Official Title: “Do Laryngeal Biopsy Findings Predict Treatment Response in Suspected Laryngopharyngeal Reflux”

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.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment

Study Primary Completion Date: January 2009

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.

Intervention(s) in this Clinical Trial

• Drug: Lansoprazole Tablet
  • 30 mg bid for 3 months
• Procedure: Esophageal and Laryngeal Biopsies
  • repeat egd with biopsy

Primary Measures

• Dilation of intracellular spaces 3 months after therapy
  • Time Frame: 3 months
    Safety Issue?: Yes

Inclusion Criteria:

GERD

• 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

LPR

• 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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Vanderbilt University

Overall Clinical Trial Officials and Contacts

Michael F Vaezi, MD PhD MS Principal Investigator Vanderbilt University  

Overall Contact: barbara mccafferty, RN 615-322-1897 barbara.mccafferty@vanderbilt.edu

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00444145

Study ID Number: 061244

ClinicalTrials.gov Identifier: NCT00444145

Health Authority: United States: Food and Drug Administration