Neoplasms

Digestive System Diseases

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Barrett Esophagus

Precancerous Conditions

Esophageal Diseases

Gastrointestinal Diseases

IVLCM tethered capsule for obtaining biopsies for genomic sequencing of BE for the assessment of EAC risk.

Obtaining biopsies for genomic sequencing of BE for the assessment of EAC risk using IVLCM tethered capsule

IVLCM tethered capsule

Anita Chung, RN

Elizabeth Biddle, RN

Gary Tearney, MD., PhD

The investigators have developed a new technology, termed in-vivo laser capture microdissection (IVLCM), that addresses the limitations of endoscopic biopsy for screening for BE and provides targeted genomic profiling of aberrant tissue for more precise prediction of EAC risk. The device is a tethered capsule endomicroscope (TCE) that implements optical coherence tomography (OCT) to grab 10-mm-resolution, cross-sectional microscopic images of the entire esophagus after the capsule is swallowed. This OCT-based TCE technology is used in unsedated patients to visualize images of BE and dysplastic BE. During the IVLCM procedure, TCE images of abnormal BE tissue are identified in real time and selectively adhered onto the device. When the capsule is removed from the patient, these tissues, targeted based on their abnormal OCT morphology, are sent for genomic analysis. By enabling the precise isolation of aberrant esophageal tissues using a swallowable capsule, this technology has the potential to solve the major problems that currently prohibit adequate BE screening and prevention of Esophageal Adenocarcinoma EAC.

In Vivo Laser Capture Microdissection (IVLCM). The IVLCM tethered capsule is identical to those used in current approved OCT TCE studies.The capsule is swallowed by the patient and then, in real time, a region for tissue capture, is identified on the images. When a targeted site is identified, a capture laser (1450 nm, 0.8 W, 1 second exposure; within the range of the previously approved OCT-TCE tissue marking study) irradiates this area in the patient, heating the water in the tissue and transforming it to steam. The accumulated water steam overcomes the tissue matrix's adhesion force, ejecting a small amount of tissue and integrating it with the capsule's external shell. This process may then be repeated to collect multiple samples. After the device is pulled out from the patient, the captured tissues can be extracted for genomic analysis. Ex vivo animal tissue studies have shown that capture laser does not damage DNA/RNA; high quality whole genome information can be obtained.

In this IVLCM study, the investigators are using a 1450 nm laser to capture tissue that was previously approved to make cautery "marks" in the esophagus. The IVLCM capture laser's specifications are the same as those of the marking laser and the power will be within the IRB approved power range (0.82 W 1s). Prior to testing laser marking in humans, the investigators first demonstrated the safety of laser marking in animals in vivo. Histological assessment showed that the cautery marks did not penetrate through the submucosa and the vast majority of the effects were limited to the epithelium, lamina propria, and muscularis mucosa layers. The extent of thermal damage was comparable to conventional biopsies in standard of care endoscopic biopsy procedures. After this animal study, the investigators conducted a pilot study in humans in which over 30 marks were made in 22 enrolled subjects without any adverse events or safety concerns. In addition to these balloon studies, the investigators are currently conducting a TCE marking study. So far, the investigators have imaged and marked 13 subjects through a capsule without any adverse effects or safety concerns.

Thirty (N=30) subjects will be enrolled in this study.

Pilot Study for OCT Guided In Vivo Laser Capture Microdissection for Assessing the Prognosis of Barrett's Esophagus

We will measure the number of subjects from which we will be able to collect biopsy samples using IVLCM technique

National Institutes of Health (NIH)

National Institute for Biomedical Imaging and Bioengineering (NIBIB)

Massachusetts General Hospital

Principal Investigator

Subject will swallow the OFDI capsule and imaging will be acquired using the OFDI imaging system.

Intervention: 'Tethered Capsule Endomicroscopy (TCE) Imaging of Barrett's esophagus using OFDI capsule

Tethered Capsule Endomicroscopy will be used to detect Barrett's Esophagus

Tethered Capsule Endomicroscopy (TCE)

Guillermo Tearney, MD, PhD

The goal of this research is to follow Barrett's Esophagus patients for 3 years using the tethered capsule endomicroscopy device with distal scanning and a compact imaging system in a multi-site clinical study.

The progression of Barrett's Esophagus will be studied over time using tethered capsule endomicroscopy imaging and will be performed at 5 different clinical centers in the US, namely: Massachusetts General Hospital (MGH),(MA), Mayo Clinic Jacksonville (FL), Mayo Clinic Rochester (MN), Columbia University Medical Center (NY), Kansas City VA Medical Center (MO). MGH will be the coordinating center of this multicenter study. Dr G. Tearney will serve as study Sponsor Investigator.

The purpose of this study is to determine the natural history of Barrett's Esophagus using TCE in subjects diagnosed with Barrett's Esophagus and undergoing surveillance endoscopy.

A hundred patients are enrolled in year 1 in each of five participating centers.

Coordinating Center: Natural History of Barrett's Esophagus Using Tethered Capsule Endomicroscopy

We will be measuring the size of the area affected by Barrett's. The measurements will done in cm.

Columbia University

Mayo Clinic

Kansas City Veteran Affairs Medical Center

National Cancer Institute (NCI)

Professor of Pathology, HMS

1. Feasibility of using tethered capsule endomicroscopy as a screening method for Barrett's esophagus in the primary care practice environment
2. Determine the prevalence of Barrett's esophagus in a primary care practice cohort at MGH

Participants will be asked to swallow the TCE device. Participants may use mild numbing spray, and lubrication spray to help swallowing. Imaging will be conducted once the TCE device is past the pharynx. The TCE device will be advanced until the stomach and then slowly pull the TCE back up the esophagus. This may be repeated twice.

Tethered Capsule Endomicroscopy

Guillermo Tearney, M.D, PhD.

The investigators will conduct a large study in the primary care clinic to determine the feasibility of using tethered capsule endomicroscopy as a screening method for Barrett's esophagus (BE) in the primary care practice environment. The investigators are also determining the prevalence of Barrett's esophagus in a primary care practice cohort at MGH.

The investigators have developed a tethered capsule OCT device intended as an inexpensive screening tool for BE. The capsule, which is attached to a thin, flexible tether, is reusable after being processed by a standard disinfection technique. Used without sedation, the capsule is swallowed by the participant and travels in the esophagus to the gastroesophageal junction (GEJ) via peristalsis. Cross-sectional microscopic OCT images of the entire esophagus are collected during transit. The total time needed for swallowing, imaging and retrieval does not exceed 10 minutes, with a total of 30 minutes for the procedure. The investigators have tested the feasibility and the tolerability of this new OCT screening technology in 250 procedures in healthy volunteers and patients with various esophageal diseases including BE. The procedure has been safe and well tolerated. High quality microscopic images of the esophagus have been obtained in 90% of the enrolled subjects.

Evaluation of Tethered Capsule Endomicroscopy as a Screening Tool for Barrett's Esophagus in the Primary Care Setting

The study team will ask the participant about their comfort level throughout the procedure. Participants will be asked to score the tolerability of the procedure using a scoring system from 0-10. 0= the least tolerable, 10= the most tolerable. The title of the scale is Subject Tolerability Questionnaire.

The PI will identify signs of Barrett's esophagus from the imaging data. This is a qualitative assessment performed by the PI, as this imaging technique is to novel to have standard quality grading.

Guillermo J. Tearney, MD, PhD, FACC, FCAP, FNAI

Subject will swallow the OFDI capsule and imaging will be acquired using the OFDI imaging system.

Imaging of Barrett's esophagus (BE) using OFDI capsule imaging

OFDI capsule imaging

The goal of this research is to determine the natural history of Barrett's esophagus (BE) using tethered capsule endomicroscopy (TCE) in patients undergoing surveillance endoscopy.

The MGH will be the first site in the multi-center study to begin enrolling. At the MGH 100 subjects with a previous diagnosis of Barrett's Esophagus (BE) will be enrolled.

Each subject will undergo a minimum of 2 esophagogastroduodenoscopies (EGD), one around the time of inclusion into the study and one at the end of the study, and 4 TCE imaging sessions (baseline, 1-year, 2-years and at the end of the 3-years follow-up). If it is determined by the treating physician that additional EGDs are needed, for extended follow-up or treatment, capsule imaging will be performed whenever possible.

Patients will have received written information prior to the day of the capsule procedure and patients will have another chance to discuss the procedure with the study coordinator and clinical study staff during the consent process prior to the capsule procedure. Participation in this study is completely voluntary, and the patient can stop the procedure at any time.

For each of the imaged patients, inclusion criteria and clinical characteristics such as age, sex, body mass index (BMI), current medication regimen, smoking history and GI related history will be recorded in the clinical form.

Subjects will be seated and asked to sip water to facilitate swallowing the capsule.

The device will be operated by experienced study staff trained in the procedure such as a registered nurse or one of the endoscopist co-investigators in this study. Emergency phone and/or pager contact of the collaborating GI clinician(s) will be provided. They will also be accessible during the procedure if any problems are encountered that require their expertise.

Imaging will be performed in the same manner as in our other current IRB approved tethered capsule endomicroscopy studies. The capsule position will be controlled manually via the tether outside of the subject's mouth by the catheter operator. Recorded real-time cross-sectional images displayed on the monitor and distance marks on the tether will be used for confirmation of capsule position in the esophagus. Images will be viewed in real time to determine when the capsule has reached the stomach. The resistance of the tether can also give information of the cardia position. Once in the stomach, the capsule will be gradually pulled back up through the esophagus to the mouth, also while imaging. The capsule may be repositioned for imaging up to 4 times up and 4 times down the esophagus. The subject may be asked to swallow a different size capsule (ranging from 5-12.8 mm in diameter and 20-30 cm in length) to obtain the best distal esophageal images. It is expected that the maximum experimental time including swallowing the capsule, the imaging procedure, and removal of the capsule will take approximately 10 minutes in total.

Natural History of Barrett's Esophagus Using Tethered Capsule Endomicroscopy

An investigator will assess the quality of the recorded images and movies obtained with each exam after imaging has been completed. They will assess how the images change over time.

Principal Investigator - MD, PhD, FACC, FCAP, FNAI

Imaging of the esophagus with a compact OFDI system and distal scanning catheter

Experimental OFDI Imaging

The goal of this research is to test a distal scanning capsule and a compact redesigned version of the OFDI imaging system in healthy and BE subjects to assess ease of use, safety and feasibility in preparation for its use in a multicenter clinical trial.

Ten healthy volunteer subjects and ten volunteers with a previous diagnosis of Barrett's Esophagus (BE) will be enrolled in the study.

The capsule is attached to a string-like tether which allows the operator to control as well as navigate the capsule as it progresses down the esophagus using peristalsis.

Images of the esophagus will be acquired in real time to be analyzed later.

Pilot Study for TCE Imaging of the Esophagus Using an OFDI Capsule With a Compact Imaging System

Pilot Study for TCE (Tethered Capsule Endomicroscopy) Imaging of the Esophagus Using an OFDI (Optical Frequency Domain Imaging) Capsule With a Compact Imaging System

Images obtained from the CIS will be assessed for quality and compared to images acquired from the previous imaging system

Professor of Pathology

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Esophagitis

Eosinophilic Esophagitis

Gastroenteritis

Eosinophilia

Leukocyte Disorders

Hematologic Diseases

Hypersensitivity

Hypersensitivity, Immediate

Eosinophilic Gastroenteritis

Subject will swallow the SECM capsule and the imaging of the esophagus will be performed using a SECM optical system

Subjects will swallow a SECM capsule and the SECM imaging will be performed

SECM capsule

Nitasha Bhat, MD

The goal of this validation study is to compare Spectrally Encoded Confocal Microscopy (SECM) Tethered Capsule Endoscopy (TCE) diagnosis of Eosinophilic Esophagitis to that of standard of care endoscopic biopsy.

Eosinophilic esophagitis is an inflammatory condition of the esophagus that occurs in response to certain foods or allergens. Approximately 300,000 people in the US have EoE, the incidence of newly diagnosed EoE is \~30,000/year, and EoE is found in 5-10% of all patients undergoing upper endoscopy. EoE is associated with debilitating symptoms, and is a common cause of dysphagia, strictures, and food impaction; it may even lead to esophageal perforation. Because of the impact of EoE on quality of life as well as the concern that this disease may progress to esophageal fibrosis with unknown long-term risks, experts recommend that EoE be treated until symptoms and eosinophilic infiltrate are resolved. Because the only objective method for diagnosing EoE is histopathologic assessment of multiple upper endoscopic biopsies, the processes of monitoring the esophagus during therapy and the food reintroduction involve a high number of repeat endoscopies. This process is both time consuming and frustrating for patients and their families. Because the endoscopic biopsy requires conscious sedation, it is also costly, exceeding $1000 per procedure. Given the rapid increase in the number of patients with this disease, there is a compelling need for a less invasive and more cost-effective means of identifying eosinophils in the esophagus.

Based on the extensive experience with Optical Coherence Tomography (OCT) and OFDI, the investigators at Tearney laboratory at MGH have developed a spectrally encoded confocal microscopy (SECM) technology that is able to acquire images at significantly higher frame rates than standard confocal microscopy. This SECM capability enables imaging of large portions of the esophagus at 2-µm resolution in realistic procedure times. Furthermore, the investigators at Tearney laboratory have created a tethered capsule SECM device that can be swallowed and used for EoE screening. The investigators at Tearney laboratory lab performed a pilot study using a SECM capsule on 58 subjects (2013-P-000863). The imaging was successful with no adverse or unanticipated events. SECM endoscopy capsule is similar to the approved endoscopy capsule.

A total of sixty (60) subjects will be recruited for this study. The imaging of the esophagus will be obtained. Subjects will not be sedated for the procedure.

The images obtained by the SECM capsule will be compared to the images obtained by the clinical endoscopy and biopsy. SECM imaging will be used for research purposes only and will not be used for diagnosis purposes.

Imaging of the Esophagus Using a SECM Capsule

comparing SECM imaging of the esophagus obtained with a SECM capsule to histopathology.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pilot Study for OCT Guided In Vivo Laser Capture Microdissection for Assessing the Prognosis of Barrett's Esophagus	NCT03830801	Barrett Esophag...	IVLCM tethered ...	18 Years -	Massachusetts General Hospital
Coordinating Center: Natural History of Barrett's Esophagus Using Tethered Capsule Endomicroscopy	NCT03459339	Barrett Esophag...	Tethered Capsul...	18 Years -	Massachusetts General Hospital
Evaluation of Tethered Capsule Endomicroscopy as a Screening Tool for Barrett's Esophagus in the Primary Care Setting	NCT04561791	Barrett Esophag... Barrett's Esoph... Barretts Esopha...	Tethered Capsul...	18 Years -	Massachusetts General Hospital
Natural History of Barrett's Esophagus Using Tethered Capsule Endomicroscopy	NCT02994693	Barrett Esophag... Barretts Esopha...	OFDI capsule im...	18 Years -	Massachusetts General Hospital
Pilot Study for OCT Guided In Vivo Laser Capture Microdissection for Assessing the Prognosis of Barrett's Esophagus	NCT03830801	Barrett Esophag...	IVLCM tethered ...	18 Years -	Massachusetts General Hospital
Coordinating Center: Natural History of Barrett's Esophagus Using Tethered Capsule Endomicroscopy	NCT03459339	Barrett Esophag...	Tethered Capsul...	18 Years -	Massachusetts General Hospital
Pilot Study for TCE Imaging of the Esophagus Using an OFDI Capsule With a Compact Imaging System	NCT02947971	Barrett's Esoph...	Experimental OF...	18 Years - 70 Years	Massachusetts General Hospital
Imaging of the Esophagus Using a SECM Capsule	NCT03546660	Eosinophilic Es... Barrett Esophag...	SECM capsule	12 Years -	Massachusetts General Hospital

Spots Global Cancer Trial Database for tethered capsule endomicroscopy