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

NCT04519697 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 20-936
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Crohn's disease; rectovaginal fistula; mesenchymal stem cells; mesenchymal stem cell

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Complete clinical healing

  Month 6, Month 12

• Partial healing

  Month 6, Month 12

• Lack of response

  Month 6, Month 12

• Worsening disease

  Month 6, Month 12

Study Arms (2)

Mesenchymal Stem Cells

EXPERIMENTAL

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.

Drug: Mesenchymal Stem Cells

Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

Interventions

Mesenchymal Stem Cells DRUG

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

Mesenchymal Stem Cells

Placebo OTHER

Normal Saline

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Anthony Lembo: lead

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Related Publications (8)

• 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.

  PMID: 19861953 BACKGROUND

• 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.

  PMID: 11910338 BACKGROUND

• 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.

  PMID: 18462243 BACKGROUND

• 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.

  PMID: 27477896 BACKGROUND

• 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.

  PMID: 29277560 BACKGROUND

• 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.

  PMID: 31605115 BACKGROUND

• 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.

  PMID: 27412883 BACKGROUND

• 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.

  PMID: 25925838 BACKGROUND

MeSH Terms

Conditions

Rectovaginal Fistula; Crohn Disease; Fistula

Condition Hierarchy (Ancestors)

Rectal Fistula; Intestinal Fistula; Digestive System Fistula; Digestive System Diseases; Intestinal Diseases; Gastrointestinal Diseases; Rectal Diseases; Vaginal Fistula; Vaginal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Inflammatory Bowel Diseases; Gastroenteritis

Study Officials

• Amy Lightner, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-investigator

Study Record Dates

• First Submitted: August 17, 2020
• First Posted: August 20, 2020
• Study Start: October 28, 2020
• Primary Completion: November 15, 2023
• Study Completion: November 15, 2023
• Last Updated: April 16, 2026

Record last verified: 2022-11

Locations

US (1)