Clinical trial NCT00444145: Do Laryngeal Tissue Changes in Patients Suspected of Having Laryngopharyngeal Reflux Predict Response to Treatment?
Official title: Do Laryngeal Biopsy Findings Predict Treatment Response in Suspected Laryngopharyngeal Reflux
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Larynx Disease
Gastroesophageal Reflux
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2007-03-07
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Patients With Dilation of Intracellular Spaces 3 Months After Therapy
timeFrame: 3 months
Secondary outcomes:
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center, Endoscopy Lab, TVC 1410
state: Tennessee
Study officials:
affiliation: Vanderbilt University
name: Michael F Vaezi, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: