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

NCT02226484 | Completed Phase 1

• 2 other identifiers: 13-05571R21DK097529-01A1
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Purpose:

1. 1.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
2. 2.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)

Conditions

Gastroesophageal Reflux Disease; GERD; Acid Reflux; Reflux

Keywords

Gastroesophageal reflux disease; GERD; Acid reflux; Reflux; Quercetin

Outcome Measures

Primary Outcomes (1)

• Expression of claudin-4 in esophageal squamous epithelium (ESE) of gastroesophageal reflux disease (GERD) in vivo

  To assess the change in claudin-4 levels in a given subject before and after administration of Quercetin (Q), our null hypothesis is that there will be no difference in claudin-4 levels (i.e. mean Δ of claudin-4 titer from t0 to t1 is 0) and the alternative hypothesis is that claudin-4 levels following the administration of Q will be significantly different than before administration. To test this hypothesis, we will perform paired Student's t-tests. If data violate normality, Wilcoxon signed-rank test will be used as a nonparametric alternative to the Student's t. Additionally, exploratory analysis will be performed to assess the impact of treatment on reflux scores, as demonstrated by changes in the GERD Symptom Assessment Scale (GSAS) before and after therapy.

  6 weeks

Secondary Outcomes (1)

• Barrier function and acid resistance of esophageal squamous epithelium (ESE) as measured by epithelial resistance, RT, and fluorescein flux.

  6 weeks

Study Arms (1)

Quercetin

EXPERIMENTAL

Two 250 mg capsules of oral quercetin (Q) twice-a-day (BID) one hour before meals with a glass of water for 6 weeks.

Drug: Quercetin

Interventions

Quercetin DRUG

Two 250 mg capsules of quercetin twice-a-day one hour before meals with a glass of water.

Quercetin

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

UNC Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

MeSH Terms

Conditions

Gastroesophageal Reflux

Interventions

Quercetin

Condition Hierarchy (Ancestors)

Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Nicholas Shaheen, MD, MPH

  UNC Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine and Epidemiology Chief, Division of Gastroenterology & Hepatology

Study Record Dates

• First Submitted: August 22, 2014
• First Posted: August 27, 2014
• Study Start: August 1, 2014
• Primary Completion: May 1, 2016
• Study Completion: June 1, 2016
• Last Updated: December 20, 2016

Record last verified: 2016-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)