Micro-Layer Ablation of Barrett's Metaplasia- A Two-Phase, Multi-Center Trial - Extension of Follow-up to 5 Years (AIM)

This study was conducted in 2 serial phases (dosimetry phase and effectiveness phase) to evaluate a balloon-based ablation device (HALO360) that delivers a pre-set amount of energy density (J/cm2) to barrett's tissue. The dosimetry phase evaluated the dose-response and the safety of delivering 6 to 12 J/cm2. The effectiveness phase used 10 J/cm2 delivered twice for all patients, followed by Esophagogastroduodenoscopy (EGD) with biopsies at 1, 3, 6, and 12 months. A second ablation procedure was performed if Barretts esophagus (BE) was present at 1 or 3 months. A complete response (CR) was defined as all biopsy specimens negative for Barrett's Esophagus at 12 months. The effectiveness phase of the present study was extended to a 2.5-year follow-up. This trial incorporated an opportunity for persistent BE to be treated with a focal ablation device (HALO90), achieving a CR in 98.4% of patients by the 2.5-year follow-up,the results of which were published . There is ample evidence that RadioFrequency Ablation (RFA) for Barrett's esophagus is effective and safe. Having additional follow-up (5 years) would add valuable information to the literature, thus aiding the physician in making patient management decisions about the appropriate follow-up interval after RFA.

Study Overview

• Status: Completed
• Conditions: Barrett Esophagus
• Intervention / Treatment: Device: HALO Ablation System

Detailed Description

This study is intended to gather additional information regarding the performance of a bipolar balloon electrode device (HALO360) utilizing radiofrequency (RF) energy in the micro-layer ablation of Barrett's esophagus, a precancerous, metaplastic change in the esophageal lining. The device has received 510(k) clearance for specific indications, including the treatment of Barrett's esophagus.

This study is conducted in two phases and is intended to further evaluate the effect of micro-layer ablation of Barrett's metaplasia using a 510(k) cleared, bipolar, balloon electrode device. Phase I (n=30) is intended to provide additional information regarding the effects of three randomized treatment parameters (energy settings, Joules/cm2). Phase II (n=70) is intended to provide additional information regarding the effects of the optimal technique and energy density settings (Joules/cm2) determined from the 1-month endoscopy results of Phase I. Phase 2 primary endpoint was histological clearance of Barrett's (% patients). This trial incorporated an opportunity for persistent BE to be treated with a focal ablation device (HALO90), at the 2.5-year follow-up, achieving a CR in 98.4% of patients. Having additional follow-up (5 years) would add valuable information to the literature, thus aiding the physician in making patient management decisions about the appropriate follow-up interval after RFA. This study will allow collection of 5-year follow-up biopsies and, thereafter, offer RFA for any subject with persistent Barrett's.

Upon approval of the present amendment to the protocol (B-200-5 year extension) and the informed consent form (ICF) at each study site, subjects who participated in B-200-2.5 year extension and had a biopsy at 2.5 years after initial enrollment will be offered participation in this extension.

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Puerto Rico
  • Ponce, Puerto Rico, 00717
    • Ponce Gastroenterology Research
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Scottsdale
  • California
    • Orange, California, United States, 92868
      • UC Irvine Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Sciences University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • UNIVERSITY of PENNSYLVANIA
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • Gastrointestinal Associates
  • Washington
    • Seattle, Washington, United States, 98405
      • Tacoma Digestive Disease and Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject has documented histopathological diagnosis of Barrett's metaplasia (without dysplasia) as follows:

   • biopsies obtained less than 6 months prior to enrollment, and
   • biopsies obtained and reviewed at the investigator institution, and
   • biopsy protocol included at least 4 quadrant biopsies per 2 cm length of Barrett's metaplasia

2. Barrett metaplasia endoscopic length:

   Phase I : 2-3 cm Barrett's length (inclusive) Phase II: 2-6 cm Barrett's length (inclusive)

3. Age 18-75 years inclusive
4. Subject agrees to participate, fully understands content of informed consent form, and signs the informed consent form
5. Five year extension: All subjects who participated in B-200-2.5 year extension and had a biopsy at 2.5 years after initial enrollment (n=61) will be offered participation in this extension.

Exclusion Criteria:

1. Subjects is pregnant or planning a pregnancy
2. Esophageal stricture preventing passage of endoscope or catheter
3. Active esophagitis (Hetzel-Dent Grade III or IV) described as erosions or ulcerations encompassing more than 10% of distal esophagus
4. Barrett's metaplasia with dysplasia (any previous biopsy)
5. History or current diagnosis of malignancy of the esophagus
6. Prior radiation therapy to the esophagus, except head and neck region radiation therapy
7. Any previous ablative therapy within the esophagus (photodynamic therapy, multipolar electrical coagulation, argon plasma coagulation, laser treatment, or other)
8. Any previous endoscopic mucosal resection within the esophagus
9. Any previous esophageal surgery, except fundoplication
10. Esophageal varices
11. Subject has an implantable pacing device (examples; AICD, neurostimulator, cardiac pacemaker) and has not received clearance for enrollment in this study by specialist responsible for the pacing device
12. Participation in another clinical study in past 60 days
13. Subject suffers from unstable psychiatric disorder(s)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Phase I: 6 J/cm2; Subjects randomized to the energy density group of 6 J/cm2 through the HALO Ablation System.	Device: HALO Ablation System; Phase I: 1-2 ablation visits; Phase II 1 to 12 months: 1-2 ablation visits; Phase II 12 to 30 months: 1-3 ablation visits Phase II 55-60 months: 0-1 ablation visit ******Phase I was a dosimetry study and Phase II used the preferred dose. The same intervention was used for each dose.; Other Names: HALO360; HALO90
ACTIVE_COMPARATOR: Phase I: 8 J/cm2; Subjects randomized to the energy density group of 8 J/cm2 through the HALO Ablation System.	Device: HALO Ablation System; Phase I: 1-2 ablation visits; Phase II 1 to 12 months: 1-2 ablation visits; Phase II 12 to 30 months: 1-3 ablation visits Phase II 55-60 months: 0-1 ablation visit ******Phase I was a dosimetry study and Phase II used the preferred dose. The same intervention was used for each dose.; Other Names: HALO360; HALO90
ACTIVE_COMPARATOR: Phase I: 10 J/cm2; Subjects randomized to the energy density group of 10 J/cm2 through the HALO Ablation System.	Device: HALO Ablation System; Phase I: 1-2 ablation visits; Phase II 1 to 12 months: 1-2 ablation visits; Phase II 12 to 30 months: 1-3 ablation visits Phase II 55-60 months: 0-1 ablation visit ******Phase I was a dosimetry study and Phase II used the preferred dose. The same intervention was used for each dose.; Other Names: HALO360; HALO90
ACTIVE_COMPARATOR: Phase I: 12 J/cm2; Subjects randomized to the energy density group of 12 J/cm2 through the HALO Ablation System.	Device: HALO Ablation System; Phase I: 1-2 ablation visits; Phase II 1 to 12 months: 1-2 ablation visits; Phase II 12 to 30 months: 1-3 ablation visits Phase II 55-60 months: 0-1 ablation visit ******Phase I was a dosimetry study and Phase II used the preferred dose. The same intervention was used for each dose.; Other Names: HALO360; HALO90
ACTIVE_COMPARATOR: Phase II; All Halo 360 treatments performed at 10 J/cm2 through the HALO Ablation System. All Halo 90 treatments performed at 12 J/cm2 through the HALO Ablation System.	Device: HALO Ablation System; Phase I: 1-2 ablation visits; Phase II 1 to 12 months: 1-2 ablation visits; Phase II 12 to 30 months: 1-3 ablation visits Phase II 55-60 months: 0-1 ablation visit ******Phase I was a dosimetry study and Phase II used the preferred dose. The same intervention was used for each dose.; Other Names: HALO360; HALO90

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Histological Clearance of Barrett's Metaplasia	The primary study outcomes were defined as the percent of patients with complete histological response to intestinal metaplasia (IM) (CR-IM). CR-IM means complete eradication of IM (diseased epithelium). A patient was considered a Complete Responder (CR) if all biopsies (100%) were negative for intestinal metaplasia (CR-IM).	5 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression of Histological Grade	Secondary outcomes of progression of histological grade was defined as proportion of participants who had progression of disease such as (i) prevalence of dysplasia; (ii) Kaplan-Meier CR-IM (Complete Response to Intestinal Metaplasia) survival analysis.	5 year
Adverse Events	The secondary outcome adverse events was defined as any event that occurred during the course of the trial	5 year
Percentage of Participants With Sub-squamous Intestinal Metaplasia	The secondary outcome sub-squamous intestinal metaplasia was defined as prevalence of buried glandular mucosa in the esophagus.	5 year

Collaborators and Investigators

• Sponsor: Covidien, GI Solutions
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: David E Fleischer, MD, Mayo Clinic

Publications and helpful links

General Publications

• Sharma VK, Wang KK, Overholt BF, Lightdale CJ, Fennerty MB, Dean PJ, Pleskow DK, Chuttani R, Reymunde A, Santiago N, Chang KJ, Kimmey MB, Fleischer DE. Balloon-based, circumferential, endoscopic radiofrequency ablation of Barrett's esophagus: 1-year follow-up of 100 patients. Gastrointest Endosc. 2007 Feb;65(2):185-95. doi: 10.1016/j.gie.2006.09.033.
• Fleischer DE, Overholt BF, Sharma VK, Reymunde A, Kimmey MB, Chuttani R, Chang KJ, Lightdale CJ, Santiago N, Pleskow DK, Dean PJ, Wang KK. Endoscopic ablation of Barrett's esophagus: a multicenter study with 2.5-year follow-up. Gastrointest Endosc. 2008 Nov;68(5):867-76. doi: 10.1016/j.gie.2008.03.008. Epub 2008 Jun 17.
• Fleischer DE, Overholt BF, Sharma VK, Reymunde A, Kimmey MB, Chuttani R, Chang KJ, Muthasamy R, Lightdale CJ, Santiago N, Pleskow DK, Dean PJ, Wang KK. Endoscopic radiofrequency ablation for Barrett's esophagus: 5-year outcomes from a prospective multicenter trial. Endoscopy. 2010 Oct;42(10):781-9. doi: 10.1055/s-0030-1255779. Epub 2010 Sep 20.

Study record dates

Study Major Dates

• Study Start: November 1, 2003
• Primary Completion (ACTUAL): February 1, 2007
• Study Completion (ACTUAL): October 1, 2009

Study Registration Dates

• First Submitted: June 19, 2007
• First Submitted That Met QC Criteria: June 20, 2007
• First Posted (ESTIMATE): June 21, 2007

Study Record Updates

• Last Update Posted (ACTUAL): March 13, 2017
• Last Update Submitted That Met QC Criteria: January 31, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Radiofrequency Ablation; Barrett's Esophagus; Intestinal Metaplasia
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Gastrointestinal Diseases; Esophageal Diseases; Precancerous Conditions; Barrett Esophagus; Metaplasia
• Other Study ID Numbers: B-200