- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04519697
Mesenchymal Stem Cells for the Treatment of Rectovaginal Fistulas in Participants With Crohn's Disease (RVF)
A Phase IB/IIA Study of Adult Allogeneic Bone Marrow Derived Mesenchymal Stem Cells for the Treatment of Rectovaginal Fistulas in the Setting of Crohn's Disease.
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Allison Bayles, AA
- Phone Number: 216-444-0887
- Email: ibdstemcelltherapy@ccf.org
Study Contact Backup
- Name: Alex VanDenBossche, BSN
- Phone Number: 216-379-0307
- Email: ibdstemcelltherapy@ccf.org
Study Locations
-
-
Ohio
-
Cleveland, Ohio, United States, 44195
- Recruiting
- Cleveland Clinic
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Females 18-75 years of age with a diagnosis of Crohn's disease for at least six months duration.
- Single-tract, rectovaginal fistula in the setting of Crohn's disease.
- Have no contraindications to MR evaluations: e.g. pacemaker or magnetically active metal fragments, claustrophobia
- Ability to comply with protocol
- Competent and able to provide written informed consent, and ability to comply with protocol
- 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:
- Inability to give informed consent.
- 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.
Specific exclusions:
- Hepatitis B or C
- HIV
- 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 30 days of treatment
- Pregnant or breast feeding or trying to become pregnant.
- Presence of a rectovaginal or perineal body fistula
- Change in Crohn's immunosuppressive regimen within the 2 months prior to enrollment
- Uncontrolled intestinal Crohn's disease which will require escalation for medical therapy or surgery within 2 months of enrollment
- Severe anal canal disease that is stenotic and requires dilation
- Inability to wean corticosteroids
- Unwilling to agree to use acceptable contraception methods during participation in study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Mesenchymal Stem Cells
Direct injection of adult allogeneic bone marrow derived mesenchymal stem cells at a dose of 75 million cells into rectovaginal fistula at baseline with a possible repeat injection at 3 months if not completely healed from the first injection.
|
Adult allogeneic bone marrow derived mesenchymal stem cells for the treatment of rectovaginal fistulas in the setting of Crohn's disease.
|
Placebo Comparator: Placebo
Direct injection of normal saline with a possible repeat injection at 3 months if not completely healed from the first injection.
If not completely healed after 6 months, participants will then cross over to the treatment group to receive a direct injection of adult allogeneic bone marrow derived mesenchymal stem cells at a dose of 75 million cells into rectovaginal fistula.
|
Normal Saline
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Treatment related adverse events
Time Frame: Month 6
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Complete clinical healing
Time Frame: Month 6, Month 12
|
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
|
Partial healing
Time Frame: Month 6, Month 12
|
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
|
Lack of response
Time Frame: Month 6, Month 12
|
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
|
Worsening disease
Time Frame: Month 6, Month 12
|
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
|
Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- 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. doi: 10.1053/gast.2002.32362.
- 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.
- 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.
- 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.
- 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.
- 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.
- Garcia-Arranz M, Herreros MD, Gonzalez-Gomez C, de la Quintana P, Guadalajara H, Georgiev-Hristov T, Trebol 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.
- Sanz-Baro R, Garcia-Arranz M, Guadalajara H, de la Quintana P, Herreros MD, Garcia-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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Gastrointestinal Diseases
- Gastroenteritis
- Intestinal Diseases
- Pathological Conditions, Anatomical
- Rectal Diseases
- Inflammatory Bowel Diseases
- Vaginal Diseases
- Intestinal Fistula
- Digestive System Fistula
- Rectal Fistula
- Vaginal Fistula
- Fistula
- Crohn Disease
- Rectovaginal Fistula
Other Study ID Numbers
- 20-936
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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