Mesenchymal Stem Cells for the Treatment of Rectovaginal Fistulas in Participants With Crohn's Disease

NCT ID: NCT04519697

Last Updated: 2022-04-05

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-28
• Study Completion Date: 2022-10-31

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.

Conditions

Rectovaginal Fistula; Crohn Disease; Crohn Disease of Vulva; Rectolabial; Fistula

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Mesenchymal Stem Cells

Intervention Type: DRUG

Adult allogeneic bone marrow derived mesenchymal stem cells for the treatment of rectovaginal fistulas in the setting of Crohn's disease.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Normal Saline

Interventions

Mesenchymal Stem Cells

Adult allogeneic bone marrow derived mesenchymal stem cells for the treatment of rectovaginal fistulas in the setting of Crohn's disease.

Intervention Type: DRUG

Placebo

Normal Saline

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Amy Lightner

OTHER

Sponsor Role: lead

Responsible Party

Amy Lightner

Sponsor-investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Amy Lightner, MD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

Cleveland Clinic

Cleveland, Ohio, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Allison Bayles, AA

Role: CONTACT

ibdstemcelltherapy@ccf.org

216-444-0887

Alex VanDenBossche, BSN

Role: CONTACT

ibdstemcelltherapy@ccf.org

216-379-0307

Facility Contacts

Allison Bayles

Role: primary

Alex VanDenBossche

Role: backup

References

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Reference Type: BACKGROUND

PMID: 19861953 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11910338 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18462243 (View on PubMed)

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Reference Type: BACKGROUND

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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.

Reference Type: BACKGROUND

PMID: 29277560 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31605115 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27412883 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25925838 (View on PubMed)

Other Identifiers

20-936

Identifier Type: -

Identifier Source: org_study_id