Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04519697
Other study ID # 20-936
Secondary ID
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date October 28, 2020
Est. completion date October 2022

Study information

Verified date April 2022
Source The Cleveland Clinic
Contact Allison Bayles, AA
Phone 216-444-0887
Email ibdstemcelltherapy@ccf.org
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Approximately 10% of all female Crohn's patients have a rectovaginal fistula. Rectovaginal fistulas cause air, stool, and/or drainage per vagina and may be associated with pain, recurrent urinary tract infections and diminished quality of life. Conventional therapy includes immunosuppressive medications used to treat Crohn's disease and various surgical interventions. However, all have limited ability to heal these fistulas. The purpose of this study is to determine the safety and efficacy of using allogeneic bone marrow derived mesenchymal stem cells (MSCs) to treat people with rectovaginal fistulas in the setting of Crohn's disease.


Description:

This study is designed to determine the safety and efficacy of direct injection of adult allogeneic bone marrow derived mesenchymal stem cells for the treatment of rectovaginal fistulas in the setting of Crohn's disease. The study will randomize 20 participants. Enrolled participants will be randomized to treatment group with MSCs versus placebo in a 3:1 fashion. Participants in the treatment group will have a direct injection of MSCs at a dose of 75 million cells. This will be given as a direct injection in and around the fistula tract. Participants will be evaluated for complete healing at three months. If complete healing has been achieved patients will continue to be followed for one year. If complete healing has not been achieved at three months, participants will be eligible for a second injection of MSCs at the same dose of 75 million cells. Control participants without complete healing from placebo will cross over at the six month visit to receive an injection of MSCs, and will be followed for one year after treatment for a total duration of 18 months.


Recruitment information / eligibility

Status Recruiting
Enrollment 40
Est. completion date October 2022
Est. primary completion date October 2022
Accepts healthy volunteers No
Gender Female
Age group 18 Years to 75 Years
Eligibility Inclusion Criteria: 1. Females 18-75 years of age with a diagnosis of Crohn's disease for at least six months duration. 2. Single-tract, rectovaginal fistula in the setting of Crohn's disease. 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, and ability to comply with protocol 6. 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 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 cancer including melanoma (with the exception of localized skin cancers) within one year of screening. 5. History of colorectal cancer within 5 years. 6. Investigational drug within 30 days of treatment 7. Pregnant or breast feeding or trying to become pregnant. 8. Presence of a rectovaginal or perineal body fistula 9. Change in Crohn's immunosuppressive regimen within the 2 months prior to enrollment 10. Uncontrolled intestinal Crohn's disease which will require escalation for medical therapy or surgery within 2 months of enrollment 11. Severe anal canal disease that is stenotic and requires dilation 12. Inability to wean corticosteroids 13. Unwilling to agree to use acceptable contraception methods during participation in study

Study Design


Intervention

Drug:
Mesenchymal Stem Cells
Adult allogeneic bone marrow derived mesenchymal stem cells for the treatment of rectovaginal fistulas in the setting of Crohn's disease.
Other:
Placebo
Normal Saline

Locations

Country Name City State
United States Cleveland Clinic Cleveland Ohio

Sponsors (1)

Lead Sponsor Collaborator
Amy Lightner

Country where clinical trial is conducted

United States, 

References & Publications (8)

García-Arranz M, Herreros MD, González-Gómez C, de la Quintana P, Guadalajara H, Georgiev-Hristov T, Trébol J, Garcia-Olmo D. Treatment of Crohn's-Related Rectovaginal Fistula With Allogeneic Expanded-Adipose Derived Stem Cells: A Phase I-IIa Clinical Trial. Stem Cells Transl Med. 2016 Nov;5(11):1441-1446. doi: 10.5966/sctm.2015-0356. Epub 2016 Jul 13. — View Citation

Hannaway CD, Hull TL. Current considerations in the management of rectovaginal fistula from Crohn's disease. Colorectal Dis. 2008 Oct;10(8):747-55; discussion 755-6. doi: 10.1111/j.1463-1318.2008.01552.x. Epub 2008 May 4. Review. — View Citation

Lightner AL, Dozois EJ, Dietz AB, Fletcher JG, Friton J, Butler G, Faubion WA. Matrix-Delivered Autologous Mesenchymal Stem Cell Therapy for Refractory Rectovaginal Crohn's Fistulas. Inflamm Bowel Dis. 2020 Apr 11;26(5):670-677. doi: 10.1093/ibd/izz215. — View Citation

Panés J, García-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. — View Citation

Panés J, García-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. — View Citation

Peyrin-Biroulet L, Loftus EV Jr, Colombel JF, Sandborn WJ. The natural history of adult Crohn's disease in population-based cohorts. Am J Gastroenterol. 2010 Feb;105(2):289-97. doi: 10.1038/ajg.2009.579. Epub 2009 Oct 27. Review. — View Citation

Sanz-Baro R, García-Arranz M, Guadalajara H, de la Quintana P, Herreros MD, García-Olmo D. First-in-Human Case Study: Pregnancy in Women With Crohn's Perianal Fistula Treated With Adipose-Derived Stem Cells: A Safety Study. Stem Cells Transl Med. 2015 Jun;4(6):598-602. doi: 10.5966/sctm.2014-0255. Epub 2015 Apr 29. — 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

Outcome

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 rectovaginal fistula in the setting of Crohn's disease as assessed by protocol CCF-Stem Cells IBD-003 Month 6
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 rectovaginal fistula 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 complete closure of the fistula tract upon assessment with an examination under anesthesia
Month 6, Month 12
Secondary Partial healing Number of participants with partial clinical healing post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of rectovaginal fistula in the setting of Crohn's disease
Partial 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 partial closure of the fistula tract upon assessment with an examination under anesthesia
Month 6, 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 rectovaginal fistula 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 6, Month 12
Secondary Worsening disease Number of participants with worsening disease post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of rectovaginal fistula 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 6, Month 12
See also
  Status Clinical Trial Phase
Active, not recruiting NCT04046913 - The ADDapt Diet in Reducing Crohn's Disease Inflammation N/A
Recruiting NCT05169593 - Prevention of Postoperative Endoscopic Recurrence With Endoscopy-driven Versus Systematic Biological Therapy Phase 4
Recruiting NCT06116604 - Early Bowel Resection for Terminal Ileal Crohn's Disease
Recruiting NCT05627128 - A Culturally Tailored Dietary Intervention to Treat Crohn's Disease N/A
Recruiting NCT05316584 - A Novel Remote Patient and Medication Monitoring Solution to Improve Adherence and PerSiStence With IBD Therapy N/A
Recruiting NCT05294107 - Intestinal Organoids N/A
Withdrawn NCT04349449 - ENTYVIO in Bio-naive Patients With Moderate/Severe Crohn's Disease (CD) in Daily Practice
Completed NCT05051943 - A Study of the Real-world Use of an Adalimumab Biosimilar and Evaluation of Nutritional Status on the Therapeutic Response
Completed NCT03058679 - Trial of Specific Carbohydrate and Mediterranean Diets to Induce Remission of Crohn's Disease N/A
Completed NCT02871635 - BI 695501 Versus Humira in Patients With Active Crohn's Disease: a Trial Comparing Efficacy, Endoscopic Improvement, Safety, and Immunogenicity Phase 3
Recruiting NCT04539665 - Extended Mesenteric Excision in Ileocolic Resections for Crohn's Disease. N/A
Recruiting NCT04266600 - Extended Mesenteric Excision in Ileocolic Resections for Crohn's Disease N/A
Recruiting NCT03913572 - Treatment of Perianal Disease Using Adipose-derived Stem Cells
Completed NCT03668249 - A Study to Characterize Multidimensional Model to Predict the Course of Crohn's Disease (CD)
Completed NCT03606499 - Real-world Effectiveness of Ustekinumab in Participants Suffering From Inflammatory Bowel Disease (Crohn's Disease or Ulcerative Colitis) With Extra-intestinal Manifestations or Immune-mediated Inflammatory Diseases
Terminated NCT04102111 - A Study Evaluating Participants With Moderately to Severely Active Crohn's Disease Phase 2
Recruiting NCT04997733 - Fecal Microbiota Transplantation in Crohn's Disease as Relay After Anti-TNF Withdrawal Phase 3
Recruiting NCT05906576 - Post-marketing Registry Study of Infliximab for Injection in Chinese Pediatric Crohn's Disease Patients Phase 4
Not yet recruiting NCT04502303 - 18F-FDG and 68Ga-FAPI PET/CT in Crohn's Disease Phase 2
Not yet recruiting NCT04398836 - Preoperative Nutrition for Crohn's Disease Patients Phase 3