Clinical trial NCT02226484: Can Quercetin Increase Claudin-4 and Improve Esophageal Barrier Function in GERD?
Official title: Can Quercetin Increase Claudin-4 and Improve Esophageal Barrier Function in GERD?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gastroesophageal Reflux Disease
GERD
Acid Reflux
Reflux
Keywords: Gastroesophageal reflux disease
GERD
Acid reflux
Reflux
Quercetin
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2014-08-27
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Purpose:

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. 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Expression of claudin-4 in esophageal squamous epithelium (ESE) of gastroesophageal reflux disease (GERD) in vivo
timeFrame: 6 weeks
Secondary outcomes:
measure: Barrier function and acid resistance of esophageal squamous epithelium (ESE) as measured by epithelial resistance, RT, and fluorescein flux.
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: UNC Chapel Hill
state: North Carolina
Study officials:
affiliation: UNC Chapel Hill
name: Nicholas Shaheen, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: