Ignite Creation Date:
2024-05-05 @ 6:56 PM
Last Modification Date:
2024-10-26 @ 9:39 AM
Study NCT ID:
NCT00576498
Status:
COMPLETED
Last Update Posted:
2012-10-29
First Post:
2007-12-18
Brief Title:
Novel Imaging Techniques in Barretts Esophagus
Sponsor:
Midwest Biomedical Research Foundation
Organization:
Midwest Veterans Biomedical Research Foundation
Study Overview
Official Title:
Detection Of Intestinal Metaplasia And High Grade Dysplasia In Barretts Esophagus Using Novel Imaging Techniques - A Randomized Controlled Trial
Status:
COMPLETED
Status Verified Date:
2012-10
Last Known Status:
None
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:
Primary Aim In patients with endoscopically suspected BE compared to standard endoscopy novel techniques NBI and AFI with target biopsies will
Detect more patients with intestinal metaplasia
Detect more areas of high grade dysplasia
Require fewer biopsies and a shorter time for procedure completion
Secondary Aim
Compare the yield of high-grade dysplasiaHGDusing NBIAFI versus standard endoscopy with biopsy
Compare the number of biopsies and procedure times for NBIAFI versus standard endoscopy with biopsy
Compare the inter-observer variability in classifying different mucosal and vascular patterns observed by NBIAFI using kappa statistics
Detect more patients with intestinal metaplasia
Detect more areas of high grade dysplasia
Require fewer biopsies and a shorter time for procedure completion
Secondary Aim
Compare the yield of high-grade dysplasiaHGDusing NBIAFI versus standard endoscopy with biopsy
Compare the number of biopsies and procedure times for NBIAFI versus standard endoscopy with biopsy
Compare the inter-observer variability in classifying different mucosal and vascular patterns observed by NBIAFI using kappa statistics
Detailed Description:
Barretts esophagus BE is the pre-malignant lesion for adenocarcinoma of the esophagus and esophagogastric junction It is a condition in which the squamous mucosa of the distal esophagus is replaced by columnar mucosa specifically intestinal metaplasia The incidence of esophageal adenocarcinoma has been rapidly rising and has increased 3-6 fold over the past two decades This has driven efforts to identify patients with the pre-malignant lesion ie BE Intestinal metaplasia within the columnar lined esophagus is the epithelial type that predisposes patients to the development of adenocarcinoma the other two epithelial types being cardiac and fundic
Since intestinal metaplasia is now included in the definition and is the epithelial type associated with cancer obtaining biopsies from the columnar lined distal esophagus is mandatory The sensitivity and the positive predictive value of standard EGD for diagnosing BE has been reported as 82 and 34 respectively This is secondary to the patchy and mosaic presence of intestinal metaplasia in the columnar distal esophagus Endoscopic screening is advocated in patients with chronic GERD symptoms for detection of BE with random biopsies being obtained if a columnar appearing distal esophagus is visualized Once intestinal metaplasia is detected with these random biopsies and the diagnosis of BE is confirmed patients are subsequently enrolled in a surveillance program Similarly the presence of dysplasia or early adenocarcinoma within a segment of BE is patchy and focal and standard endoscopy and random biopsies may fail to detect these lesions New endoscopic imaging techniques to improve the accuracy of endoscopic diagnosis have recently been developed and most are currently under evaluation
METHODS Study OverviewPatient presenting to GI lab for BE screening and surveillance Informed consent signed and patient randomized if endoscopic BE is suspected to NBI target biopsies or standard endoscopy with biopsies as the first procedure If randomized to NBI first patterns noted target biopsies obtained from specific patterns Same patient returns in 3-6 weeks for 2nd procedure Standard endoscopy 4 quadrant every 2 cms random biopsies ie standard BE surveillance Findings of NBI and random biopsies compared after all patients complete protocol and results analyzed A process similar to the one outlined above will be used in comparing autofluorescence imaging to conventional endoscopy in patients with Barretts mucosa
Study DesignThis study is part of a multicenter randomized controlled trial being conducted at two sites the other one being Medical University of South Carolina Patients will be randomized opaque sealed envelopes generated by statistician to undergo NBIAFI or standard endoscopy with biopsies on day 1 The same patient will return for the alternative procedure with biopsies within 3-6 weeks of the 1st procedure and will be maintained on acid suppressive therapy during this time interval Each patient will thus act as hisher own control At the time of performing the 2nd procedure either NBIAFI target biopsies or standard endoscopy the endoscopist will be blinded and will not be aware of the biopsy results from the 1st procedure Every attempt will also be made to keep the endoscopists blinded to the past history of the patient ie non dysplastic BE LGD HGD etc
Risk and benefit to the study participantData on newer imaging method like NBI and AFI are mostly in the form of case series This has not led to a change in the standard of care The early data is very encouraging but not conclusive due to lack of randomized controlled trials Hence we chose a study design of randomized controlled trial of the newer modalities versus the existing conventional endoscopy This design necessitates the performance of a repeat endoscopy Upper endoscopy is very safe routinely done procedure with a low risk of complications A repeat procedure may indeed increase the potential for risks associated with the procedure but the magnitude is small The added advantage of second endoscopy would be increased detection of dysplasia and adenocarcinoma resulting in potential benefit to the patients The main reason for the performance of the current study is the limitation of conventional endoscopy with the implication that dysplasia and adenocarcinoma will be missed on the initial endoscopy In clinical practice this usually warrants a follow up endoscopy that is performed at 1-3 yr intervals due to time and cost constraints For the study population of this trial the second endoscopy has the potential for increased detection of dysplasiaearly adenocarcinoma in the Barretts segment that could lead to initiation of curative therapy
Study PopulationPatients undergoing BE screening and surveillance will be enrolled after written informed consent BE definition- columnar mucosa in the distal esophagus of any length with intestinal metaplasia on biopsy The BE length will be measured from the gastroesophageal junction to the proximally displaced squamo-columnar junction The patient demographics age gender and ethnicity and the BE length will be recorded Total time required for each procedure will be recorded - from endoscope insertion to removal
Narrow Band Imaging Patients will be evaluated with a standard magnification endoscope Olympus GIF Q240Z 115x or GIF-H180 or equivalent using a NBI light source already available at both centers The outer diameter of the endoscope is 108 mm similar to standard diagnostic endoscopes No special processing or cleaning of the endoscope is required - similar to the standard Olympus GIF-100 A cap may or may not be fitted on the distal tip of the endoscope allowing the mucosa in contact with the cap to be magnified without the motility of the esophagus affecting visualization The different patterns will be grouped into ridgevillous circular and irregulardistorted Target biopsies with standard biopsy forceps will be obtained from the different visualized patterns in separate jars
Autofluorescence Imaging Patients will be evaluated using a prototype autofluorescence endoscope Olympus Tokyo Japan excitation 395-475 nm fluorescence detection 490-625 nm red reflectance 600-620 nm and green reflectance 540-560 nm The AFI scope has two different CCD charge coupled device to detect the light waves emittedreflected from the biological tissue - similar to the chip used in a digital camera one for conventional and another for AFI endoscopy There is also a rotary filter that allows blue red or green light to be generated selectively The video processor constructs video images AFI images or normal optical images based on the signals provided by CCD at the distal end of the endoscope In this system normal squamous and non-dysplastic BE appears green while the dysplastic areas appear magentapurplish Targeted biopsies will be obtained from the areas with abnormal fluorescence Both the NBI and AFI equipment will be supplied by Olympus America Inc
Standard Endoscopy Patients will undergo EGD with biopsies using a standard diagnostic video endoscope Olympus GIF 140 or 160 using the Seattle protocol - 4 quadrant biopsies using standard biopsy forceps every 2 cms stored in separate jars
Histology All biopsy specimens will be stained with HE and alcian blue at pH 25 will then be reviewed by two pathologists SM and DL one at each site who will be blinded to the NBIAF results and patterns Any disagreement in the histological diagnosis will be resolved by a consensus diagnosis Dysplasia will be classified as no dysplasia LGD HGD and adenocarcinoma
Data CollectionPatient demographics order of randomization endoscopy findings BE length NBI patterns AFI patterns procedure time number of biopsies and histology reports will be collected and recorded by the study coordinator All this information will be transferred into an ACCESS database
Statistical Power Data AnalysisFor the primary outcome to determine if NBIAFI target biopsies can diagnose BE intestinal metaplasia in 90 of the patients assuming that standard endoscopy with biopsy can diagnose Barretts in 70 we would need 122 patients in order to detect a significant difference between the two with 80 power and a type I error rate of 5 using McNemars test for paired dichotomous responses
For the secondary outcome of detection of HGD will be based on number of biopsies harboring HGD If we assume that NBIAFI can detect areas of HGD within the BE segment in 90 of the biopsies from irregulardistorted patterns compared to 60 by standard endoscopy we would need to study 59 areasbiopsies of HGD in order to detect a significant difference between the two with 80 power and a type 1 error rate of 5 using McNemars test for paired dichotomous responses If we enroll at least 10-12 patients with HGD with an average BE length of 5 cms we will be able to evaluate 60 areas of HGD with each procedure Each site will have to enroll approximately 30-35 BE patients including 5-6 with HGD each year
McNemars test will be used to compare paired categorical data while continuous paired data will be compared using non-parametric methods such as the Wilcoxon Sign Rank Test A p value of 005 will be considered significant
For the initial 30 consecutive patients enrolled in the study inter-observer variability will be studied on the mucosal and vascular patterns and autofluorescence patterns
Since intestinal metaplasia is now included in the definition and is the epithelial type associated with cancer obtaining biopsies from the columnar lined distal esophagus is mandatory The sensitivity and the positive predictive value of standard EGD for diagnosing BE has been reported as 82 and 34 respectively This is secondary to the patchy and mosaic presence of intestinal metaplasia in the columnar distal esophagus Endoscopic screening is advocated in patients with chronic GERD symptoms for detection of BE with random biopsies being obtained if a columnar appearing distal esophagus is visualized Once intestinal metaplasia is detected with these random biopsies and the diagnosis of BE is confirmed patients are subsequently enrolled in a surveillance program Similarly the presence of dysplasia or early adenocarcinoma within a segment of BE is patchy and focal and standard endoscopy and random biopsies may fail to detect these lesions New endoscopic imaging techniques to improve the accuracy of endoscopic diagnosis have recently been developed and most are currently under evaluation
METHODS Study OverviewPatient presenting to GI lab for BE screening and surveillance Informed consent signed and patient randomized if endoscopic BE is suspected to NBI target biopsies or standard endoscopy with biopsies as the first procedure If randomized to NBI first patterns noted target biopsies obtained from specific patterns Same patient returns in 3-6 weeks for 2nd procedure Standard endoscopy 4 quadrant every 2 cms random biopsies ie standard BE surveillance Findings of NBI and random biopsies compared after all patients complete protocol and results analyzed A process similar to the one outlined above will be used in comparing autofluorescence imaging to conventional endoscopy in patients with Barretts mucosa
Study DesignThis study is part of a multicenter randomized controlled trial being conducted at two sites the other one being Medical University of South Carolina Patients will be randomized opaque sealed envelopes generated by statistician to undergo NBIAFI or standard endoscopy with biopsies on day 1 The same patient will return for the alternative procedure with biopsies within 3-6 weeks of the 1st procedure and will be maintained on acid suppressive therapy during this time interval Each patient will thus act as hisher own control At the time of performing the 2nd procedure either NBIAFI target biopsies or standard endoscopy the endoscopist will be blinded and will not be aware of the biopsy results from the 1st procedure Every attempt will also be made to keep the endoscopists blinded to the past history of the patient ie non dysplastic BE LGD HGD etc
Risk and benefit to the study participantData on newer imaging method like NBI and AFI are mostly in the form of case series This has not led to a change in the standard of care The early data is very encouraging but not conclusive due to lack of randomized controlled trials Hence we chose a study design of randomized controlled trial of the newer modalities versus the existing conventional endoscopy This design necessitates the performance of a repeat endoscopy Upper endoscopy is very safe routinely done procedure with a low risk of complications A repeat procedure may indeed increase the potential for risks associated with the procedure but the magnitude is small The added advantage of second endoscopy would be increased detection of dysplasia and adenocarcinoma resulting in potential benefit to the patients The main reason for the performance of the current study is the limitation of conventional endoscopy with the implication that dysplasia and adenocarcinoma will be missed on the initial endoscopy In clinical practice this usually warrants a follow up endoscopy that is performed at 1-3 yr intervals due to time and cost constraints For the study population of this trial the second endoscopy has the potential for increased detection of dysplasiaearly adenocarcinoma in the Barretts segment that could lead to initiation of curative therapy
Study PopulationPatients undergoing BE screening and surveillance will be enrolled after written informed consent BE definition- columnar mucosa in the distal esophagus of any length with intestinal metaplasia on biopsy The BE length will be measured from the gastroesophageal junction to the proximally displaced squamo-columnar junction The patient demographics age gender and ethnicity and the BE length will be recorded Total time required for each procedure will be recorded - from endoscope insertion to removal
Narrow Band Imaging Patients will be evaluated with a standard magnification endoscope Olympus GIF Q240Z 115x or GIF-H180 or equivalent using a NBI light source already available at both centers The outer diameter of the endoscope is 108 mm similar to standard diagnostic endoscopes No special processing or cleaning of the endoscope is required - similar to the standard Olympus GIF-100 A cap may or may not be fitted on the distal tip of the endoscope allowing the mucosa in contact with the cap to be magnified without the motility of the esophagus affecting visualization The different patterns will be grouped into ridgevillous circular and irregulardistorted Target biopsies with standard biopsy forceps will be obtained from the different visualized patterns in separate jars
Autofluorescence Imaging Patients will be evaluated using a prototype autofluorescence endoscope Olympus Tokyo Japan excitation 395-475 nm fluorescence detection 490-625 nm red reflectance 600-620 nm and green reflectance 540-560 nm The AFI scope has two different CCD charge coupled device to detect the light waves emittedreflected from the biological tissue - similar to the chip used in a digital camera one for conventional and another for AFI endoscopy There is also a rotary filter that allows blue red or green light to be generated selectively The video processor constructs video images AFI images or normal optical images based on the signals provided by CCD at the distal end of the endoscope In this system normal squamous and non-dysplastic BE appears green while the dysplastic areas appear magentapurplish Targeted biopsies will be obtained from the areas with abnormal fluorescence Both the NBI and AFI equipment will be supplied by Olympus America Inc
Standard Endoscopy Patients will undergo EGD with biopsies using a standard diagnostic video endoscope Olympus GIF 140 or 160 using the Seattle protocol - 4 quadrant biopsies using standard biopsy forceps every 2 cms stored in separate jars
Histology All biopsy specimens will be stained with HE and alcian blue at pH 25 will then be reviewed by two pathologists SM and DL one at each site who will be blinded to the NBIAF results and patterns Any disagreement in the histological diagnosis will be resolved by a consensus diagnosis Dysplasia will be classified as no dysplasia LGD HGD and adenocarcinoma
Data CollectionPatient demographics order of randomization endoscopy findings BE length NBI patterns AFI patterns procedure time number of biopsies and histology reports will be collected and recorded by the study coordinator All this information will be transferred into an ACCESS database
Statistical Power Data AnalysisFor the primary outcome to determine if NBIAFI target biopsies can diagnose BE intestinal metaplasia in 90 of the patients assuming that standard endoscopy with biopsy can diagnose Barretts in 70 we would need 122 patients in order to detect a significant difference between the two with 80 power and a type I error rate of 5 using McNemars test for paired dichotomous responses
For the secondary outcome of detection of HGD will be based on number of biopsies harboring HGD If we assume that NBIAFI can detect areas of HGD within the BE segment in 90 of the biopsies from irregulardistorted patterns compared to 60 by standard endoscopy we would need to study 59 areasbiopsies of HGD in order to detect a significant difference between the two with 80 power and a type 1 error rate of 5 using McNemars test for paired dichotomous responses If we enroll at least 10-12 patients with HGD with an average BE length of 5 cms we will be able to evaluate 60 areas of HGD with each procedure Each site will have to enroll approximately 30-35 BE patients including 5-6 with HGD each year
McNemars test will be used to compare paired categorical data while continuous paired data will be compared using non-parametric methods such as the Wilcoxon Sign Rank Test A p value of 005 will be considered significant
For the initial 30 consecutive patients enrolled in the study inter-observer variability will be studied on the mucosal and vascular patterns and autofluorescence patterns
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