Perianal Fistula Due to Crohn's Disease (Disorder) Clinical Trial
Official title:
A Phase I Study of Adult Allogeneic Bone Marrow Derived Mesenchymal Stem Cells for Pediatric Perianal Fistulizing Crohn's Disease
| NCT number | NCT04791878 |
| Other study ID # | 21-134 |
| Secondary ID | |
| Status | Recruiting |
| Phase | Phase 1 |
| First received | |
| Last updated | |
| Start date | April 1, 2021 |
| Est. completion date | April 1, 2023 |
This study plans to enroll 10 patients aged 13-17 years of age with refractory perianal fistulizing disease. Patients will be treated by direct injection to the fistula tract(s) with 75 million allogeneic bone marrow derived mesenchymal stem cells at baseline and again after 3 months if not completely healed.
| Status | Recruiting |
| Enrollment | 10 |
| Est. completion date | April 1, 2023 |
| Est. primary completion date | April 1, 2023 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 13 Years to 17 Years |
| Eligibility | Inclusion Criteria 1. Males and females aged 13-17 with a diagnosis of Crohn's disease for at least six months duration. 2. Single and Multi-tract Perianal fistula, with or without previous failed surgical repair. 3. Have no contraindications to MR evaluations: e.g. pacemaker or magnetically active metal fragments, claustrophobia 4. Ability to comply with protocol 5. Competent and able to provide written informed consent 6. Concurrent Crohn's-related therapies with stable doses corticosteroids, 5- ASA drugs, immunomodulators, anti-TNF therapy, anti-integrin and anti-interleukin therapies are permitted. 7. Agree to use birth control or abstinence to avoid pregnancy during the study Exclusion Criteria 1. Inability to give informed consent. 2. 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. 3. Specific exclusions: 1. Hepatitis B or C 2. HIV 3. Abnormal AST or ALT at screening (defined as >/+2x ULN) 4. History of colon cancer in the past two years, or treatment for other cancers within the last 6 months. 5. Investigational drug within one month of treatment 6. Pregnant or breast feeding or trying to become pregnant. 7. Presence of a rectovaginal or perineal body fistula 8. Change in Crohn's immunosuppressive regimen within the 2 months prior to enrollment 9. Uncontrolled intestinal Crohn's disease which will require escalation for medical therapy or surgery within 2 months of enrollment 10. Severe anal canal disease that is stenotic and requires dilation 11. Female participant unwilling to agree to use acceptable contraception methods during participation in study |
| Country | Name | City | State |
|---|---|---|---|
| United States | Cleveland Clinic | Cleveland | Ohio |
| Lead Sponsor | Collaborator |
|---|---|
| Amy Lightner |
United States,
Adler J, Dong S, Eder SJ, Dombkowski KJ; ImproveCareNow Pediatric IBD Learning Health System. Perianal Crohn Disease in a Large Multicenter Pediatric Collaborative. J Pediatr Gastroenterol Nutr. 2017 May;64(5):e117-e124. doi: 10.1097/MPG.0000000000001447. — View Citation
Aguilera-Castro L, Ferre-Aracil C, Garcia-Garcia-de-Paredes A, Rodriguez-de-Santiago E, Lopez-Sanroman A. Management of complex perianal Crohn's disease. Ann Gastroenterol. 2017;30(1):33-44. doi: 10.20524/aog.2016.0099. Epub 2016 Oct 27. Review. — View Citation
Chaparro M, Zanotti C, Burgueño P, Vera I, Bermejo F, Marín-Jiménez I, Yela C, López P, Martín MD, Taxonera C, Botella B, Pajares R, Ponferrada A, Calvo M, Algaba A, Pérez L, Casis B, Maté J, Orofino J, Lara N, García-Losa M, Badia X, Gisbert JP. Health care costs of complex perianal fistula in Crohn's disease. Dig Dis Sci. 2013 Dec;58(12):3400-6. doi: 10.1007/s10620-013-2830-7. Epub 2013 Sep 13. — View Citation
Hellers G, Bergstrand O, Ewerth S, Holmström B. Occurrence and outcome after primary treatment of anal fistulae in Crohn's disease. Gut. 1980 Jun;21(6):525-7. — View Citation
Kappelman MD, Moore KR, Allen JK, Cook SF. Recent trends in the prevalence of Crohn's disease and ulcerative colitis in a commercially insured US population. Dig Dis Sci. 2013 Feb;58(2):519-25. doi: 10.1007/s10620-012-2371-5. Epub 2012 Aug 29. — View Citation
Kasparek MS, Glatzle J, Temeltcheva T, Mueller MH, Koenigsrainer A, Kreis ME. Long-term quality of life in patients with Crohn's disease and perianal fistulas: influence of fecal diversion. Dis Colon Rectum. 2007 Dec;50(12):2067-74. — View Citation
Kugathasan S, Judd RH, Hoffmann RG, Heikenen J, Telega G, Khan F, Weisdorf-Schindele S, San Pablo W Jr, Perrault J, Park R, Yaffe M, Brown C, Rivera-Bennett MT, Halabi I, Martinez A, Blank E, Werlin SL, Rudolph CD, Binion DG; Wisconsin Pediatric Inflammatory Bowel Disease Alliance. Epidemiologic and clinical characteristics of children with newly diagnosed inflammatory bowel disease in Wisconsin: a statewide population-based study. J Pediatr. 2003 Oct;143(4):525-31. — View Citation
Markowitz J, Grancher K, Rosa J, Simpser E, Aiges H, Daum F. Highly destructive perianal disease in children with Crohn's disease. J Pediatr Gastroenterol Nutr. 1995 Aug;21(2):149-53. — View Citation
Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, Benchimol EI, Panaccione R, Ghosh S, Barkema HW, Kaplan GG. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012 Jan;142(1):46-54.e42; quiz e30. doi: 10.1053/j.gastro.2011.10.001. Epub 2011 Oct 14. Review. — View Citation
Sandborn WJ, Fazio VW, Feagan BG, Hanauer SB; American Gastroenterological Association Clinical Practice Committee. AGA technical review on perianal Crohn's disease. Gastroenterology. 2003 Nov;125(5):1508-30. Review. — View Citation
Schwartz DA, Loftus EV Jr, Tremaine WJ, Panaccione R, Harmsen WS, Zinsmeister AR, Sandborn WJ. The natural history of fistulizing Crohn's disease in Olmsted County, Minnesota. Gastroenterology. 2002 Apr;122(4):875-80. — View Citation
Vernier-Massouille G, Balde M, Salleron J, Turck D, Dupas JL, Mouterde O, Merle V, Salomez JL, Branche J, Marti R, Lerebours E, Cortot A, Gower-Rousseau C, Colombel JF. Natural history of pediatric Crohn's disease: a population-based cohort study. Gastroenterology. 2008 Oct;135(4):1106-13. doi: 10.1053/j.gastro.2008.06.079. Epub 2008 Jul 3. — View Citation
* Note: There are 12 references in all — Click here to view all references
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 perianal fistula(s) in the setting of Crohn's disease as assessed by protocol | Month 3 | |
| Primary | 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 perianal fistula(s) in the setting of Crohn's disease as assessed by protocol | Month 12 | |
| Secondary | Complete clinical healing | Number of participants with complete clinical healing post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease.
Complete Healing is defined as: Radiographic Healing: MRI with an absence of a fluid collection >2 cm in 3 of 3 dimensions, lack of edema, inflammation or sign of active inflammatory response. A remnant scar of a fistula tract may remain Clinical Healing: 100% cessation of drainage on both clinical exam with deep palpation and per patient report and epithelization of the external fistula opening |
Month 3 | |
| Secondary | Complete clinical healing | Number of participants with complete clinical healing post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease.
Complete Healing is defined as: Radiographic Healing: MRI with an absence of a fluid collection >2 cm in 3 of 3 dimensions, lack of edema, inflammation or sign of active inflammatory response. A remnant scar of a fistula tract may remain Clinical Healing: 100% cessation of drainage on both clinical exam with deep palpation and per patient report and epithelization of the external fistula opening |
Month 12 | |
| Secondary | Partial clinical healing | Number of participants with partial clinical healing post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease
Partial clinical healing is defined as: Radiographic Healing: MRI with an absence of a fluid collection >2 cm in 2 of 3 dimensions, lack of edema, inflammation or sign of active inflammatory response. A remnant scar of a fistula tract may remain Clinical healing: Greater than or equal to 50 % cessation of drainage on both clinical exam with deep palpation and per patient report and epithelization of the external fistula opening |
Month 3 | |
| Secondary | Partial clinical healing | Number of participants with partial clinical healing post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease
Partial clinical healing is defined as: Radiographic Healing: MRI with an absence of a fluid collection >2 cm in 2 of 3 dimensions, lack of edema, inflammation or sign of active inflammatory response. A remnant scar of a fistula tract may remain Clinical healing: Greater than or equal to 50 % cessation of drainage on both clinical exam with deep palpation and per patient report and epithelization of the external fistula opening |
Month 12 | |
| Secondary | Lack of response | Number of participants with lack of response post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease
Lack of response is defined as: Radiographic and Clinical healing which does not meet the threshold for Partial Healing |
Month 3 | |
| Secondary | Lack of response | Number of participants with lack of response post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease
Lack of response is defined as: Radiographic and Clinical healing which does not meet the threshold for Partial Healing |
Month 12 | |
| Secondary | Worsening of disease | Number of participants with worsening of disease post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease
Worsening disease is defined as: Radiographic: MRI with a fluid collection >2 cm in 2 of 3 dimensions, edema, inflammation or sign of active inflammatory response. An increased number of tracts may be seen, or increased branching from the primary tract, Clinical: Increased drainage per patient report and on clinical exam |
Month 3 | |
| Secondary | Worsening of disease | Number of participants with worsening of disease post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease
Worsening disease is defined as: Radiographic: MRI with a fluid collection >2 cm in 2 of 3 dimensions, edema, inflammation or sign of active inflammatory response. An increased number of tracts may be seen, or increased branching from the primary tract, Clinical: Increased drainage per patient report and on clinical exam |
Month 12 |