S1270 Utilization of Chronic Cecal Distention to Induce a Colo-Gastric Brake Effect as a Potential Obesity Treatment: A Canine Feasibility Study

Abstract

Introduction: There is a need for novel obesity therapy. The “colo-gastric brake” is a known physiologic process in which cecal distention causes anorexia and delayed gastric/small bowel emptying. In this study we explored an innovative obesity approach, i.e. using cecal distention to trigger the colo-gastric brake, to induce anorexia and weight loss in a canine model. Methods: 3 dogs had daily food intake, weights and activity monitored for 2 weeks. The dogs underwent colonoscopy with placement of a novel self-expanding Nitinol stent (Biomerics, Park, MN), 8.5 cm diameter, and wall pressure 0.136 atm, into each cecum via the biopsy channel. Clips secured the stents. Stent location and expansion were imaged weekly for 4 weeks. Post-procedure, animals resumed their diet with activity and food intake measured daily; weights were taken weekly. High-caloric supplements were provided for excess weight loss. At day 90 animals underwent a 2nd colonoscopy; stents photographed and the animals sacrificed, tissues were harvested and gross/histologic analysis was performed. Results: Stents were deployed into each cecum with full radial expansion by 1 week, and no migration. Following implant, animals recovered well and exhibited normal behavior throughout the study with no adverse events. Water intake was normal throughout the study, but inappetence was noted immediately post-implant beginning on day 1 and persisted throughout the study. Food intake as a group decreased below 50% of baseline at the end of week 1, recovered to around 70% at week 3, then dropped precipitously to 25% of baseline from week 4 to the end of the study (p< 0.009). Severe weight loss by day 25 (15.8-20.6%) prompted high-caloric supplementation; some weight was regained after supplementation however there was still marked weight loss (11.2-16.1%; p< .015) at the end of 90 days. At necropsy, the cecal implants demonstrated full distention; histology showed a mixed chronic-active cellular response in the mucosa and mild fibrosis. Conclusion: Chronic cecal distention is feasible and appeared to trigger a colo-gastric brake effect in a canine model. Device implant was associated with normal activity, no complications, normal water intake, but immediate and persistent loss of appetite, with markedly decreased food intake and significant weight loss. Test devices maintained cecal position without tissue damage. Although a small animal trial, these results suggest that cecal distention may represent an option for obesity treatment.Figure 1.: Representative longitudinal radiographic images of the cecal implant devices. Left Image, Animal 1. A fractured implant wire is visible (arrow) in the image. Middle Image, Animal 2. A fractured implant wire is visible (arrow) in the image. Right Image, Animal 3. Implant wires appear intact. Note: The connector end orientation for animal 1 is opposite that of animals 2 and 3.