Back to resultsMesenchymal Stem Cells for the Treatment of Rectovaginal Fistulas in Participants With Crohn's Disease (RVF)
Primary Purpose
Rectovaginal Fistula, Crohn Disease, Crohn Disease of Vulva
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Mesenchymal Stem Cells
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Rectovaginal Fistula focused on measuring Crohn's disease, rectovaginal fistula, mesenchymal stem cells, mesenchymal stem cell
Eligibility Criteria
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
Sites / Locations
- Cleveland ClinicRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Mesenchymal Stem Cells
Placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
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
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
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04519697
Brief Title
Mesenchymal Stem Cells for the Treatment of Rectovaginal Fistulas in Participants With Crohn's Disease
Acronym
RVF
Official Title
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 Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 28, 2020 (Actual)
Primary Completion Date
October 2022 (Anticipated)
Study Completion Date
October 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Amy Lightner
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectovaginal Fistula, Crohn Disease, Crohn Disease of Vulva, Rectolabial; Fistula
Keywords
Crohn's disease, rectovaginal fistula, mesenchymal stem cells, mesenchymal stem cell
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Masking
Participant
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Mesenchymal Stem Cells
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Mesenchymal Stem Cells
Intervention Description
Adult allogeneic bone marrow derived mesenchymal stem cells for the treatment of rectovaginal fistulas in the setting of Crohn's disease.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Normal Saline
Primary Outcome Measure Information:
Title
Treatment related adverse events
Description
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
Time Frame
Month 6
Secondary Outcome Measure Information:
Title
Complete clinical healing
Description
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
Time Frame
Month 6, Month 12
Title
Partial healing
Description
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
Time Frame
Month 6, Month 12
Title
Lack of response
Description
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
Time Frame
Month 6, Month 12
Title
Worsening disease
Description
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
Time Frame
Month 6, Month 12
10. Eligibility
Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Allison Bayles, AA
Phone
216-444-0887
Email
ibdstemcelltherapy@ccf.org
First Name & Middle Initial & Last Name or Official Title & Degree
Alex VanDenBossche, BSN
Phone
216-379-0307
Email
ibdstemcelltherapy@ccf.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amy Lightner, MD
Organizational Affiliation
The Cleveland Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Allison Bayles
First Name & Middle Initial & Last Name & Degree
Alex VanDenBossche
12. IPD Sharing Statement
Citations:
PubMed Identifier
19861953
Citation
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Results Reference
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PubMed Identifier
11910338
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. doi: 10.1053/gast.2002.32362.
Results Reference
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PubMed Identifier
18462243
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.
Results Reference
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PubMed Identifier
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Citation
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.
Results Reference
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PubMed Identifier
29277560
Citation
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.
Results Reference
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PubMed Identifier
31605115
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.
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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.
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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.
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Mesenchymal Stem Cells for the Treatment of Rectovaginal Fistulas in Participants With Crohn's Disease
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