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

NCT01708278 | Completed Phase 1 Results DMC

• 2 other identifiers: HUM00061735R21AT007357
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

COPD; Emphysema; chronic bronchitis; Quercetin; flavonoids

Outcome Measures

Primary Outcomes (1)

• Participants Who Experienced Safety Concerns, Where Safety Concerns of Quercetin Supplementation is Indicated by Significant Change From Baseline Measures of Tests Indicated Below in Outcome Measure Description

  Note: If values for any of the measures indicated here were found, the participant would be indicated as a participant with a safety concern, and values for that particular measure would be posted specifically, but since none of the participants experienced these outlying values, results of all tests are expressed here as a composite function. PULMONARY FUNCTION TEST: FEV1% of predicted: decline by \>20% from baseline COMPLETE BLOOD COUNTS: WBC (cells)/mm3 : \<2000, Platelets (cells)/mm3: \<25,000, Hemoglobin (g/dL): \<7.0 COMPREHENSIVE METABOLIC PROFILE (study drug related):Sodium (mmol/L): \<125 or \>148, Potassium (mmol/L): \< 3.0 or \> 6.0, Calcium (mmol/L): \<7.4 or \> 11.5, LIVER FUNCTION TESTS INCREASE BY FACTOR: Enzymes ALT, AST, and Alkaline phosphate, Total bilirubin: for any of these a value \>3X upper limit of normal

  One week in Phase I safety study

Study Arms (6)

Sugar chew-Cohort 1

PLACEBO COMPARATOR

contains 350 mg of vitamin C and 10 mg niacin

Other: Placebo - sugar chew

Quercetin 1-Cohort 1

ACTIVE COMPARATOR

Quercetin chew containing 500 mg quercetin, 350 mg vitamin C and 10 mg niacin

Drug: Quercetin

Quercetin 2-Cohort 2

ACTIVE COMPARATOR

Quercetin chew containing 1000 mg quercetin, 350 mg vitamin C and 10 mg niacin

Drug: Quercetin

Quercetin 3-Cohort 3

ACTIVE COMPARATOR

Quercetin chew containing 2000 mg quercetin, 350 mg vitamin C and 10 mg niacin

Drug: Quercetin

Sugar chew-Cohort 2

PLACEBO COMPARATOR

contains 350 mg of vitamin C and 10 mg niacin

Other: Placebo - sugar chew

Sugar Chew-Cohort 3

PLACEBO COMPARATOR

contains 350 mg of vitamin C and 10 mg niacin

Other: Placebo - sugar chew

Interventions

Quercetin DRUG

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 1. Quercetin 500 mg/350 mg of vitamin C and 10 mg niacin 2. Quercetin 1000 mg/350 mg of vitamin C and 10 mg niacin 3. Quercetin 2000 mg/350 mg of vitamin C and 10 mg niacin

Also known as: QB3C without folic acid

Quercetin 1-Cohort 1; Quercetin 2-Cohort 2; Quercetin 3-Cohort 3

Placebo - sugar chew OTHER

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)

Sugar Chew-Cohort 3; Sugar chew-Cohort 1; Sugar chew-Cohort 2

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Michigan: lead
• National Institutes of Health (NIH): collaborator
• Quercegen Pharmaceuticals: collaborator
• National Center for Complementary and Integrative Health (NCCIH): collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (11)

• 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(1):131. doi: 10.1186/1465-9921-11-131.

  PMID: 20920189 BACKGROUND

• 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.

  PMID: 22465313 BACKGROUND

• 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.

  PMID: 21507984 BACKGROUND

• 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.

  PMID: 20517329 BACKGROUND

• 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.

  PMID: 18549926 BACKGROUND

• 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.

  PMID: 21773581 BACKGROUND

• 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.

  PMID: 21324570 BACKGROUND

• 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.

  PMID: 18827577 BACKGROUND

• 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. doi: 10.1016/j.fct.2007.05.015. Epub 2007 Jun 7.

  PMID: 17698276 BACKGROUND

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

  PMID: 16012761 BACKGROUND

• Han MK, Barreto TA, Martinez FJ, Comstock AT, Sajjan US. Randomised clinical trial to determine the safety of quercetin supplementation in patients with chronic obstructive pulmonary disease. BMJ Open Respir Res. 2020 Feb;7(1):e000392. doi: 10.1136/bmjresp-2018-000392.

  PMID: 32071149 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Emphysema; Bronchitis, Chronic

Interventions

Quercetin; Folic Acid

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bronchitis; Respiratory Tract Infections; Infections; Bronchial Diseases

Intervention Hierarchy (Ancestors)

Flavonols; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pterins; Pteridines

Results Point of Contact

• Title: Fernando Martinez
• Organization: University of Michigan

fmartine@umich.edu

(734) 763-2540

Study Officials

• Fernando J Martinez, M.D.

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 10, 2012
• First Posted: October 16, 2012
• Study Start: February 1, 2014
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: December 26, 2016
• Results First Posted: December 26, 2016

Record last verified: 2016-10

Locations

US (1)