Dexlansoprazole to Treat Laryngopharyngeal Reflux and Lingual Tonsil Hypertrophy
Recruitment status was Not yet recruiting
|First Received Date ICMJE||April 1, 2011|
|Last Updated Date||April 4, 2011|
|Start Date ICMJE||June 2011|
|Estimated Primary Completion Date||August 2012 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Lingual Tonsil Size [ Time Frame: 3 months ] [ Designated as safety issue: No ]
Lingual tonsil tissue size will be measured on computed tomography image at baseline and remeasured following CT imaging after 3 months of proton pump inhibitor therapy.
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT01328652 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Dexlansoprazole to Treat Laryngopharyngeal Reflux and Lingual Tonsil Hypertrophy|
|Official Title ICMJE||A Randomized, Double-blind, Placebo-controlled Study of Dexlansoprazole to Treat Laryngopharyngeal Reflux and Lingual Tonsil Hypertrophy|
Main Hypothesis: The investigators hypothesize that measurements of lingual tonsil tissue (LTT) thickness will decrease following treatment with once daily oral dexlansoprazole 60 mg in patients diagnosed with laryngopharyngeal reflux (LPR) and lingual tonsil hypertrophy (LTH) compared to matched controls receiving placebo.
Primary endpoints include:
Secondary endpoints include:
Specific Aims: The primary objective of this study is to determine whether treatment of patients diagnosed with LPR and LTH with 3 months of PPI therapy reduces LTT thickness, as measured on CT scan of the tongue base.
The secondary objectives of this study are to:
BACKGROUND AND SIGNIFICANCE:
Detail: The backflow of gastric contents into the esophagus occurs in healthy people to a limited extent. When the refluxed material transcends the upper esophageal sphincter and enters the laryngopharynx on a chronic basis, it is termed laryngopharyngeal reflux (LPR). LPR typically manifests as dysphonia, globus sensation, chronic cough, and throat irritation. Recent studies suggest that untreated LPR may be a cause of lingual tonsil hypertrophy (LTH), [2,3] which itself has been implicated as a contributing factor in obstructive sleep apnea-hypopnea syndrome (OSAHS).[4-6] Lingual tonsil tissue (LTT) is present to a variable degree in most individuals and tends to regress with age. Although standardized parameters for defining LTH have yet to be established, a recent study by Friedman et al  demonstrated that on average subjects with LPR, OSAHS, or both diseases had significantly thicker LTT on CT imaging than patients without either disease. Del Gaudio and coworkers  identified a trend between increasing severity of LTH and the frequency of reflux events, while Mamede et al  found a positive correlation between reflux symptoms and the degree of LTH.
LTH in the setting of LPR is thought to result from the edema and inflammation brought about by chronic exposure of the tissues to the refluxed acid. The resulting thickened and inflamed LTT may narrow the retrolingual airway, increasing the likelihood of airway obstruction and apneic events. Theoretically, increases in negative intrathoracic pressure secondary to the obstruction may, in turn, facilitate further LPR.
While the treatment of reflux has been shown to decrease indices of OSAHS severity in some patients, [8-10] a direct causal relationship between LPR and OSAHS has not been proven. Similarly, more evidence is necessary to elucidate the exact relationship between LPR and LTH. No study to date has investigated whether treatment of LPR reduces LTH. The investigators hypothesize that adequate treatment of LPR using a PPI in patients with LTH will result in a significant reduction in LTT thickness as well as improvement in OSAHS symptoms, if present. The proposed study is a randomized, double-blind, controlled trial to determine whether control of LPR reduces LTH and, as a corollary, improves OSAHS symptoms. Control of LPR will be determined by 24-hour oropharyngeal pH monitoring , and LTH will be measured on CT. While the length of time required for LTH regression to occur is not currently known, Reichel et al have found that 3 months of PPI therapy are typically necessary before improvement in LPR is seen.  Similarly, a study by Park et al showed a significantly greater rate of improvement or resolution of LPR symptoms when treatment with a PPI was for longer than 2 months.  PRELIMINARY STUDIES Preliminary Studies: In a previous study, the investigators utilized axial and sagittal CT images of the tongue base to measure LTT in patients with LPR, OSAHS, both conditions, or neither disease. The investigators found that patients with LPR, OSAHS, or LPR+OSAHS had significantly thicker LTT than patients without LPR or OSAHS. This study was presented at the 2009 Annual Meeting of the American Academy of Otolaryngology-Head and Neck Surgery and was published in the April 2010 issue of the journal Otolaryngology-Head and Neck Surgery.
RESEARCH DESIGN AND METHODS:
Overview: Prospective, randomized, double-blind, controlled study at a tertiary, university-affiliated medical center.
Sample size: In order to achieve a power of 0.95, a sample size of 40 subjects per group (80 total) was determined based on an a priori power analysis. The sample size stated in the original concept was an estimate and was not determined statistically.
Procedures: The study protocol begins after a patient has been diagnosed with laryngopharyngeal reflux (LPR) on the basis of routine history, physical exam, and diagnostic studies including 24-hour oropharyngeal pH monitoring with the Dx-pH Monitoring System (Restech, San Diego, California). Prospective candidates for the study will be asked to undergo CT imaging of the tongue base. Those who are subsequently diagnosed with lingual tonsil hypertrophy (LTH), as determined by mean lingual tonsil tissue (LTT) thickness greater than 3.0 mm on axial and sagittal views, will be eligible for enrollment, providing they meet the additional inclusion criteria listed above. The enrollment period is expected to last 12 months, and the total duration of the study is expected to be 18 months.
Once an eligible patient has agreed to participate in the study and provided informed consent, s/he will be randomly assigned to the experimental or control group according to a 1:1 ratio. Patients as well as the practitioner administering treatment will be blinded to patient group assignments. Patients in the experimental group will be started on a 3-month regimen of once daily oral dexlansoprazole 60 mg. Patients in the control group will receive a placebo once daily by mouth for the same length of time. Following completion of the 3-month treatment regimen, patients from both groups will undergo repeat 24-hour oropharyngeal pH testing and CT of the tongue base. Endoscopic findings of LPR will also be recorded before, monthly during treatment and after treatment using the Reflux Finding Score (RFS). A 3-month treatment period was chosen based on previous studies, which have shown failure of symptom resolution after shorter lengths of time. Once enrolled, patients will be seen in clinic approximately every four weeks. Treatment with cimetidine 200 mg PO BID will be offered as a rescue medication to patients of either group whose LPR symptoms worsen during the study. Once started, cimetidine, as well as study drug (dexlansoprazole or placebo) will be continued for the duration of the study. At study conclusion, all patients will be re-evaluated for continued treatment, based on the effectiveness of dexlansoprazole (after unblinding) and need for rescue medication (dexlansoprazole and placebo). If cimetidine fails to offer relief, the subject will be withdrawn from the study and other treatment options will be offered.
The Calgary Sleep Apnea Quality of Life Index (CSAQLI), visual analog scale for snoring (VAS), and Epworth Sleepiness Scale (ESS) will be used as subjective outcome metrics. These questionnaires are validated tools for assessing symptoms of obstructive sleep apnea/hypopnea syndrome (OSAHS) and associated quality of life. The Reflux Symptom Index (RSI), a validated instrument for assessing reflux symptoms, will also be administered along with the other questionnaires both prior to initiating therapy and again at the end of the 3-month period.
Data analysis and Interpretation:
Statistical analysis will focus on determining whether lingual tonsil tissue size differs before and after therapy. Mean lingual tonsil tissue size will be calculated along with standard deviation and student t test will be used to determine statistical significance.
Analysis will also examine the mean change in four subjective metrics, (1) Calgary Sleep Apnea Quality of Life Index, (2) Visual Analog Scale of snoring, (3) Epworth Sleepiness scale, and (4) Reflux Symptom Index. Again, means and standard deviations will be calculated and student t test will be used to assess statistical significance.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 4|
|Study Design ICMJE||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Intervention ICMJE||Drug: dexlansoprazole
dexlansoprazole 60 mg once daily for 3 months
|Study Arm (s)||Experimental: Proton Pump Inhibitor
Treatment with dexlansoprazole 60 mg once daily for 3 months
Intervention: Drug: dexlansoprazole
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Not yet recruiting|
|Estimated Enrollment ICMJE||80|
|Estimated Completion Date||January 2013|
|Estimated Primary Completion Date||August 2012 (final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||18 Years to 59 Years|
|Accepts Healthy Volunteers||No|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT01328652|
|Other Study ID Numbers ICMJE||004 10/10|
|Has Data Monitoring Committee||No|
|Responsible Party||Michael Friedman, MD, Head and Neck and Cosmetic Surgery, Inc.and Advanced Center for Specialty Care|
|Study Sponsor ICMJE||Advanced Center for Specialty Care|
|Information Provided By||Advanced Center for Specialty Care|
|Verification Date||April 2011|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP