Clinical trial NCT00489268: Micro-Layer Ablation of Barrett's Metaplasia- A Two-Phase, Multi-Center Trial - Extension of Follow-up to 5 Years
Official title: Micro-Layer Ablation of Barrett's Metaplasia- A Two-Phase, Multi-Center Trial - Extension of Follow-up to 5 Years
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Barrett Esophagus
Keywords: Barrett's Esophagus
Intestinal Metaplasia
Radiofrequency Ablation
Lead sponsor: Medtronic - MITG
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
First posted: 2007-06-21
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Percentage of Participants With Histological Clearance of Barrett's Metaplasia
timeFrame: 5 year
Secondary outcomes:
measure: Progression of Histological Grade
timeFrame: 5 year
measure: Adverse Events
timeFrame: 5 year
measure: Percentage of Participants With Sub-squamous Intestinal Metaplasia
timeFrame: 5 year
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Orange
country: United States
facility: UC Irvine Medical Center
state: California
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Knoxville
country: United States
facility: Gastrointestinal Associates
state: Tennessee
city: Seattle
country: United States
facility: Tacoma Digestive Disease and Research Center
state: Washington
city: Ponce
country: Puerto Rico
facility: Ponce Gastroenterology Research
Study officials:
affiliation: Mayo Clinic
name: David E Fleischer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.