Do Laryngeal Tissue Changes in Patients Suspected of Having Laryngopharyngeal Reflux Predict Response to Treatment?
|ClinicalTrials.gov Identifier: NCT00444145|
Recruitment Status : Completed
First Posted : March 7, 2007
Results First Posted : March 29, 2017
Last Update Posted : March 29, 2017
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|
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)|
|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|
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.
30 mg bid for 3 months
Other Name: lansoprazoleProcedure: Esophageal and Laryngeal Biopsies
repeat egd with biopsy after Prevacid 30 mg bid for 3 months
Other Name: esophagogastroduodenoscopy
- 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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00444145
|United States, Tennessee|
|Vanderbilt University Medical Center, Endoscopy Lab, TVC 1410|
|Nashville, Tennessee, United States, 37232-5280|
|Principal Investigator:||Michael F Vaezi, MD,PhD||Vanderbilt University|