Do Laryngeal Tissue Changes in Patients Suspected of Having Laryngopharyngeal Reflux Predict Response to Treatment?

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00444145
Recruitment Status : Completed
First Posted : March 7, 2007
Results First Posted : March 29, 2017
Last Update Posted : March 29, 2017
Information provided by (Responsible Party):
Michael Vaezi, Vanderbilt University Medical Center

Brief Summary:

The purpose of the study is to determine if tissue changes are predictor of clinical response to therapy.

The hypothesis is that the patients who have laryngeal signs and symptoms related to acid reflux, will have ultrastructural changes on a laryngeal biopsy which are predictors of response to therapy.

Condition or disease Intervention/treatment Phase
Larynx Disease Gastroesophageal Reflux Drug: Prevacid Procedure: Esophageal and Laryngeal Biopsies Phase 4

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 24-hour 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 patient's 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 patient's 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. Our initial study which is also submitted for review will provide data on the prevalence of biopsy findings in controls, GERD and LPR patients. Subsequent to this prevalence study, the importance of these findings will be assessed based to determine if these findings will predict response to acid suppressive therapy.

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. The most important question which this protocol will address is if laryngeal findings specifically by either routine microscopy or electron microscopy would predict response to PPI therapy. This would then result in being able to identify GERD related laryngitis from non-GERD related causes.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Do Laryngeal Biopsy Findings Predict Treatment Response in Suspected Laryngopharyngeal Reflux
Actual Study Start Date : March 2007
Actual Primary Completion Date : March 2009
Actual Study Completion Date : December 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Biopsy GERD
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Patients with documented GERD or laryngopharyngeal reflux
Patients who have documented GERD as evidenced by erosive esophagitis or those patients who have newly diagnosed laryngopharyngeal reflux as diagnosed by endoscopy.
Drug: Prevacid
30 mg bid for 3 months
Other Name: lansoprazole
Procedure: Esophageal and Laryngeal Biopsies
repeat egd with biopsy after Prevacid 30 mg bid for 3 months
Other Name: esophagogastroduodenoscopy

Primary Outcome Measures :
  1. Number of Patients With Dilation of Intracellular Spaces 3 Months After Therapy [ Time Frame: 3 months ]
    Dilation of inter cellular spaces (the space within the cell) is reported to be an early morphological (structure and form) marker in gastro-oesophageal reflux. Using electron microscopy, the distance between epithelial cells is quantified.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:


  • Documented erosive esophagitis:

    • Patients will be newly diagnosed with esophageal erosion at initial visit via EGD
    • Patients with non-erosive esophagitis who have been responsive to PPI


  • Diagnosed via Head & Neck Institute endoscopists:

    • pts with chronic (> 3-months) history of hoarseness, throat clearing, sore- or burning throat and globus
    • Documentation of LPR using Larynx/Pharynx exam.

This group is commonly evaluated at the Vanderbilt Voice Center.

Exclusion Criteria:

  • Age < 18yrs
  • Pregnancy
  • Patients with contra-indications for EGD
  • Patients on corticosteroids
  • Active smokers
  • Patients with a history of regular (> 2 /day) alcohol use.
  • 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
  • Patients with known contraindication to lansoprazole.
  • Contraindications to biopsy: Taking anticoagulants other than aspirin (Coumadin, Plavix) or allergic to the local anesthetics.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00444145

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

Responsible Party: Michael Vaezi, Principal Investigator, Vanderbilt University Medical Center Identifier: NCT00444145     History of Changes
Other Study ID Numbers: 061244
First Posted: March 7, 2007    Key Record Dates
Results First Posted: March 29, 2017
Last Update Posted: March 29, 2017
Last Verified: February 2017

Additional relevant MeSH terms:
Gastroesophageal Reflux
Laryngopharyngeal Reflux
Laryngeal Diseases
Esophageal Motility Disorders
Deglutition Disorders
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Anti-Ulcer Agents
Gastrointestinal Agents
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action