Barrett EsophagusNCT05056051
Wide-Area Transepithelial Sampling in Endoscopic Eradication Therapy for Barrett's Esophagus
A study testing WATS-3D tissue sampling prior to forceps biopsies and WATS-3D tissue sampling following forceps biopsies in people with Barrett Esophagus and Esophageal Cancer, run by Northwestern University at 4 sites in United States.
Trial summary
Esophageal cancer is a deadly disease that is becoming increasingly common in the United States. Barrett's esophagus (BE) is a pre-cancerous state that can develop into esophageal cancer, but is highly treatable. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Barrett Esophagus, Esophageal Cancer
- What is being tested?
- WATS-3D tissue sampling prior to forceps biopsies and WATS-3D tissue sampling following forceps biopsies
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 4 sitesUnited States
- Study dates
- 1 Oct 2020to 30 Jun 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients aged 18+ diagnosed with Barrett's esophagus with confirmed histologic dysplasia or intra-mucosal cancer undergoing surveillance after EET
- Patients who have achieved CE-IM on at least one surveillance endoscopy following EET
- All subjects must have given signed, informed consent prior to registration in the study
Who cannot join
- All patients who are unable or unwilling to give consent will not be included in the study
- All patients deemed to have refractory BE despite EET
- Patients who are pregnant, vulnerable populations such as prisoners, life expectancy < 1 year based on concurrent comorbidities, coagulopathy with INR > 1.5 that cannot be reversed, thrombocytopenia with platelets < 125,000 that cannot be corrected with blood products, unable to safely undergo elective endoscopy due to current comorbidities, and inability to pass standard endoscope will not be included in the study
Trial locations and contacts
4 sites in 1 country.
United States4 sites, 4 recruiting
- Not yet recruiting
University of Colorado
Aurora, Colorado, 80045
Sachin Wani, MD, sachinwani10@yahoo.com
- Recruiting
Northwestern Memorial Hospital
Chicago, Illinois, 60611
Srinadh Komanduri, MD, MS, 312-695-4077, skomandu@nm.org
- Not yet recruiting
University of California, LA
Los Angeles, California, 90095
V Raman Muthusamy, MD, MAS, raman@mednet.ucla.edu
- Not yet recruiting
Washington University in St. Louis, Barnes Jewish Hospital
St Louis, Missouri, 63110
Vladimir Kushnir, MD, vkushnir@wustl.edu
About this study
Official title: Additive Value of Wide-Area Transepithelial Sampling (WATS3D) in Detection of Recurrence of Intestinal Metaplasia Following Endoscopic Eradication Therapy (EET) for Barrett's Esophagus-Related Neoplasia
Esophageal cancer is a deadly disease that is becoming increasingly common in the United States. Barrett's esophagus (BE) is a pre-cancerous state that can develop into esophageal cancer, but is highly treatable. Progression of BE to esophageal cancer is still common due to missed diagnosis of Barrett's esophagus recurrence following treatment. Wide-Area Trans-Epithelial Sampling (WATS-3D) is a new technology that uses brush sampling to examine larger areas of the esophagus as compared to conventional biopsies. Preliminary studies show improved detection of cancerous changes in Barrett's esophagus surveillance. The investigators hope to see if the addition of WATS-3D increases the rate of detection of recurrent BE following treatment, which is of the utmost importance since it would allow for earlier re-treatment of disease and ultimately allow for prevention of progression to esophageal cancer.
Read the detailed description
Barrett's esophagus (BE) affects 5-15% of all patients with gastroesophageal reflux disease and approximately 1-2% of the entire population. The stepwise progression of BE from intestinal metaplasia (IM) to dysplasia can ultimately lead to esophageal adenocarcinoma (EAC). There are over 15,000 cases of EAC diagnosed in the United States each year. Regardless of stage of disease at time of diagnosis, the 5-year survival for EAC is an abysmal 19%. Endoscopic eradication therapy (EET) has been shown to be very effective in preventing progression of dysplastic BE to EAC with rates of complete eradication of intestinal metaplasia (CE-IM) > 90%. This is of paramount importance given the poor outcomes associated with the development of EAC.
Despite high success rates in achieving CE-IM, recent studies show that the recurrence of IM following CE-IM occurs with annual incidence of 8-10% and a 2-3% dysplasia rate per patient year of follow-up. The current paradigm of endoscopic surveillance following CE-IM focuses on random biopsies, which has raised concerns about sampling error and missed recurrence of IM and dysplasia leading to increased risk of interval development of EAC. New technologies, such as Wide-Area Trans-Epithelial Sampling (WATS-3D; CDx Diagnostics, Suffern, NY) have been studied to improve detection of dysplasia in BE. WATS-3D involves abrasive brush sampling of the esophagus that is then processed by a validated computer imaging system and subsequently reviewed by pathologist. Prior studies have shown increased dysplasia detection in routine BE surveillance with WATS-3D over standard biopsies, however there are no published data as to the additive value of WATS-3D for detection of recurrence of disease after endoscopic therapy.
Problem Statement:
Despite high success rates of successful eradication of BE with EET, recurrence rates are still high. Current Seattle Protocol biopsies for Post-EET surveillance is time-consuming, difficult to reproduce, and often misses IM recurrence putting patients at increased risk of developing EAC.
Hypothesis and Specific Aims:
The investigators hypothesize that the addition of WATS-3D to standard four-quadrant biopsies driven by HD-WLE and Narrow Band Imaging (NBI) will increase the rate of detection of recurrence of IM and dysplasia in patients who have undergone EET. To that end, increased recurrent IM detection will allow for proper choice of repeat EET and decreased progression to EAC. The specific aims:
- To assess the additive diagnostic yield of WATS-3D sampling beyond that of standard biopsies for detection of IM or dysplasia (recurrence) in patients who have undergone EET for BE-related neoplasia.
- To assess the difference in additive diagnostic yield of WATS-3D sampling beyond that of standard biopsies between CE-IM as defined by a single exam without IM vs. >1 exam
- To assess the impact of order of tissue acquisition techniques on detection of recurrent IM or dysplasia (via randomization)
The proposed study will be a prospective multi-center design over 24 months. The participating centers will include Northwestern University, Washington University in St. Louis, University of Colorado and University of California, Los Angeles.
- A total of 200 patients will be in enrolled in this prospective study. All patients who have completed EET with at least one endoscopy with biopsies demonstrating no evidence of IM will be eligible for enrollment in the study. Enrollment will occur in the setting of outpatient clinic visit or in the endoscopy lab. The PI or study coordinator will meet with the patient and discuss the study, its objectives, and expectations and informed consent will be obtained.
- Enrolled subjects will have completed EET as per clinical standard of care within the framework of the following study design. Standard EET will be defined as resection of visible lesions and ablative therapy (either radio frequency ablation or cryo-therapy). Once complete eradication of intestinal metaplasia (CE-IM) is achieved as defined as no recurrence of BE endoscopically or on forceps biopsies for at least a single EGD, patients will then undergo post-EET surveillance.
- While adhering to standard post-EET surveillance endoscopy intervals, on a prospective basis, the investigators will add WATS-3D to the surveillance protocol. Each patient will be randomized to one of two groups. The first group will undergo biopsies with standard forceps first, followed by tissue sampling with WATS-3D. The second group will undergo tissue sampling with WATS-3D first, followed by biopsies with standard forceps. The forceps biopsies will then be examined by expert pathologists at each respective institution, while the WATS-3D samples will be evaluated at a central laboratory. Each surveillance endoscopy will follow current standard inspection with HD-WLE and NBI. Forceps biopsies will be obtained from: a) the gastric cardia, b) the new squamocolumnar junction, and c) targeted/neosquamous sampling of the original BE segment. WATS-3D brushing will be performed of the: a) squamocolumnar junction to include and visible islands and b) the neosquamous zone representative of the original BE segment. WATS-3D brushings will be taken in 5 cm esophageal segments of the neo-squamous mucosa.
- All physicians will participate in a training session (virtual) which will discuss the use of WATS-3D and ensure all sampling is standardized.
- Once a patient is randomized, all subsequent surveillance endoscopies will follow the same tissue sampling order. For instance, if a patient is assigned to the group that will undergo tissue sampling with WATS-3D first, followed by biopsies with standard forceps second, all surveillance endoscopies will follow sampling in this order. Patients will continue in the study for 2 consecutive endoscopies using this sampling protocol. All patients will be followed longitudinally for the duration of their endoscopy surveillance.
- The investigators will then compare the detection of IM and dysplastic cells obtained via Seattle Protocol biopsies to WATS-3D obtained samples.
- Conditions
- Barrett Esophagus, Esophageal Cancer
- Being tested
- WATS-3D tissue sampling prior to forceps biopsies, WATS-3D tissue sampling following forceps biopsies
- Medical subject headings
- Barrett Esophagus, Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
WATS-3D tissue sampling prior to forceps biopsiesDevice
WATS-3D is a brush-based tissue sampling technique. Abrasive brush sampling of large areas of the esophagus pick up cells to obtain trans-epithelial specimens. This technique samples much larger tissue areas than standard forceps biopsies. Analysis is then done by proprietary neural-network based computer scanning and molecular diagnostics to identify abnormal cells.
WATS-3D tissue sampling following forceps biopsiesDevice
WATS-3D is a brush-based tissue sampling technique. Abrasive brush sampling of large areas of the esophagus pick up cells to obtain trans-epithelial specimens. This technique samples much larger tissue areas than standard forceps biopsies. Analysis is then done by proprietary neural-network based computer scanning and molecular diagnostics to identify abnormal cells. This will be done after forceps biopsies in this arm.
| Study group | Role | What they receive |
|---|---|---|
| Post-EET Surveillance Group: WATS-3D samples followed by Forceps biopsies | Active comparator | Sampling will occur with WATS-3D followed by forceps biopsies. For each patient, resection samples will be identified by the endoscopy method used to locate the sample as either HD-WLE/NBI or WATS-3D. For each method of detection, the highest grade of histology for each patient will be assigned based on the identified samples. Dysplasia detected on random biopsies will be attributed HD-WLE/NBI given it is part of the standard of care. Receives: Device: WATS-3D tissue sampling prior to forceps biopsies |
| Post-EET Surveillance Group: Forceps biopsies followed by WATS-3D samples | Active comparator | Sampling will occur with forceps biopsies followed by WATS-3D. For each patient, resection samples will be identified by the endoscopy method used to locate the sample as either HD-WLE/NBI or WATS-3D. For each method of detection, the highest grade of histology for each patient will be assigned based on the identified samples. Dysplasia detected on random biopsies will be attributed HD-WLE/NBI given it is part of the standard of care. Receives: Device: WATS-3D tissue sampling following forceps biopsies |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the additive diagnostic yield as assessed by proportion of patients with recurrence be use of WATS-3D
To assess the additive diagnostic yield of WATS-3D sampling beyond that of standard biopsies for detection of IM or dysplasia (recurrence) in patients who have undergone EET for BE-related neoplasia. The rates of recurrence as determined by the proportion of patients (percentage) deemed to have recurrence of BE on tissue sampling will be compared between samples obtained by WATS-3D vs forceps biopsies.
Measured: 2 years
Secondary outcomes (2)
To assess if there is a difference in diagnostic yield of WATS-3D based on CE-IM definition between one and two or more endoscopies
To assess the difference in additive diagnostic yield of WATS-3D sampling beyond that of standard biopsies between CE-IM, the proportion of patients with recurrence will be compared based if CE-IM was based on a single exam without IM vs. two or more successive exams without IM.
Measured: 3 years
To assess if the order by which tissue is sampled affects the diagnostic yield of WATS-3D by comparing the proportion of patients with recurrence between groups.
It is unclear if there is any impact of order of tissue acquisition techniques on detection of recurrent IM or dysplasia. By randomizing patients to either WATS-3D first followed by forceps biopsies vs forceps biopsies followed by WATS-3D, the proportion of patients with recurrence will be compared to see if the order of sampling affects the proportion of patients found to have recurrent BE.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2021
- Study start1 Oct 2020
- Primary completion30 Jun 2025 (estimated)
- Study completion30 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for Barrett EsophagusStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- All patients enrolled will have neo-squamous segment tested with WATS-3D and biopsy forceps
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- Washington University School of Medicine, University of Colorado, Denver, University of California, Los Angeles
- Responsible party
- Sponsor
- Investigators
- Srinadh Komanduri, Principal investigator, Feinberg School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05056051
- Sponsor's protocol ID
- STU00200319-2
- Status last verified
- Apr 2024
- First submitted
- 4 Mar 2021
- Last updated
- 24 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Publications
Rastogi A, Puli S, El-Serag HB, Bansal A, Wani S, Sharma P. Incidence of esophageal adenocarcinoma in patients with Barrett's esophagus and high-grade dysplasia: a meta-analysis. Gastrointest Endosc. 2008 Mar;67(3):394-8. doi: 10.1016/j.gie.2007.07.019. Epub 2007 Nov 28.
PubMed 18045592Runge TM, Abrams JA, Shaheen NJ. Epidemiology of Barrett's Esophagus and Esophageal Adenocarcinoma. Gastroenterol Clin North Am. 2015 Jun;44(2):203-31. doi: 10.1016/j.gtc.2015.02.001. Epub 2015 Apr 9.
PubMed 26021191ASGE STANDARDS OF PRACTICE COMMITTEE; Qumseya B, Sultan S, Bain P, Jamil L, Jacobson B, Anandasabapathy S, Agrawal D, Buxbaum JL, Fishman DS, Gurudu SR, Jue TL, Kripalani S, Lee JK, Khashab MA, Naveed M, Thosani NC, Yang J, DeWitt J, Wani S; ASGE Standards of Practice Committee Chair. ASGE guideline on screening and surveillance of Barrett's esophagus. Gastrointest Endosc. 2019 Sep;90(3):335-359.e2. doi: 10.1016/j.gie.2019.05.012. No abstract available.
PubMed 31439127Reed CC, Shaheen NJ. Natural History of the Post-ablation Esophagus. Dig Dis Sci. 2018 Aug;63(8):2136-2145. doi: 10.1007/s10620-018-5066-8.
PubMed 29671157Phoa KN, Pouw RE, van Vilsteren FGI, Sondermeijer CMT, Ten Kate FJW, Visser M, Meijer SL, van Berge Henegouwen MI, Weusten BLAM, Schoon EJ, Mallant-Hent RC, Bergman JJGHM. Remission of Barrett's esophagus with early neoplasia 5 years after radiofrequency ablation with endoscopic resection: a Netherlands cohort study. Gastroenterology. 2013 Jul;145(1):96-104. doi: 10.1053/j.gastro.2013.03.046. Epub 2013 Mar 28.
PubMed 23542068Yousef F, Cardwell C, Cantwell MM, Galway K, Johnston BT, Murray L. The incidence of esophageal cancer and high-grade dysplasia in Barrett's esophagus: a systematic review and meta-analysis. Am J Epidemiol. 2008 Aug 1;168(3):237-49. doi: 10.1093/aje/kwn121. Epub 2008 Jun 12.
PubMed 18550563Kia L, Komanduri S. Care of the Postablation Patient: Surveillance, Acid Suppression, and Treatment of Recurrence. Gastrointest Endosc Clin N Am. 2017 Jul;27(3):515-529. doi: 10.1016/j.giec.2017.02.008.
PubMed 28577772Anders M, Bahr C, El-Masry MA, Marx AH, Koch M, Seewald S, Schachschal G, Adler A, Soehendra N, Izbicki J, Neuhaus P, Pohl H, Rosch T. Long-term recurrence of neoplasia and Barrett's epithelium after complete endoscopic resection. Gut. 2014 Oct;63(10):1535-43. doi: 10.1136/gutjnl-2013-305538. Epub 2014 Jan 3.
PubMed 24389236Desai M, Saligram S, Gupta N, Vennalaganti P, Bansal A, Choudhary A, Vennelaganti S, He J, Titi M, Maselli R, Qumseya B, Olyaee M, Waxman I, Repici A, Hassan C, Sharma P. Efficacy and safety outcomes of multimodal endoscopic eradication therapy in Barrett's esophagus-related neoplasia: a systematic review and pooled analysis. Gastrointest Endosc. 2017 Mar;85(3):482-495.e4. doi: 10.1016/j.gie.2016.09.022. Epub 2016 Sep 23.
PubMed 27670227Fujii-Lau LL, Cinnor B, Shaheen N, Gaddam S, Komanduri S, Muthusamy VR, Das A, Wilson R, Simon VC, Kushnir V, Mullady D, Edmundowicz SA, Early DS, Wani S. Recurrence of intestinal metaplasia and early neoplasia after endoscopic eradication therapy for Barrett's esophagus: a systematic review and meta-analysis. Endosc Int Open. 2017 Jun;5(6):E430-E449. doi: 10.1055/s-0043-106578. Epub 2017 May 31.
PubMed 28573176Wani S, Muthusamy VR, Shaheen NJ, Yadlapati R, Wilson R, Abrams JA, Bergman J, Chak A, Chang K, Das A, Dumot J, Edmundowicz SA, Eisen G, Falk GW, Fennerty MB, Gerson L, Ginsberg GG, Grande D, Hall M, Harnke B, Inadomi J, Jankowski J, Lightdale CJ, Makker J, Odze RD, Pech O, Sampliner RE, Spechler S, Triadafilopoulos G, Wallace MB, Wang K, Waxman I, Komanduri S. Development of quality indicators for endoscopic eradication therapies in Barrett's esophagus: the TREAT-BE (Treatment with Resection and Endoscopic Ablation Techniques for Barrett's Esophagus) Consortium. Gastrointest Endosc. 2017 Jul;86(1):1-17.e3. doi: 10.1016/j.gie.2017.03.010. Epub 2017 May 30. No abstract available.
PubMed 28576294Cotton CC, Haidry R, Thrift AP, Lovat L, Shaheen NJ. Development of Evidence-Based Surveillance Intervals After Radiofrequency Ablation of Barrett's Esophagus. Gastroenterology. 2018 Aug;155(2):316-326.e6. doi: 10.1053/j.gastro.2018.04.011. Epub 2018 Apr 13.
PubMed 29655833Cotton CC, Wolf WA, Overholt BF, Li N, Lightdale CJ, Wolfsen HC, Pasricha S, Wang KK, Shaheen NJ; AIM Dysplasia Trial Group. Late Recurrence of Barrett's Esophagus After Complete Eradication of Intestinal Metaplasia is Rare: Final Report From Ablation in Intestinal Metaplasia Containing Dysplasia Trial. Gastroenterology. 2017 Sep;153(3):681-688.e2. doi: 10.1053/j.gastro.2017.05.044. Epub 2017 Jun 1.
PubMed 28579538Smith MS, Ikonomi E, Bhuta R, Iorio N, Kataria RD, Kaul V, Gross SA; US Collaborative WATS Study Group. Wide-area transepithelial sampling with computer-assisted 3-dimensional analysis (WATS) markedly improves detection of esophageal dysplasia and Barrett's esophagus: analysis from a prospective multicenter community-based study. Dis Esophagus. 2019 Mar 1;32(3):doy099. doi: 10.1093/dote/doy099.
PubMed 30541019Vennalaganti PR, Kaul V, Wang KK, Falk GW, Shaheen NJ, Infantolino A, Johnson DA, Eisen G, Gerson LB, Smith MS, Iyer PG, Lightdale CJ, Schnoll-Sussman F, Gupta N, Gross SA, Abrams J, Haber GB, Chuttani R, Pleskow DK, Kothari S, Goldblum JR, Zhang Y, Sharma P. Increased detection of Barrett's esophagus-associated neoplasia using wide-area trans-epithelial sampling: a multicenter, prospective, randomized trial. Gastrointest Endosc. 2018 Feb;87(2):348-355. doi: 10.1016/j.gie.2017.07.039. Epub 2017 Jul 27.
PubMed 28757316
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Additive Value of Wide-Area Transepithelial Sampling (WATS3D) in Detection of Recurrence of Intestinal Metaplasia Following Endoscopic Eradication Therapy (EET) for Barrett's Esophagus-Related Neoplasia
- ClinicalTrials.gov ID
- NCT05056051
- Acronym / sponsor ID
- STU00200319-2
- Conditions
- Barrett Esophagus, Esophageal Cancer
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- Washington University School of Medicine, University of Colorado, Denver, University of California, Los Angeles
- Study start
- 1 Oct 2020 (actual)
- Primary completion
- 30 Jun 2025 (estimated)
- Study completion
- 30 Jun 2025 (estimated)
- First posted
- 24 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Esophageal cancer is a deadly disease that is becoming increasingly common in the United States. Barrett's esophagus (BE) is a pre-cancerous state that can develop into esophageal cancer, but is highly treatable. Progression of BE to esophageal cancer is still common due to missed diagnosis of Barrett's esophagus recurrence following treatment. Wide-Area Trans-Epithelial Sampling (WATS-3D) is a new technology that uses brush sampling to examine larger areas of the esophagus as compared to conventional biopsies. Preliminary studies show improved detection of cancerous changes in Barrett's esophagus surveillance. The investigators hope to see if the addition of WATS-3D increases the rate of detection of recurrent BE following treatment, which is of the utmost importance since it would allow for earlier re-treatment of disease and ultimately allow for prevention of progression to esophageal cancer.
Detailed description
Barrett's esophagus (BE) affects 5-15% of all patients with gastroesophageal reflux disease and approximately 1-2% of the entire population. The stepwise progression of BE from intestinal metaplasia (IM) to dysplasia can ultimately lead to esophageal adenocarcinoma (EAC). There are over 15,000 cases of EAC diagnosed in the United States each year. Regardless of stage of disease at time of diagnosis, the 5-year survival for EAC is an abysmal 19%. Endoscopic eradication therapy (EET) has been shown to be very effective in preventing progression of dysplastic BE to EAC with rates of complete eradication of intestinal metaplasia (CE-IM) > 90%. This is of paramount importance given the poor outcomes associated with the development of EAC.
Despite high success rates in achieving CE-IM, recent studies show that the recurrence of IM following CE-IM occurs with annual incidence of 8-10% and a 2-3% dysplasia rate per patient year of follow-up. The current paradigm of endoscopic surveillance following CE-IM focuses on random biopsies, which has raised concerns about sampling error and missed recurrence of IM and dysplasia leading to increased risk of interval development of EAC. New technologies, such as Wide-Area Trans-Epithelial Sampling (WATS-3D; CDx Diagnostics, Suffern, NY) have been studied to improve detection of dysplasia in BE. WATS-3D involves abrasive brush sampling of the esophagus that is then processed by a validated computer imaging system and subsequently reviewed by pathologist. Prior studies have shown increased dysplasia detection in routine BE surveillance with WATS-3D over standard biopsies, however there are no published data as to the additive value of WATS-3D for detection of recurrence of disease after endoscopic therapy.
Problem Statement:
Despite high success rates of successful eradication of BE with EET, recurrence rates are still high. Current Seattle Protocol biopsies for Post-EET surveillance is time-consuming, difficult to reproduce, and often misses IM recurrence putting patients at increased risk of developing EAC.
Hypothesis and Specific Aims:
The investigators hypothesize that the addition of WATS-3D to standard four-quadrant biopsies driven by HD-WLE and Narrow Band Imaging (NBI) will increase the rate of detection of recurrence of IM and dysplasia in patients who have undergone EET. To that end, increased recurrent IM detection will allow for proper choice of repeat EET and decreased progression to EAC. The specific aims:
- To assess the additive diagnostic yield of WATS-3D sampling beyond that of standard biopsies for detection of IM or dysplasia (recurrence) in patients who have undergone EET for BE-related neoplasia.
- To assess the difference in additive diagnostic yield of WATS-3D sampling beyond that of standard biopsies between CE-IM as defined by a single exam without IM vs. >1 exam
- To assess the impact of order of tissue acquisition techniques on detection of recurrent IM or dysplasia (via randomization)
The proposed study will be a prospective multi-center design over 24 months. The participating centers will include Northwestern University, Washington University in St. Louis, University of Colorado and University of California, Los Angeles.
- A total of 200 patients will be in enrolled in this prospective study. All patients who have completed EET with at least one endoscopy with biopsies demonstrating no evidence of IM will be eligible for enrollment in the study. Enrollment will occur in the setting of outpatient clinic visit or in the endoscopy lab. The PI or study coordinator will meet with the patient and discuss the study, its objectives, and expectations and informed consent will be obtained.
- Enrolled subjects will have completed EET as per clinical standard of care within the framework of the following study design. Standard EET will be defined as resection of visible lesions and ablative therapy (either radio frequency ablation or cryo-therapy). Once complete eradication of intestinal metaplasia (CE-IM) is achieved as defined as no recurrence of BE endoscopically or on forceps biopsies for at least a single EGD, patients will then undergo post-EET surveillance.
- While adhering to standard post-EET surveillance endoscopy intervals, on a prospective basis, the investigators will add WATS-3D to the surveillance protocol. Each patient will be randomized to one of two groups. The first group will undergo biopsies with standard forceps first, followed by tissue sampling with WATS-3D. The second group will undergo tissue sampling with WATS-3D first, followed by biopsies with standard forceps. The forceps biopsies will then be examined by expert pathologists at each respective institution, while the WATS-3D samples will be evaluated at a central laboratory. Each surveillance endoscopy will follow current standard inspection with HD-WLE and NBI. Forceps biopsies will be obtained from: a) the gastric cardia, b) the new squamocolumnar junction, and c) targeted/neosquamous sampling of the original BE segment. WATS-3D brushing will be performed of the: a) squamocolumnar junction to include and visible islands and b) the neosquamous zone representative of the original BE segment. WATS-3D brushings will be taken in 5 cm esophageal segments of the neo-squamous mucosa.
- All physicians will participate in a training session (virtual) which will discuss the use of WATS-3D and ensure all sampling is standardized.
- Once a patient is randomized, all subsequent surveillance endoscopies will follow the same tissue sampling order. For instance, if a patient is assigned to the group that will undergo tissue sampling with WATS-3D first, followed by biopsies with standard forceps second, all surveillance endoscopies will follow sampling in this order. Patients will continue in the study for 2 consecutive endoscopies using this sampling protocol. All patients will be followed longitudinally for the duration of their endoscopy surveillance.
- The investigators will then compare the detection of IM and dysplastic cells obtained via Seattle Protocol biopsies to WATS-3D obtained samples.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- All patients enrolled will have neo-squamous segment tested with WATS-3D and biopsy forceps
| Arm | Type | Receives |
|---|---|---|
| Post-EET Surveillance Group: WATS-3D samples followed by Forceps biopsies | Active comparator | Device: WATS-3D tissue sampling prior to forceps biopsiesSampling will occur with WATS-3D followed by forceps biopsies. For each patient, resection samples will be identified by the endoscopy method used to locate the sample as either HD-WLE/NBI or WATS-3D. For each method of detection, the highest grade of histology for each patient will be assigned based on the identified samples. Dysplasia detected on random biopsies will be attributed HD-WLE/NBI given it is part of the standard of care. |
| Post-EET Surveillance Group: Forceps biopsies followed by WATS-3D samples | Active comparator | Device: WATS-3D tissue sampling following forceps biopsiesSampling will occur with forceps biopsies followed by WATS-3D. For each patient, resection samples will be identified by the endoscopy method used to locate the sample as either HD-WLE/NBI or WATS-3D. For each method of detection, the highest grade of histology for each patient will be assigned based on the identified samples. Dysplasia detected on random biopsies will be attributed HD-WLE/NBI given it is part of the standard of care. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- All patients aged 18+ diagnosed with Barrett's esophagus with confirmed histologic dysplasia or intra-mucosal cancer undergoing surveillance after EET
- Patients who have achieved CE-IM on at least one surveillance endoscopy following EET
- All subjects must have given signed, informed consent prior to registration in the study
Key exclusion criteria (3 listed)
- All patients who are unable or unwilling to give consent will not be included in the study
- All patients deemed to have refractory BE despite EET
- Patients who are pregnant, vulnerable populations such as prisoners, life expectancy < 1 year based on concurrent comorbidities, coagulopathy with INR > 1.5 that cannot be reversed, thrombocytopenia with platelets < 125,000 that cannot be corrected with blood products, unable to safely undergo elective endoscopy due to current comorbidities, and inability to pass standard endoscope will not be included in the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| WATS-3D tissue sampling prior to forceps biopsiesWATS-3D is a brush-based tissue sampling technique. Abrasive brush sampling of large areas of the esophagus pick up cells to obtain trans-epithelial specimens. This technique samples much larger tissue areas than standard forceps biopsies. Analysis is then done by proprietary neural-network based computer scanning and molecular diagnostics to identify abnormal cells. | Device | Post-EET Surveillance Group: WATS-3D samples followed by Forceps biopsies |
| WATS-3D tissue sampling following forceps biopsiesWATS-3D is a brush-based tissue sampling technique. Abrasive brush sampling of large areas of the esophagus pick up cells to obtain trans-epithelial specimens. This technique samples much larger tissue areas than standard forceps biopsies. Analysis is then done by proprietary neural-network based computer scanning and molecular diagnostics to identify abnormal cells. This will be done after forceps biopsies in this arm. | Device | Post-EET Surveillance Group: Forceps biopsies followed by WATS-3D samples |
Primary outcome
To assess the additive diagnostic yield as assessed by proportion of patients with recurrence be use of WATS-3D
Time frame: 2 years
To assess the additive diagnostic yield of WATS-3D sampling beyond that of standard biopsies for detection of IM or dysplasia (recurrence) in patients who have undergone EET for BE-related neoplasia. The rates of recurrence as determined by the proportion of patients (percentage) deemed to have recurrence of BE on tissue sampling will be compared between samples obtained by WATS-3D vs forceps biopsies.
2 secondary outcomes
To assess if there is a difference in diagnostic yield of WATS-3D based on CE-IM definition between one and two or more endoscopies
Time frame: 3 years
To assess if the order by which tissue is sampled affects the diagnostic yield of WATS-3D by comparing the proportion of patients with recurrence between groups.
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2024.
- Background: PubMed 18045592Rastogi A, Puli S, El-Serag HB, Bansal A, Wani S, Sharma P. Incidence of esophageal adenocarcinoma in patients with Barrett's esophagus and high-grade dysplasia: a meta-analysis. Gastrointest Endosc. 2008 Mar;67(3):394-8. doi: 10.1016/j.gie.2007.07.019. Epub 2007 Nov 28.
- Background: PubMed 26021191Runge TM, Abrams JA, Shaheen NJ. Epidemiology of Barrett's Esophagus and Esophageal Adenocarcinoma. Gastroenterol Clin North Am. 2015 Jun;44(2):203-31. doi: 10.1016/j.gtc.2015.02.001. Epub 2015 Apr 9.
- Background: PubMed 31439127ASGE STANDARDS OF PRACTICE COMMITTEE; Qumseya B, Sultan S, Bain P, Jamil L, Jacobson B, Anandasabapathy S, Agrawal D, Buxbaum JL, Fishman DS, Gurudu SR, Jue TL, Kripalani S, Lee JK, Khashab MA, Naveed M, Thosani NC, Yang J, DeWitt J, Wani S; ASGE Standards of Practice Committee Chair. ASGE guideline on screening and surveillance of Barrett's esophagus. Gastrointest Endosc. 2019 Sep;90(3):335-359.e2. doi: 10.1016/j.gie.2019.05.012. No abstract available.
- Background: PubMed 29671157Reed CC, Shaheen NJ. Natural History of the Post-ablation Esophagus. Dig Dis Sci. 2018 Aug;63(8):2136-2145. doi: 10.1007/s10620-018-5066-8.
- Background: PubMed 23542068Phoa KN, Pouw RE, van Vilsteren FGI, Sondermeijer CMT, Ten Kate FJW, Visser M, Meijer SL, van Berge Henegouwen MI, Weusten BLAM, Schoon EJ, Mallant-Hent RC, Bergman JJGHM. Remission of Barrett's esophagus with early neoplasia 5 years after radiofrequency ablation with endoscopic resection: a Netherlands cohort study. Gastroenterology. 2013 Jul;145(1):96-104. doi: 10.1053/j.gastro.2013.03.046. Epub 2013 Mar 28.
- Background: PubMed 18550563Yousef F, Cardwell C, Cantwell MM, Galway K, Johnston BT, Murray L. The incidence of esophageal cancer and high-grade dysplasia in Barrett's esophagus: a systematic review and meta-analysis. Am J Epidemiol. 2008 Aug 1;168(3):237-49. doi: 10.1093/aje/kwn121. Epub 2008 Jun 12.
- Background: PubMed 28577772Kia L, Komanduri S. Care of the Postablation Patient: Surveillance, Acid Suppression, and Treatment of Recurrence. Gastrointest Endosc Clin N Am. 2017 Jul;27(3):515-529. doi: 10.1016/j.giec.2017.02.008.
- Background: PubMed 24389236Anders M, Bahr C, El-Masry MA, Marx AH, Koch M, Seewald S, Schachschal G, Adler A, Soehendra N, Izbicki J, Neuhaus P, Pohl H, Rosch T. Long-term recurrence of neoplasia and Barrett's epithelium after complete endoscopic resection. Gut. 2014 Oct;63(10):1535-43. doi: 10.1136/gutjnl-2013-305538. Epub 2014 Jan 3.
- Background: PubMed 27670227Desai M, Saligram S, Gupta N, Vennalaganti P, Bansal A, Choudhary A, Vennelaganti S, He J, Titi M, Maselli R, Qumseya B, Olyaee M, Waxman I, Repici A, Hassan C, Sharma P. Efficacy and safety outcomes of multimodal endoscopic eradication therapy in Barrett's esophagus-related neoplasia: a systematic review and pooled analysis. Gastrointest Endosc. 2017 Mar;85(3):482-495.e4. doi: 10.1016/j.gie.2016.09.022. Epub 2016 Sep 23.
- Background: PubMed 28573176Fujii-Lau LL, Cinnor B, Shaheen N, Gaddam S, Komanduri S, Muthusamy VR, Das A, Wilson R, Simon VC, Kushnir V, Mullady D, Edmundowicz SA, Early DS, Wani S. Recurrence of intestinal metaplasia and early neoplasia after endoscopic eradication therapy for Barrett's esophagus: a systematic review and meta-analysis. Endosc Int Open. 2017 Jun;5(6):E430-E449. doi: 10.1055/s-0043-106578. Epub 2017 May 31.
- Background: PubMed 28576294Wani S, Muthusamy VR, Shaheen NJ, Yadlapati R, Wilson R, Abrams JA, Bergman J, Chak A, Chang K, Das A, Dumot J, Edmundowicz SA, Eisen G, Falk GW, Fennerty MB, Gerson L, Ginsberg GG, Grande D, Hall M, Harnke B, Inadomi J, Jankowski J, Lightdale CJ, Makker J, Odze RD, Pech O, Sampliner RE, Spechler S, Triadafilopoulos G, Wallace MB, Wang K, Waxman I, Komanduri S. Development of quality indicators for endoscopic eradication therapies in Barrett's esophagus: the TREAT-BE (Treatment with Resection and Endoscopic Ablation Techniques for Barrett's Esophagus) Consortium. Gastrointest Endosc. 2017 Jul;86(1):1-17.e3. doi: 10.1016/j.gie.2017.03.010. Epub 2017 May 30. No abstract available.
- Background: PubMed 29655833Cotton CC, Haidry R, Thrift AP, Lovat L, Shaheen NJ. Development of Evidence-Based Surveillance Intervals After Radiofrequency Ablation of Barrett's Esophagus. Gastroenterology. 2018 Aug;155(2):316-326.e6. doi: 10.1053/j.gastro.2018.04.011. Epub 2018 Apr 13.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Srinadh Komanduri principal investigator
Feinberg School of Medicine
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing WATS-3D tissue sampling prior to forceps biopsies and WATS-3D tissue sampling following forceps biopsies in people with Barrett Esophagus and Esophageal Cancer, run by Northwestern University at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Srinadh Komanduri, MD, MS (3126950484, skomandu@nm.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess the additive diagnostic yield as assessed by proportion of patients with recurrence be use of WATS-3D (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05056051, which also lists 17 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2024.