A Phase I Study of Allogeneic Bone Marrow Derived Mesenchymal Stem Cells for the Treatment of Ileal Anal Anastomosis and Ileal Pouch Fistulas in the Setting of Crohn's Disease of the Pouch

Proctocolectomy with ileal pouch anal anastomosis (IPAA) remains the procedure of choice for patients with ulcerative colitis (UC). IPAA allows at risk tissue to be removed with restoration of intestinal continuity while maintaining favorable long-term functional outcomes and quality of life. While less than 30% of patients experience short-term postoperative morbidity following IPAA, up to 15% of pouches will ultimately fail due to technical or inflammatory complications, the majority of which manifest as a fistula from the pouch to the perianal or vaginal locations. Pouch failure due to a fistula tract is notoriously difficult to treat. Despite immunosuppressive medications and attempts at local repair, most patients will end up with a pouch excision and permanent ostomy. This can be a devastating outcome in some patients as it impacts body image and quality of life.

Pelvic sepsis following original IPAA has been reported in 5% to 25% of patients, and is the leading cause of pouch failure due to the development of pelvic fibrosis and decreased distensibility of the pouch, ultimately resulting in poor pouch function. One of the leading causes of pelvic sepsis and development of a pouch fistula is Crohn's Disease (CD) of the pouch. While the majority of pouches are constructed for UC, up to 25% of patients with an IPAA will end up having a change in diagnosis from UC to CD or development of de novo CD of the pouch.

The first report of successful healing of a Crohn's fistula with mesenchymal stem cells (MSCs) was in 2003. Since them great enthusiasm has spurred several phase I phase II, and phase III trials designed to study the safety and efficacy of MSCs for perianal CD, all of which have reported encouraging results with regard to safety and efficacy. With over 300 patients now treated, there is a large body of evidence supporting the local delivery of MSCs to heal perianal Crohn's fistulas. Peri-pouch fistulas are similar to Crohn's perianal fistulas except that instead of the rectum containing the internal opening of the fistula, the internal opening is in the ileal pouch, constructed in place of the rectum.

Given the high safety profile and relative success in treating perianal Crohn's disease with mesenchymal stem cells, the investigators are using a GMP grade allogeneic bone marrow derived MSC cell line to establish safety and secondarily monitor for healing in patients with ileal pouch fistulas in the setting of Crohn's disease of the pouch. This trial will use allogeneic bone marrow derived mesenchymal stem cells (MSCs) to produce regenerative signals. The specific rationale for MSCs in IPAA is based upon 1) their anti-inflammatory properties; 2) published experience of MSC in this condition and perianal Crohn's fistula demonstrating efficacy and safety; 3) existence of cGMP methods for their isolation and growth.

This study will enroll adult men and women who have undergone IPAA at least six months prior and now have a peri-pouch fistula related to Crohn's disease of the pouch. Patients who are refractory to conventional medical therapy will be considered. Patients enrolled will be those that meet current indications.