Esophageal and Laryngeal Tissue Changes in Patients Suspected of Having Laryngopharyngeal Reflux (biopsy I)

This study has been completed.
Sponsor:
Information provided by:
Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00373997
First received: September 5, 2006
Last updated: March 15, 2011
Last verified: March 2011
  Purpose

The purpose of the study is to determine whether patients with suspected Laryngopharyngeal reflux have inflammation and ultrastructural injury on their laryngeal biopsies.


Condition Intervention Phase
Larynx Disease
Gastroesophageal Reflux
Procedure: Esophageal and Laryngeal biopsies
Procedure: egd with biopsy
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Role of Esophageal and Laryngeal Biopsies in Suspected Laryngopharyngeal Reflux

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Dilation of intracellular spaces at the beginning of the study [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 45
Study Start Date: September 2006
Study Completion Date: December 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Procedure: Esophageal and Laryngeal biopsies
    one day procedure
    Other Name: esophagogastroduodenoscopy
    Procedure: egd with biopsy
    standard of care procedure with biopsy
    Other Name: esophagogastroduodenoscopy
Detailed Description:

Gastroesophageal reflux disease (GERD) has been implicated, in part, as the cause of various laryngeal signs and symptoms (1-7). This is often termed reflux laryngitis, ear, nose, and throat (ENT) reflux, or laryngopharyngeal reflux (LPR). GERD was first described to be a causative agent in developing contact ulcers of the larynx (8), and since this early report other routinely observed laryngeal signs are now attributed to LPR. These include laryngeal edema/erythema, vocal cord granulomas and polyps, posterior cricoid cobblestoning, interarytenoid changes, and subglottic stenosis. In addition, patient symptoms attributed to LPR include hoarseness, sore or burning throat, chronic cough, throat clearing, globus, nocturnal laryngospasm, otalgia, post-nasal drip, and dysphagia.

GERD occurs in 7% - 25% of the population on a daily or monthly basis, respectively (9). It is estimated that up to 10% of patients presenting to ENT physicians do so because of complaints that are thought to be related to LPR (2).

The current management of patients with suspected LPR complaints include either 1. empiric therapy using proton pump inhibitors (PPI's) or 2. Ambulatory 24hour pH monitoring to test for GERD before beginning treatment. Because of the uncertainty and subjectivity of the ENT laryngeal examination in diagnosing LPR, both algorithms fall short of ideal in treating these patients. In a recent review of the literature, remarkably, up to 50% of patients with laryngoscopic signs suggesting LPR do not respond to aggressive acid suppression and do not have abnormal esophageal acid reflux values on pH testing (10). Yet, in this subset of patients LPR continues to be implicated as the probable etiology of the patients laryngeal signs and symptoms.

Calabrese, et al. recently looked at the reversibility of GERD related ultrastructural alterations in the esophagus using a PPI. Lower esophageal biopsies were analyzed with electron microscopy (EM) for ultrastructural alterations attributed to GERD; that is, dilation of intracellular spaces. Patients were then treated with a PPI and re-biopsied for analysis of any changes of healing that may have occurred in these ultrastructural alterations. Not surprisingly, the ultrastructural alterations showed complete recovery (reduction of dilated intracellular spaces) after treatment with a PPI. Additionally resolution of patients symptoms coincided with recovery of ultrastructural alterations (11). No such biopsies looking for LPR related changes in the larynx have ever been performed in human subjects.

In sum, LPR is an extremely subjective diagnosis, in which nearly half of all patients do not have an abnormal 24hr pH study, nor do they respond to the standard GERD therapy of acid suppression. Finding an alternative objective criterion for GERD induced laryngitis would be an important clinical discovery. To date, there are no data on microscopic changes in the larynx of patients suspected of having LPR.

In sum, LPR is an extremely subjective diagnosis, in which nearly half of all patients do not have an abnormal 24hr pH study, nor do they respond to the standard GERD therapy of acid suppression. To date, there is no microscopic evidence of laryngeal damage caused by LPR.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • GERD 1. Documented erosive esophagitis (Patients will be newly diagnosed with esophageal erosion at initial visit via esophagogastroduodenoscopy [EGD]) 2.Patients with non-erosive esophagitis who have been responsive to PPI
  • LPR 1. Diagnosed via Head & Neck Institute endoscopists (i.e. patients will be newly diagnosed at initial visit via laryngoscopy)
  • Controls

    1. No complaints or history of heartburn, acid regurgitation, atypical chest pain
    2. Never been seen by GI or ENT for related symptoms
    3. No prior therapy for GERD
    4. Have a medical condition other than reflux for which they need to undergo EGD. These conditions can be diarrhea, peptic ulcer disease, malabsorption, anemia, and dysphagia.

Exclusion Criteria

  • Age < 18yrs
  • Pregnancy
  • Patients with contra-indications for EGD
  • Use of antacid (PPI, H2RB) within last 30 days
  • Use of any/all medications affecting gastrointestinal motility
  • Known history of: Barrett's esophagus, Peptic stricture, Pyloric stenosis, Gastric resection
  • Patients unable to give informed consent
  • Patients unable to comply with follow-up
  • Contraindications to biopsy: Taking anticoagulants other than aspirin (Coumadin, Plavix) or allergies to local anesthetic.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00373997

Locations
United States, Tennessee
Vanderbilt University Medical Center, Endoscopy Lab, TVC 1410
Nashville, Tennessee, United States, 37232-5280
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Michael F Vaezi, MD, PhD, MS epi Vanderbilt University
  More Information

No publications provided

Responsible Party: Michael Vaezi, MD, PhD, MS epi, Vanderbilt University Meidcal Center
ClinicalTrials.gov Identifier: NCT00373997     History of Changes
Other Study ID Numbers: 060725
Study First Received: September 5, 2006
Last Updated: March 15, 2011
Health Authority: United States: Institutional Review Board
United States: Federal Government

Additional relevant MeSH terms:
Gastroesophageal Reflux
Laryngeal Diseases
Regurgitation, Gastric
Esophageal Motility Disorders
Deglutition Disorders
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Respiratory Tract Diseases
Otorhinolaryngologic Diseases

ClinicalTrials.gov processed this record on April 23, 2014