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

This study has been completed.
Sponsor:
Information provided by:
Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00444145
First received: March 5, 2007
Last updated: November 12, 2010
Last verified: November 2010
  Purpose

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 Intervention Phase
Larynx Disease
Gastroesophageal Reflux
Drug: Lansoprazole Tablet
Procedure: Esophageal and Laryngeal Biopsies
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Do Laryngeal Biopsy Findings Predict Treatment Response in Suspected Laryngopharyngeal Reflux

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Dilation of intracellular spaces 3 months after therapy [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: March 2007
Study Completion Date: December 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Lansoprazole Tablet
    30 mg bid for 3 months
    Other Name: prevacid
    Procedure: Esophageal and Laryngeal Biopsies
    repeat egd 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 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00444145

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 Vanderbilt University
  More Information

No publications provided

Responsible Party: Michael F. Vaezi, MD, PhD, MS epi, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT00444145     History of Changes
Other Study ID Numbers: 061244
Study First Received: March 5, 2007
Last Updated: November 12, 2010
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
United States: Federal Government

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

ClinicalTrials.gov processed this record on November 20, 2014