Ablation of Intestinal Metaplasia Containing Dysplasia
Condition: Barrett Esophagus
MeSH terms: Barrett Esophagus; Metaplasia
Study type: Interventional

Summary: 
      The purpose of this study is to determine if the intervention of a 510(k)-cleared
      endoscopically-guided (Halo Ablation systems), ablation system plus anti-secretory therapy is
      better than anti-secretory therapy alone in clearing Barrett's Esophagus.
    

Detailed description: 
      Barrett's esophagus or intestinal metaplasia (IM) is a change in the epithelial lining of the
      esophagus. Barrett's esophagus develops as a result of chronic exposure of the esophagus to
      refluxed stomach acid and enzymes, as well as bile, resulting in recurrent mucosal injury.
      Injury is accompanied by inflammation and, ultimately, a cellular change (metaplasia) to a
      specialized columnar epithelium (Spechler SJ. Barrett's Esophagus. N Engl J Med
      2002;346(11):836-842.)

      Patients who have a diagnosis of Barrett's esophagus typically undergo surveillance endoscopy
      every 1-3 years with multiple biopsy specimens obtained to facilitate early detection of
      progression of IM to dysplasia (more severe precancerous changes) and adenocarcinoma.
      (Sampliner RE. Updated guidelines for the diagnosis, surveillance, and therapy of Barrett's
      esophagus. Am J Gastro 2002;97:1888-1895.) Progression of IM to low-grade dysplasia (LGD)
      indicates that cells exhibit more "cancer-like" architecture, thus warranting an accelerated
      surveillance endoscopy and biopsy program every 6 months rather than every 1-3 years as
      indicated for non-dysplastic IM. Progression to high-grade dysplasia (HGD) indicates that the
      cells are even more "cancer-like", thus warranting an even higher frequency surveillance
      endoscopy and biopsy program (every 3 months). Many HGD patients may undergo photodynamic
      therapy (PDT) or surgical esophagectomy, rather than remain in a frequent surveillance
      program. This more aggressive therapy is warranted because of the high rate of progression of
      HGD to adenocarcinoma.

      Esophageal adenocarcinoma most commonly occurs after an insidious progression from IM to LGD
      to HGD. Therefore, surveillance is increased upon diagnosis of worsening grades of dysplasia.
      The incidence of esophageal adenocarcinoma is rapidly increasing as middle-aged and elderly
      demographic sub-groups expand (Peters JH, Hagen JA, DeMeester SR. Barrett's Esophagus. J
      Gastrointest Surg 2004;8(1):1-17.) In 2004, the American Cancer Society reported that there
      were 14,250 new cases of esophageal cancer, and 13,300 deaths attributable to esophageal
      cancer (www.cancer.org). The U.S. National Cancer Institute Surveillance, Epidemiology and
      End Results Program reported that the increasing incidence of esophageal adenocarcinoma was
      greater than for any other cancer in the United States (www.cancer.gov).

      Elimination of the diseased epithelium containing IM with dysplasia is an intuitively
      favorable step for patients with this diagnosis. In other disease states, such as colon
      polyps or premalignant skin lesions, removal of the premalignant tissue results in a
      reduction in the risk of ultimately developing cancer. This is a logical conclusion when
      considering the premalignant lesion of Barrett's esophagus (particularly Barrett's esophagus
      with dysplasia), as the "tissue at risk" can be completely removed by ablation. This premise
      has been tested in the Barrett's dysplasia population in photoablative trials using PDT for
      patients with HGD, where PDT imparted a 50% reduction in risk over controls for the
      development of adenocarcinoma (Overholt BF, Panjehpour M, Haydek JM. Photodynamic therapy for
      Barrett's esophagus: follow-up. Gastrointest Endosc 1999;49(1):1-7.) The AIM Dysplasia Trial
      primary endpoints are removal of all dysplasia and IM, rather than detection of a difference
      in progression to adenocarcinoma or higher grades of dysplasia.
    

Intervention name(s): Ablation System plus anti-secretory medication; Sham procedure plus anti-secretory medication
Intervention type(s): Device; Device
Intervention description(s): Treatment group subjects undergo up to 4 ablation procedures (circumferential or focal) plus standard anti-secretory drug therapy (proton pump inhibitor, PPI).; The Sham Control group undergo an upper endoscopy procedure with sizing of the esophageal diameter (a component of the ablation procedure steps, deemed the sham procedure) plus standard anti-secretory drug therapy (Proton pump inhibitor, PPI)
Other intervention name(s): HALO 360; HALO 90
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Barrett's Esophagus; Dysplasia; Radiofrequency Ablation