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Mesenchymal Stem Cells for the Treatment of Pouch Fistulas in Crohn's (IPAAF)

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ClinicalTrials.gov Identifier: NCT04073472
Recruitment Status : Not yet recruiting
First Posted : August 29, 2019
Last Update Posted : August 29, 2019
Sponsor:
Information provided by (Responsible Party):
Amy Lightner, The Cleveland Clinic

Brief Summary:
The purpose of this study is to determine the safety and feasibility of using allogeneic bone marrow derived mesenchymal stem cells (MSCs) to treat people with an ileal pouch anal anastomosis (IPAA) who develop a fistula in the setting of Crohn's disease of the pouch.

Condition or disease Intervention/treatment Phase
Crohn's Disease Fistula Anal Fistula Pouch, Ileal Pouches, Ileoanal Drug: mesenchymal stem cells (MSCs) Phase 1

Detailed Description:

Proctocolectomy with ileal pouch anal anastomosis (IPAA) remains the procedure of choice for patients with ulcerative colitis (UC). IPAA allows at risk tissue to be removed with restoration of intestinal continuity while maintaining favorable long-term functional outcomes and quality of life. While less than 30% of patients experience short-term postoperative morbidity following IPAA, up to 15% of pouches will ultimately fail due to technical or inflammatory complications, the majority of which manifest as a fistula from the pouch to the perianal or vaginal locations. Pouch failure due to a fistula tract is notoriously difficult to treat. Despite immunosuppressive medications and attempts at local repair, most patients will end up with a pouch excision and permanent ostomy. This can be a devastating outcome in some patients as it impacts body image and quality of life.

Pelvic sepsis following original IPAA has been reported in 5% to 25% of patients, and is the leading cause of pouch failure due to the development of pelvic fibrosis and decreased distensibility of the pouch, ultimately resulting in poor pouch function. One of the leading causes of pelvic sepsis and development of a pouch fistula is Crohn's Disease (CD) of the pouch. While the majority of pouches are constructed for UC, up to 25% of patients with an IPAA will end up having a change in diagnosis from UC to CD or development of de novo CD of the pouch.

The first report of successful healing of a Crohn's fistula with mesenchymal stem cells (MSCs) was in 2003. Since them great enthusiasm has spurred several phase I phase II, and phase III trials designed to study the safety and efficacy of MSCs for perianal CD, all of which have reported encouraging results with regard to safety and efficacy. With over 300 patients now treated, there is a large body of evidence supporting the local delivery of MSCs to heal perianal Crohn's fistulas. Peri-pouch fistulas are similar to Crohn's perianal fistulas except that instead of the rectum containing the internal opening of the fistula, the internal opening is in the ileal pouch, constructed in place of the rectum.

Given the high safety profile and relative success in treating perianal Crohn's disease with mesenchymal stem cells, the investigators are using a GMP grade allogeneic bone marrow derived MSC cell line to establish safety and secondarily monitor for healing in patients with ileal pouch fistulas in the setting of Crohn's disease of the pouch. This trial will use allogeneic bone marrow derived mesenchymal stem cells (MSCs) to produce regenerative signals. The specific rationale for MSCs in IPAA is based upon 1) their anti-inflammatory properties; 2) published experience of MSC in this condition and perianal Crohn's fistula demonstrating efficacy and safety; 3) existence of cGMP methods for their isolation and growth.

This study will enroll adult men and women who have undergone IPAA at least six months prior and now have a peri-pouch fistula related to Crohn's disease of the pouch. Patients who are refractory to conventional medical therapy will be considered. Patients enrolled will be those that meet current indications.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I 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
Estimated Study Start Date : November 1, 2019
Estimated Primary Completion Date : November 1, 2021
Estimated Study Completion Date : November 1, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: mesenchymal stem cells (MSCs)
Direct injection of 60 million allogeneic bone marrow derived mesenchymal stem cells (MSC) into ileal pouch fistula at baseline and possibly again after 3 months if not completely healed.
Drug: mesenchymal stem cells (MSCs)
Allogeneic bone marrow derived mesenchymal stem cells (MSCs) direct injection to an ileal pouch fistula in the setting of Crohn's disease of the pouch
Other Name: Allogeneic Bone Marrow Derived Mesenchymal Stem Cells




Primary Outcome Measures :
  1. Safety and Feasibility: Number Of Adverse Events [ Time Frame: Baseline, Drug administration Visit, Day 1, 1 week, 2 weeks, 1 month, 2 months, 3 month, 6 month, 12 month after each MSCs injection ]
    Evaluate the number of adverse event occurring during the trial (including clinically significant changes in physical examination, radiographic images, safety lab tests, vital signs).


Secondary Outcome Measures :
  1. Radiographic Healing [ Time Frame: Baseline, 1 week, 2 weeks, 1 month, 2 months, 3 month, 6 month, 12 month after each 100% cessation of drainage on both clinical exam with deep palpation and per patient MSCs injection ]

    Number of Participants with:

    Complete 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

    Partial 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

    Partial Response MRI with an absence of a fluid collection >2 cm in 2 of 3 dimensions, lack of worsening inflammation or new tracts formed

    Lack of Response Radiographic healing which does not meet the threshold for Partial Response

    Decreased symptoms Greater than 50% reduction in drainage as reported by the patient at study visits.


  2. Clinical Healing [ Time Frame: Baseline, 1 week, 2 weeks, 1 month, 2 months, 3 month, 6 month, 12 month after each 100% cessation of drainage on both clinical exam with deep palpation and per patient MSCs injection ]

    Number of Participants with:

    Complete Healing 100% cessation of drainage on both clinical exam with deep palpation and per patient report and epithelization of the external fistula opening

    Partial 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

    Partial Response Less than 50% cessation of drainage on both clinical exam with deep palpation and per patient report and epithelization of the external fistula opening

    Lack of Response Clinical healing which does not meet the threshold for Partial Response

    Decreased symptoms Greater than 50% reduction in drainage as reported by the patient at study visits.



Other Outcome Measures:
  1. Alloimmune response to mesenchymal stem cells [ Time Frame: Baseline, 1 week, 3 months 12 months after each MSCs injection ]
    Measure HLA Class I & II SAB Antibody Screening - measures the presence (positive) or absence (negative) of antibodies



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.


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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 anal anastomosis or ileal pouch that travels to the perianal skin or perineal body, or vagina.
  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, and 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
  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, or has tract on both the right and left sides
  11. Allergic to local anesthetics
  12. Unwilling to agree to use acceptable contraception methods during participation in study

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): NCT04073472


Contacts
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Contact: Carmen Czich, RN BSN CCRP 216-442-4204 CZICH@ccf.org

Locations
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United States, Ohio
Cleveland Clinic Not yet recruiting
Cleveland, Ohio, United States, 44195
Contact: Carmen Czich, RN BSN CCRP    216-442-4204    CZICH@ccf.org   
Principal Investigator: Amy Lightner, MD         
Sub-Investigator: Benjamin Click, MD         
Sub-Investigator: Namita Gandhi, MD         
Sub-Investigator: Tracy Hull, MD         
Sub-Investigator: Douglas Nachand, MD         
Sub-Investigator: Miguel Regueiro, MD         
Sponsors and Collaborators
The Cleveland Clinic
Investigators
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Principal Investigator: Amy Lightner, MD The Cleveland Clinic

Publications:

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Responsible Party: Amy Lightner, Staff Surgeon, The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT04073472     History of Changes
Other Study ID Numbers: IPAAF IND# IRB# are pending
First Posted: August 29, 2019    Key Record Dates
Last Update Posted: August 29, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Amy Lightner, The Cleveland Clinic:
crohn disease
mesenchymal stem cells
pouch fistulas
Additional relevant MeSH terms:
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Crohn Disease
Rectal Fistula
Fistula
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Pathological Conditions, Anatomical
Intestinal Fistula
Digestive System Fistula
Rectal Diseases