors of aglycone in vivo. Food Funct. 2011 Jan;2(1):11-7. doi: 10.1039/c0fo00106f. Epub 2010 Nov 17. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the plasma quercetin levels in COPD patients following supplementation with quercetin	Eligible COPD subjects will be supplemented with quercetin for one or four weeks and plasma quercetin levels will be measured prior to and after supplementation with quercetin or placebo. Safety of quercetin supplementation will also be determined based on blood and pulmonary function tests	One week in Phase I safety study and Four weeks in Phase II study	Yes
Secondary	Determine the effects of quercetin supplementation on the markers of oxidative stress in COPD subjects	Oxidative stress markers will be measured prior to and after quercetin or placebo supplementation; Protein carbonyls and nitrotyrosines; reduced glutathione; malondialdehyde.	4 weeks supplementation	Yes
Secondary	Determine the effects of quercetin supplementation on the markers of inflammation in COPD subjects	Sputum and blood levels of markers of inflammation will be measured prior to and after supplementation with placebo or quercetin; IL-6; IL-8; sICAM-1; CD40L; CC16; PARC/CCL18; surfactant D protein; C-reactive protein in blood only	4 Weeks supplementation	Yes