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

October 31, 2016 updated by: Umadevi S. Sajjan, University of Michigan

Phase I Study to Determine the Safety of Quercetin in COPD Patients

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Sugar chew-Cohort 1
contains 350 mg of vitamin C and 10 mg niacin
Other: Placebo - sugar chew
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)
Active Comparator: Quercetin 1-Cohort 1
Quercetin chew containing 500 mg quercetin, 350 mg vitamin C and 10 mg niacin
Drug: Quercetin

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
Other Names:
  • QB3C without folic acid
Active Comparator: Quercetin 2-Cohort 2
Quercetin chew containing 1000 mg quercetin, 350 mg vitamin C and 10 mg niacin
Drug: Quercetin

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
Other Names:
  • QB3C without folic acid
Active Comparator: Quercetin 3-Cohort 3
Quercetin chew containing 2000 mg quercetin, 350 mg vitamin C and 10 mg niacin
Drug: Quercetin

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
Other Names:
  • QB3C without folic acid
Placebo Comparator: Sugar chew-Cohort 2
contains 350 mg of vitamin C and 10 mg niacin
Other: Placebo - sugar chew
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)
Placebo Comparator: Sugar Chew-Cohort 3
contains 350 mg of vitamin C and 10 mg niacin
Other: Placebo - sugar chew
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: One week in Phase I safety study

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Michigan

Collaborators

National Institutes of Health (NIH)
National Center for Complementary and Integrative Health (NCCIH)
Quercegen Pharmaceuticals

Investigators

  • Principal Investigator: Fernando J Martinez, M.D., University of Michigan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2014

Primary Completion (Actual)

October 1, 2015

Study Completion (Actual)

October 1, 2015

Study Registration Dates

First Submitted

October 10, 2012

First Submitted That Met QC Criteria

October 15, 2012

First Posted (Estimate)

October 16, 2012

Study Record Updates

Last Update Posted (Estimate)

December 26, 2016

Last Update Submitted That Met QC Criteria

October 31, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HUM00061735
  • R21AT007357 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Chronic Obstructive Pulmonary Disease

Clinical Trials on Placebo - sugar chew

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Angola

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe