Clinical trial NCT06003270: Biological Effects of Quercetin in COPD Phase II
Official title: Effects of Quercetin on the Oxidative Stress and Inflammatory Markers in COPD Phase II
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic Obstructive Pulmonary Disease
Emphysema
Chronic Bronchitis With Airway Obstruction
Keywords: COPD, quercetin, polyphenol, mucus, airway obstruction
Lead sponsor: Temple University
Sponsor class: OTHER
Collaborators: name: National Center for Complementary and Integrative Health (NCCIH)
name: Quercegen Pharmaceuticals
First posted: 2023-08-21
Enrollment: 30
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double blinded placebo controlled study
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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
* 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

Primary outcomes:
measure: C-reactive protein (CRP), and surfactant protein (SP)-D in serum
timeFrame: six months
measure: Club cell protein 16 (CC16) pg/ml
timeFrame: six months
Secondary outcomes:
measure: Quercetin
timeFrame: six months
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Nathaniel Marchetti
state: Pennsylvania
Study officials:
affiliation: Temple University
name: Nathaniel Marchetti
role: PRINCIPAL_INVESTIGATOR
References:
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(1):131. doi: 10.1186/1465-9921-11-131.
citation: Farazuddin M, Mishra R, Jing Y, Srivastava V, Comstock AT, Sajjan US. Quercetin prevents rhinovirus-induced progression of lung disease in mice with COPD phenotype. PLoS One. 2018 Jul 5;13(7):e0199612. doi: 10.1371/journal.pone.0199612. eCollection 2018.
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.
citation: 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.