Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04519684
Recruitment Status : Recruiting
First Posted : August 20, 2020
Last Update Posted : March 19, 2021
Sponsor:
Information provided by (Responsible Party):
Amy Lightner, The Cleveland Clinic

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Ileal Pouch Crohn Disease Drug: Mesenchymal stem cells Other: Placebo Phase 1 Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Masking Description: Single
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : October 28, 2020
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : October 2022

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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


  2. 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


  3. 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


  4. 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




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 (>3 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 3 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 patient.
  6. Specific exclusions;

    1. HIV
    2. Hepatitis B or C
    3. Abnormal CBC at screening
    4. Abnormal AST or ALT at screening
  7. History of cancer including melanoma (with the exception of localized skin cancers)
  8. Investigational drug within thirty (30) days of baseline
  9. Pregnant or breast feeding or trying to become pregnant
  10. Branching fistula tract that has > 2 internal openings or 3 external openings,

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04519684


Contacts
Layout table for location contacts
Contact: Kavita Elliott, BS 216-403-3573 ibdstemcelltherapy@ccf.org
Contact: Caroline Matyas, BS 216-212-0746 ibdstemcelltherapy@ccf.org

Locations
Layout table for location information
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Kavita Elliott         
Sponsors and Collaborators
Amy Lightner
Investigators
Layout table for investigator information
Principal Investigator: Amy Lightner, MD The Cleveland Clinic
Publications:

Layout table for additonal information
Responsible Party: Amy Lightner, Sponsor-investigator, The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT04519684    
Other Study ID Numbers: CCF-Stem Cells IBD-002
First Posted: August 20, 2020    Key Record Dates
Last Update Posted: March 19, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Crohn Disease
Fistula
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Pathological Conditions, Anatomical