Study of Mesenchymal Stem Cells for the Treatment of Ileal Pouch Fistula's in Participants With Crohn's Disease

NCT04519684 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 20-818
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Restorative proctocolectomy with ileal pouch anal anastomosis (IPAA) is the procedure of choice for patients with ulcerative colitis, familial adenomatous polyposis, and select patients with Crohn's disease due to overall low patient morbidity and good quality of life. However, some patients can develop Crohn's disease of the pouch, a clinical diagnosis of Crohn's disease following IPAA. One of the manifestations of Crohn's disease of the pouch includes a fistula from the pouch that travels to the vagina or perianal area. These fistulas can be quite difficult to manage with medications and local surgical intervention, and, on occasion result in a reconstruction pouch but more often require a pouch excision with permanent end ileostomy. The purpose of this study is to evaluate the safety and efficacy of using allogeneic bone marrow derived mesenchymal stem cells to treat people who have a peri-pouch fistula related to a clinical diagnosis of Crohn's disease of the pouch.

Conditions

Ileal Pouch; Crohn Disease

Outcome Measures

Primary Outcomes (1)

• Treatment related adverse events

  Number of participants with treatment related adverse events post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of medically refractory pouch fistulizing disease as assessed by protocol CCF-Stem Cells IBD-002

  Month 6

Secondary Outcomes (4)

• Complete clinical healing

  Month 6, Month 12

• Partial healing

  Month 6, Month 12

• Lack of response

  Month 6, Month 12

• Worsening disease

  Month 6, Month 12

Study Arms (2)

Mesenchymal stem cells

EXPERIMENTAL

Direct injection of allogeneic bone marrow derived mesenchymal stem cells at a dose of 75 million cells into the ileal pouch fistula(s) at baseline with a possible repeat injection at 3 months if not completely healed from the first injection.

Drug: Mesenchymal stem cells

Placebo

PLACEBO COMPARATOR

Direct injection of normal saline. If not completely healed after 6 months, participants will then cross over to the treatment group to receive a direct injection of allogeneic bone marrow derived mesenchymal stem cells at a dose of 75 million cells into ileal pouch fistula(s).

Other: Placebo

Interventions

Mesenchymal stem cells DRUG

Allogeneic bone marrow derived mesenchymal stem cells

Mesenchymal stem cells

Placebo OTHER

Normal Saline

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women 18-75 years of age who have undergone an ileal pouch anal anastomosis at least 6 months prior who have developed a clinical diagnosis of Crohn's disease of the pouch as determined by a combination of clinical symptoms, pouchoscopy with biopsy, enterography.
• Single and multi-tract (up to 2 internal and 3 external openings) fistula tract arising from the ileal pouch, ileal anal anastomosis, or anal canal distal to anastomosis that travels to the perianal skin, perineal body, or vagina. Patients with fistulas that arise from the pouch, anastomosis, or anal canal distal to the anastomosis will both be included in enrollment.
• Acceptable internal openings and tract locations for the fistula to arise from include the ileal pouch body, the pouch anal anastomosis, and the anal canal distal to the anastomosis.
• Acceptable external openings and tract locations for the fistula to arise from include the perianal skin, perineal body, and/or the vaginal wall.
• Concurrent Crohn's related therapies with stable doses (\>2 months) corticosteroids, 5-ASA drugs, immunomodulators, anti-TNF therapy, anti-integrin and anti-interleukin are permitted.
• Have failed conventional medical therapies described above, defined as a lack of response to systemic immune suppression (e.g. azathioprine, methotrexate, 6-mercaptopurine) or biologic (e.g. anti-TNF, anti-integrin, anti-interleukin) therapies to treat fistulizing CD for at least 2 months
• Have no contraindications to MR evaluations: e.g. pacemaker or magnetically active metal fragments, claustrophobia
• Competent and able to provide written informed consent
• Ability to comply with protocol.

You may not qualify if:

• Inability to give informed consent.
• Severe antibiotic refractory pouchitis
• Severe cuffitis refractory to antibiotics
• Change in medical management for CD in the previous 2 months or changes anticipated in the next 2 months
• Clinically significant medical conditions within the six months before administration of MSCs: e.g. myocardial infarction, active angina, congestive heart failure or other conditions that would, in the opinion of the investigators, compromise the safety of the subject.
• HIV
• Hepatitis B or C
• Abnormal CBC at screening
• i. Platelets \<50 kg/uL or greater than 1.5 million kg/uL ii. WBC \<50 x kg/uL iii. Hbg \<7.0 g/dL d. Abnormal AST or ALT at screening(defined as \>/= 2x ULN)
• History of cancer including melanoma (with the exception of localized skin cancers) within one year of screening
• History of colorectal cancer within 5 years
• Investigational drug within thirty (30) days of baseline
• Pregnant or breast feeding or trying to become pregnant
• Branching fistula tract that has \> 2 internal openings or 3 external openings,
• Subjects with greater than 3 blind/branching tracts are excluded

Sponsors & Collaborators

• Anthony Lembo: lead

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Related Publications (9)

• Fazio VW, Kiran RP, Remzi FH, Coffey JC, Heneghan HM, Kirat HT, Manilich E, Shen B, Martin ST. Ileal pouch anal anastomosis: analysis of outcome and quality of life in 3707 patients. Ann Surg. 2013 Apr;257(4):679-85. doi: 10.1097/SLA.0b013e31827d99a2.

  PMID: 23299522 BACKGROUND

• Ozdemir Y, Kiran RP, Erem HH, Aytac E, Gorgun E, Magnuson D, Remzi FH. Functional outcomes and complications after restorative proctocolectomy and ileal pouch anal anastomosis in the pediatric population. J Am Coll Surg. 2014 Mar;218(3):328-35. doi: 10.1016/j.jamcollsurg.2013.11.019. Epub 2013 Nov 26.

  PMID: 24468224 BACKGROUND

• Remzi FH, Fazio VW, Kirat HT, Wu JS, Lavery IC, Kiran RP. Repeat pouch surgery by the abdominal approach safely salvages failed ileal pelvic pouch. Dis Colon Rectum. 2009 Feb;52(2):198-204. doi: 10.1007/DCR.0b013e31819ad4b6.

  PMID: 19279412 BACKGROUND

• Belliveau P, Trudel J, Vasilevsky CA, Stein B, Gordon PH. Ileoanal anastomosis with reservoirs: complications and long-term results. Can J Surg. 1999 Oct;42(5):345-52.

  PMID: 10526518 BACKGROUND

• Foley EF, Schoetz DJ Jr, Roberts PL, Marcello PW, Murray JJ, Coller JA, Veidenheimer MC. Rediversion after ileal pouch-anal anastomosis. Causes of failures and predictors of subsequent pouch salvage. Dis Colon Rectum. 1995 Aug;38(8):793-8. doi: 10.1007/BF02049833.

  PMID: 7634973 BACKGROUND

• Molendijk I, Bonsing BA, Roelofs H, Peeters KC, Wasser MN, Dijkstra G, van der Woude CJ, Duijvestein M, Veenendaal RA, Zwaginga JJ, Verspaget HW, Fibbe WE, van der Meulen-de Jong AE, Hommes DW. Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells Promote Healing of Refractory Perianal Fistulas in Patients With Crohn's Disease. Gastroenterology. 2015 Oct;149(4):918-27.e6. doi: 10.1053/j.gastro.2015.06.014. Epub 2015 Jun 25.

  PMID: 26116801 BACKGROUND

• Panes J, Garcia-Olmo D, Van Assche G, Colombel JF, Reinisch W, Baumgart DC, Dignass A, Nachury M, Ferrante M, Kazemi-Shirazi L, Grimaud JC, de la Portilla F, Goldin E, Richard MP, Diez MC, Tagarro I, Leselbaum A, Danese S; ADMIRE CD Study Group Collaborators. Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease. Gastroenterology. 2018 Apr;154(5):1334-1342.e4. doi: 10.1053/j.gastro.2017.12.020. Epub 2017 Dec 24.

  PMID: 29277560 BACKGROUND

• Panes J, Garcia-Olmo D, Van Assche G, Colombel JF, Reinisch W, Baumgart DC, Dignass A, Nachury M, Ferrante M, Kazemi-Shirazi L, Grimaud JC, de la Portilla F, Goldin E, Richard MP, Leselbaum A, Danese S; ADMIRE CD Study Group Collaborators. Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn's disease: a phase 3 randomised, double-blind controlled trial. Lancet. 2016 Sep 24;388(10051):1281-90. doi: 10.1016/S0140-6736(16)31203-X. Epub 2016 Jul 29.

  PMID: 27477896 BACKGROUND

• Lightner AL, Reese J, Ream J, Nachand D, Jia X, Pineiro AO, Dadgar N, Steele S, Hull T. A Phase IB/IIA Study of Allogeneic, Bone Marrow-derived, Mesenchymal Stem Cells for the Treatment of Refractory Ileal-anal Anastomosis and Peripouch Fistulas in the Setting of Crohn's Disease of the Pouch. J Crohns Colitis. 2023 Apr 19;17(4):480-488. doi: 10.1093/ecco-jcc/jjac172.

  PMID: 36322714 DERIVED

MeSH Terms

Conditions

Crohn Disease

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Amy Lightner, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Single
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-investigator

Study Record Dates

• First Submitted: August 17, 2020
• First Posted: August 20, 2020
• Study Start: October 28, 2020
• Primary Completion: November 15, 2023
• Study Completion: November 15, 2023
• Last Updated: April 16, 2026

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)