Mesenchymal Stem Cells for the Treatment of Pouch Fistulas in Crohn's

NCT04073472 | Withdrawn Phase 1 DMC FDA Drug

• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to determine the safety and feasibility of using allogeneic bone marrow derived mesenchymal stem cells (MSCs) to treat people with an ileal pouch anal anastomosis (IPAA) who develop a fistula in the setting of Crohn's disease of the pouch.

Conditions

Crohn's Disease; Fistula; Anal Fistula; Pouch, Ileal; Pouches, Ileoanal

Keywords

crohn disease; mesenchymal stem cells; pouch fistulas

Outcome Measures

Primary Outcomes (1)

• Safety and Feasibility: Number Of Adverse Events

  Evaluate the number of adverse event occurring during the trial (including clinically significant changes in physical examination, radiographic images, safety lab tests, vital signs).

  Baseline, Drug administration Visit, Day 1, 1 week, 2 weeks, 1 month, 2 months, 3 month, 6 month, 12 month after each MSCs injection

Secondary Outcomes (2)

• Radiographic Healing

  Baseline, 1 week, 2 weeks, 1 month, 2 months, 3 month, 6 month, 12 month after each 100% cessation of drainage on both clinical exam with deep palpation and per patient MSCs injection

• Clinical Healing

  Baseline, 1 week, 2 weeks, 1 month, 2 months, 3 month, 6 month, 12 month after each 100% cessation of drainage on both clinical exam with deep palpation and per patient MSCs injection

Other Outcomes (1)

• Alloimmune response to mesenchymal stem cells

  Baseline, 1 week, 3 months 12 months after each MSCs injection

Study Arms (1)

mesenchymal stem cells (MSCs)

EXPERIMENTAL

Direct injection of 75 million allogeneic bone marrow derived mesenchymal stem cells (MSC) into ileal pouch fistula at baseline and possibly again after 3 months if not completely healed.

Drug: mesenchymal stem cells (MSCs)

Interventions

mesenchymal stem cells (MSCs) DRUG

Allogeneic bone marrow derived mesenchymal stem cells (MSCs) direct injection to an ileal pouch fistula in the setting of Crohn's disease of the pouch

Also known as: Allogeneic Bone Marrow Derived Mesenchymal Stem Cells

mesenchymal stem cells (MSCs)

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 (\>3 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 3 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 patient.
• HIV
• Hepatitis B or C
• Abnormal CBC at screening
• Abnormal AST or ALT at screening
• History of cancer including melanoma (with the exception of localized skin cancers)
• 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,
• Patients with greater than 3 blind/branching tracts are excluded
• Fistula tracts on the left and/or right side are allowed

Sponsors & Collaborators

• The Cleveland Clinic: lead

Related Publications (11)

• Garcia-Olmo D, Garcia-Arranz M, Garcia LG, Cuellar ES, Blanco IF, Prianes LA, Montes JA, Pinto FL, Marcos DH, Garcia-Sancho L. Autologous stem cell transplantation for treatment of rectovaginal fistula in perianal Crohn's disease: a new cell-based therapy. Int J Colorectal Dis. 2003 Sep;18(5):451-4. doi: 10.1007/s00384-003-0490-3. Epub 2003 May 20.

  PMID: 12756590 BACKGROUND

• Cho YB, Lee WY, Park KJ, Kim M, Yoo HW, Yu CS. Autologous adipose tissue-derived stem cells for the treatment of Crohn's fistula: a phase I clinical study. Cell Transplant. 2013;22(2):279-85. doi: 10.3727/096368912X656045. Epub 2012 Sep 21.

  PMID: 23006344 BACKGROUND

• Dietz AB, Dozois EJ, Fletcher JG, Butler GW, Radel D, Lightner AL, Dave M, Friton J, Nair A, Camilleri ET, Dudakovic A, van Wijnen AJ, Faubion WA. Autologous Mesenchymal Stem Cells, Applied in a Bioabsorbable Matrix, for Treatment of Perianal Fistulas in Patients With Crohn's Disease. Gastroenterology. 2017 Jul;153(1):59-62.e2. doi: 10.1053/j.gastro.2017.04.001. Epub 2017 Apr 9.

  PMID: 28400193 BACKGROUND

• Garcia-Olmo D, Garcia-Arranz M, Herreros D, Pascual I, Peiro C, Rodriguez-Montes JA. A phase I clinical trial of the treatment of Crohn's fistula by adipose mesenchymal stem cell transplantation. Dis Colon Rectum. 2005 Jul;48(7):1416-23. doi: 10.1007/s10350-005-0052-6.

  PMID: 15933795 BACKGROUND

• Garcia-Olmo D, Herreros D, Pascual I, Pascual JA, Del-Valle E, Zorrilla J, De-La-Quintana P, Garcia-Arranz M, Pascual M. Expanded adipose-derived stem cells for the treatment of complex perianal fistula: a phase II clinical trial. Dis Colon Rectum. 2009 Jan;52(1):79-86. doi: 10.1007/DCR.0b013e3181973487.

  PMID: 19273960 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

• Cho YB, Park KJ, Yoon SN, Song KH, Kim DS, Jung SH, Kim M, Jeong HY, Yu CS. Long-term results of adipose-derived stem cell therapy for the treatment of Crohn's fistula. Stem Cells Transl Med. 2015 May;4(5):532-7. doi: 10.5966/sctm.2014-0199. Epub 2015 Mar 31.

  PMID: 25829404 BACKGROUND

• Lee WY, Park KJ, Cho YB, Yoon SN, Song KH, Kim DS, Jung SH, Kim M, Yoo HW, Kim I, Ha H, Yu CS. Autologous adipose tissue-derived stem cells treatment demonstrated favorable and sustainable therapeutic effect for Crohn's fistula. Stem Cells. 2013 Nov;31(11):2575-81. doi: 10.1002/stem.1357.

  PMID: 23404825 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

• Ciccocioppo R, Bernardo ME, Sgarella A, Maccario R, Avanzini MA, Ubezio C, Minelli A, Alvisi C, Vanoli A, Calliada F, Dionigi P, Perotti C, Locatelli F, Corazza GR. Autologous bone marrow-derived mesenchymal stromal cells in the treatment of fistulising Crohn's disease. Gut. 2011 Jun;60(6):788-98. doi: 10.1136/gut.2010.214841. Epub 2011 Jan 21.

  PMID: 21257987 BACKGROUND

• de la Portilla F, Alba F, Garcia-Olmo D, Herrerias JM, Gonzalez FX, Galindo A. Expanded allogeneic adipose-derived stem cells (eASCs) for the treatment of complex perianal fistula in Crohn's disease: results from a multicenter phase I/IIa clinical trial. Int J Colorectal Dis. 2013 Mar;28(3):313-23. doi: 10.1007/s00384-012-1581-9. Epub 2012 Sep 29.

  PMID: 23053677 BACKGROUND

MeSH Terms

Conditions

Crohn Disease; Fistula; Rectal Fistula

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Intestinal Fistula; Digestive System Fistula; Rectal Diseases

Study Officials

• Amy Lightner, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Surgeon

Study Record Dates

• First Submitted: August 23, 2019
• First Posted: August 29, 2019
• Study Start: June 1, 2021
• Primary Completion: June 1, 2022
• Study Completion: June 1, 2023
• Last Updated: April 15, 2026

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share