Ignite Creation Date:
2024-05-05 @ 11:24 PM
Last Modification Date:
2024-10-26 @ 10:33 AM
Study NCT ID:
NCT01328652
Status:
UNKNOWN
Last Update Posted:
2011-04-05
First Post:
2011-04-01
Brief Title:
Dexlansoprazole to Treat Laryngopharyngeal Reflux and Lingual Tonsil Hypertrophy
Sponsor:
Advanced Center for Specialty Care
Organization:
Advanced Center for Specialty Care
Study Overview
Official Title:
A Randomized Double-blind Placebo-controlled Study of Dexlansoprazole to Treat Laryngopharyngeal Reflux and Lingual Tonsil Hypertrophy
Status:
UNKNOWN
Status Verified Date:
2011-04
Last Known Status:
NOT_YET_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
24-hour oropharyngeal pH testing pre- and post-treatment
Mean lingual tonsil tissue LTT thickness pre- and post-treatment as determined by CT scan of the base of tongue
Secondary endpoints include
Reflux Finding Score RFS on pre- and post-treatment endoscopy of the oropharynx
Subjective outcome metrics for assessing LPR-related symptoms and associated quality of life
Calgary Sleep Apnea Quality of Life Index
Bed-partner assessment of snoring intensity according to a Visual Analog Scale
Epworth Sleepiness Scale ESS
Reflux Symptom Index RSI
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
Evaluate changes in LPR-related symptoms and quality of life after therapy using the following subjective outcome metrics
Calgary Sleep Apnea Quality of Life Index
Bed-partner assessment of snoring intensity according to a Visual Analog Scale
Epworth Sleepiness Scale
Reflux symptom index
Correlate changes in LTT thickness with the following secondary endpoints
Changes in the above subjective outcome metrics
Changes in endoscopic findings of LPR
Changes in 24-hour oropharyngeal pH study results
Primary endpoints include
24-hour oropharyngeal pH testing pre- and post-treatment
Mean lingual tonsil tissue LTT thickness pre- and post-treatment as determined by CT scan of the base of tongue
Secondary endpoints include
Reflux Finding Score RFS on pre- and post-treatment endoscopy of the oropharynx
Subjective outcome metrics for assessing LPR-related symptoms and associated quality of life
Calgary Sleep Apnea Quality of Life Index
Bed-partner assessment of snoring intensity according to a Visual Analog Scale
Epworth Sleepiness Scale ESS
Reflux Symptom Index RSI
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
Evaluate changes in LPR-related symptoms and quality of life after therapy using the following subjective outcome metrics
Calgary Sleep Apnea Quality of Life Index
Bed-partner assessment of snoring intensity according to a Visual Analog Scale
Epworth Sleepiness Scale
Reflux symptom index
Correlate changes in LTT thickness with the following secondary endpoints
Changes in the above subjective outcome metrics
Changes in endoscopic findings of LPR
Changes in 24-hour oropharyngeal pH study results
Detailed Description:
BACKGROUND AND SIGNIFICANCE
Detail The backflow of gastric contents into the esophagus occurs in healthy people to a limited extent1 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 23 which itself has been implicated as a contributing factor in obstructive sleep apnea-hypopnea syndrome OSAHS4-6 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 7 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 2 identified a trend between increasing severity of LTH and the frequency of reflux events while Mamede et al 3 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 11 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 12 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 13 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 LPROSAHS 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 095 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 30 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 she will be randomly assigned to the experimental or control group according to a 11 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 apneahypopnea 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
Detail The backflow of gastric contents into the esophagus occurs in healthy people to a limited extent1 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 23 which itself has been implicated as a contributing factor in obstructive sleep apnea-hypopnea syndrome OSAHS4-6 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 7 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 2 identified a trend between increasing severity of LTH and the frequency of reflux events while Mamede et al 3 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 11 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 12 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 13 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 LPROSAHS 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 095 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 30 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 she will be randomly assigned to the experimental or control group according to a 11 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 apneahypopnea 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None