Can Quercetin Increase Claudin-4 and Improve Esophageal Barrier Function in GERD?

University of North Carolina (UNC)

Status and phase

Completed

Phase 1

Conditions

Gastroesophageal Reflux Disease

Acid Reflux

GERD

Reflux

Treatments

Drug: Quercetin

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT02226484

1R21DK097529-01A1 (U.S. NIH Grant/Contract)

13-0557

Details and patient eligibility

About

Purpose:

Determine if oral quercetin increases the expression of claudin-4 in the lining of the esophagus of patients with a diagnosis of gastroesophageal reflux disease (GERD); and
Determine whether the increase in claudin-4 by oral quercetin is accompanied by improvement in the barrier function and acid resistance of the lining of the esophagus of patients with a diagnosis of gastroesophageal reflux disease (GERD)

If interested, participants will be consented and provided a questionnaire to complete as part of the study. Participants will undergo endoscopy for routine care and will have up to 8 esophageal biopsies (small tissue samples) taken for the research study. After endoscopy, participants will be contacted to begin a 6 week treatment period with study drug (Quercetin, taken twice daily).

At the end of the 6 week period, participants will be scheduled to have blood drawn and to have a follow-up endoscopy with biopsies performed for the research study.

Full description

Patients must be symptomatic (heartburn) and agree to allow endoscopic biopsies from the lower 5 cm of esophagus for research purposes. If the endoscopy demonstrates non-erosive reflux disease, biopsies of Esophageal Squamous Epithelium (ESE) are obtained and placed in mRNA-Later to assess claudin-4 mRNA by qRT-PCR and protein expression by Western blot (53, 64) while other biopsies of ESE are obtained and handled as in SpAim#2 to assess barrier function of ESE. After consent, subjects complete a questionnaire assessing demographics, disease-specific parameters such as duration of symptoms and past treatment, and the gastroesophageal reflux disease (GERD) Symptom Assessment Scale (GSAS), a validated measure of GERD severity. Following this, patients in open label fashion are given orally 500 mg Quercetin (Q) twice daily (bid) [Pure, House of Nutrition, Yonkers, NY] for 6-weeks. Symptoms are monitored 1 week before and for the 6 week treatment period. At 6 weeks, a blood sample is obtained for determination of Q and its metabolites by HPLC and endoscopy and biopsies of ESE are repeated and processed as initially done for claudin-4 levels in ESE.

Enrollment

26 patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

English speaking
Able to read, comprehend, and complete the consent form.
Aged 18 to 80
Diagnosed with gastroesophageal reflux disease (GERD) by a physician, defined as:

a. History of heartburn at > 3 times/week for > 4 months AND either: i. Abnormal 24hr-pH monitoring (acid contact time > 4.5% OR ii. Past responsiveness to proton pump inhibitor (PPI) therapy
Willing to undergo esophageal biopsy, endoscopy, and take study medication.
Willingness to discontinue or remain off PPIs for the duration of the study (rescue medication use during the study such as antacids and H2 blockers as needed for symptoms is permitted)

Exclusion criteria

Patients with a medical condition that makes him/her a poor risk for upper endoscopy, conscious sedation, esophageal biopsy or ability to comply with study directives
Current use of blood thinners such as coumadin, warfarin, heparin and/or low molecular weight heparin, and rivaroxaban (requires discontinuation of medication 5 days prior to and 6 days after EGD)
Patients with known bleeding disorders
Patients who are status post partial or complete esophageal resection
Patients with a history of esophageal or gastric surgery, includes fundoplication, gastric bypass, etc.
Patients with a history of esophageal varices, esophageal cancer, achalasia, Barrett's esophagus, or eosinophilic esophagitis,
Current diagnosis of invasive esophageal cancer
Current use of calcium channel blockers, estradiol, immune suppressive drugs, aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, and/or taxol/paclitaxel
Pregnant women
Patients with a history of being intolerant of Quercetin
Patients with continued moderate or severe heartburn despite use of twice daily PPIs (i.e. refractory to twice daily dosing of PPIs)
Patients with current active erosive esophagitis (assessed during baseline EGD).
Patients with a history of erosive esophagitis requiring PPI to treat. However, if patients have a history of erosive esophagitis and have discontinued PPI therapy at least 3 months prior to the baseline EGD, and there is no erosive disease seen during the baseline EGD, then these patients are eligible.
Patients with significant erosive gastropathy on baseline EGD requiring PPI to treat clinically.