Study of Mesenchymal Stem Cells for the Treatment of Ileal Pouch Fistula's in Participants With Crohn's Disease (IPAAF)

April 1, 2022 updated by: Amy Lightner

A Phase IB/IIA Study of Allogeneic Bone Marrow Derived Mesenchymal Stem Cells for the Treatment of Ileal Anal Anastomosis and Ileal Pouch Fistulas in the Setting of Crohn's Disease of the Pouch

Restorative proctocolectomy with ileal pouch anal anastomosis (IPAA) is the procedure of choice for patients with ulcerative colitis, familial adenomatous polyposis, and select patients with Crohn's disease due to overall low patient morbidity and good quality of life. However, some patients can develop Crohn's disease of the pouch, a clinical diagnosis of Crohn's disease following IPAA. One of the manifestations of Crohn's disease of the pouch includes a fistula from the pouch that travels to the vagina or perianal area. These fistulas can be quite difficult to manage with medications and local surgical intervention, and, on occasion result in a reconstruction pouch but more often require a pouch excision with permanent end ileostomy. The purpose of this study is to evaluate the safety and efficacy of using allogeneic bone marrow derived mesenchymal stem cells to treat people who have a peri-pouch fistula related to a clinical diagnosis of Crohn's disease of the pouch.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This aim of this study is to determine the safety and efficacy of adult allogeneic bone marrow derived mesenchymal stem cells (MSCs), for the treatment of medically refractory peri-pouch fistulizing disease in the setting of Crohn's disease of the pouch. 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 participants 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 6 month visit to receive an injection of MSCs and will be followed for one year after treatment to a total duration of 18 months. The primary efficacy analysis will be conducted at the month 6 time point.

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

  1. Men and women 18-75 years of age who have undergone an ileal pouch anal anastomosis at least 6 months prior who have developed a clinical diagnosis of Crohn's disease of the pouch as determined by a combination of clinical symptoms, pouchoscopy with biopsy, enterography.

  2. Single and multi-tract (up to 2 internal and 3 external openings) fistula tract arising from the ileal pouch, ileal anal anastomosis, or anal canal distal to anastomosis that travels to the perianal skin, perineal body, or vagina. Patients with fistulas that arise from the pouch, anastomosis, or anal canal distal to the anastomosis will both be included in enrollment.

    1. Acceptable internal openings and tract locations for the fistula to arise from include the ileal pouch body, the pouch anal anastomosis, and the anal canal distal to the anastomosis.
    2. Acceptable external openings and tract locations for the fistula to arise from include the perianal skin, perineal body, and/or the vaginal wall.
  3. 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.
  4. Have failed conventional medical therapies described above, defined as a lack of response to systemic immune suppression (e.g. azathioprine, methotrexate, 6-mercaptopurine) or biologic (e.g. anti-TNF, anti-integrin, anti-interleukin) therapies to treat fistulizing CD for at least 2 months
  5. Have no contraindications to MR evaluations: e.g. pacemaker or magnetically active metal fragments, claustrophobia
  6. Competent and able to provide written informed consent
  7. Ability to comply with protocol.

Exclusion Criteria

  1. Inability to give informed consent.
  2. Severe antibiotic refractory pouchitis
  3. Severe cuffitis refractory to antibiotics
  4. Change in medical management for CD in the previous 2 months or changes anticipated in the next 2 months
  5. 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.

  6. Specific exclusions;

    1. HIV
    2. Hepatitis B or C
    3. Abnormal CBC at screening

    i. Platelets <50 kg/uL or greater than 1.5 million kg/uL ii. WBC <50 x kg/uL iii. Hbg <7.0 g/dL d. Abnormal AST or ALT at screening(defined as >/= 2x ULN)

  7. History of cancer including melanoma (with the exception of localized skin cancers) within one year of screening
  8. History of colorectal cancer within 5 years
  9. Investigational drug within thirty (30) days of baseline
  10. Pregnant or breast feeding or trying to become pregnant

  11. Branching fistula tract that has > 2 internal openings or 3 external openings,

    1. Subjects with greater than 3 blind/branching tracts are excluded
    2. Fistula tracts on the left and/or right side are allowed
  12. Allergic to local anesthetics
  13. Unwilling to agree to use acceptable contraception methods during participation in study
  14. Subjects with a non-abscessed chronic cavity will not be included in enrollment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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 allogeneic bone marrow derived mesenchymal stem cells at a dose of 75 million cells into the ileal pouch fistula(s) at baseline with a possible repeat injection at 3 months if not completely healed from the first injection.
Drug: Mesenchymal stem cells
Allogeneic bone marrow derived mesenchymal stem cells
Placebo Comparator: Placebo
Direct injection of normal saline. If not completely healed after 6 months, participants will then cross over to the treatment group to receive a direct injection of allogeneic bone marrow derived mesenchymal stem cells at a dose of 75 million cells into ileal pouch fistula(s).
Other: Placebo
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 medically refractory pouch fistulizing disease as assessed by protocol CCF-Stem Cells IBD-002
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 medically refractory pouch fistulizing disease in the setting of Crohn's disease of the pouch.

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 epithelization of the external fistula opening
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 medically refractory pouch fistulizing disease 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 epithelization of the external fistula opening
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 medically refractory pouch fistulizing disease 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-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of medically refractory pouch fistulizing disease 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

This is where you will find people and organizations involved with this study.

Sponsor

Amy Lightner

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 28, 2020

Primary Completion (Anticipated)

October 1, 2022

Study Completion (Anticipated)

October 1, 2022

Study Registration Dates

First Submitted

August 17, 2020

First Submitted That Met QC Criteria

August 17, 2020

First Posted (Actual)

August 20, 2020

Study Record Updates

Last Update Posted (Actual)

April 5, 2022

Last Update Submitted That Met QC Criteria

April 1, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20-818

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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