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

Tracking Information
First Submitted Date  ICMJE August 23, 2019
First Posted Date  ICMJE August 29, 2019
Last Update Posted Date August 29, 2019
Estimated Study Start Date  ICMJE November 1, 2019
Estimated Primary Completion Date November 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 27, 2019)
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: August 27, 2019)
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: August 27, 2019)
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
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Mesenchymal Stem Cells for the Treatment of Pouch Fistulas in Crohn's
Official Title  ICMJE 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
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Crohn's Disease
  • Fistula
  • Anal Fistula
  • Pouch, Ileal
  • Pouches, Ileoanal
Intervention  ICMJE 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
Study Arms  ICMJE 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.
Intervention: Drug: mesenchymal stem cells (MSCs)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: August 27, 2019)
15
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 1, 2022
Estimated Primary Completion Date November 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Carmen Czich, RN BSN CCRP 216-442-4204 CZICH@ccf.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04073472
Other Study ID Numbers  ICMJE IPAAF IND# IRB# are pending
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Amy Lightner, The Cleveland Clinic
Study Sponsor  ICMJE The Cleveland Clinic
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Amy Lightner, MD The Cleveland Clinic
PRS Account The Cleveland Clinic
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP