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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05075811
Other study ID # 21-860
Secondary ID
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date February 1, 2022
Est. completion date November 15, 2024

Study information

Verified date April 2022
Source The Cleveland Clinic
Contact Allison Bayles, AA
Phone 216-444=0887
Email ibdstemcelltherapy@ccf.org
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this study is to determine the safety and feasibility of using Ossium vertebral Bone Marrow Derived Mesenchymal Stem Cells (vBM-MSC) to treat people with an ileal pouch anal anastomosis (IPAA) who develop a fistula in the setting of Crohn's disease of the pouch.


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.1 2 While less than 30% of patients experience short-term postoperative morbidity following IPAA,3-5 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.1,2,6-8 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.1 Given the high safety profile, and relative success in treating perianal disease, we sought to use a GMP grade allogeneic bone marrow derived MSCs to establish safety and secondarily monitor for healing in patients with ileal anal anastomosis and ileal pouch fistulas. This trial will use allogeneic bone marrow derived mesenchymal stem cells (MSCs) to produce regenerative signals. 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. Subjects who are refractory to conventional medical therapy will be considered. Subjects enrolled will be those that meet current indications.


Recruitment information / eligibility

Status Recruiting
Enrollment 20
Est. completion date November 15, 2024
Est. primary completion date November 15, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility 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. Subjects with fistulas that arise from the pouch, anastomosis, or anal canal distal to the anastomosis will both be included in enrollment. a. 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. b. 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. Failed oral antibiotic therapy -any oral antibiotic that has been attempted and has not been effective for fistula closure. 5. 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 6. Competent and able to provide written informed consent 7. Ability to comply with protocol. Exclusion Criteria 1. Change in medical management for CD in the previous 2 months or changes anticipated in the next 2 months 2. Daily use of prednisone of greater than 20 mg per day 3. Clinically significant medical conditions within the six months before administration of vBM-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. 4. Specific exclusions; - HIV - Hepatitis B or C 5. History of cancer including melanoma (with the exception of localized skin cancers) within 1 year prior to treatment 6. Investigational drug within thirty (30) days of baseline 7. Pregnant or breast feeding or trying to become pregnant 8. Contraindications to MR evaluations: e.g. pacemaker or magnetically active metal fragments, claustrophobia 9. Unwilling to agree to use acceptable contraception methods during participation in study

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Ossium vBM-MSC
Vertebral bone marrow derived mesenchymal stem cells
Other:
Placebo
Normal Saline

Locations

Country Name City State
United States Cleveland Clinic Cleveland Ohio

Sponsors (2)

Lead Sponsor Collaborator
Amy Lightner Ossium Health, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (6)

Farouk R, Pemberton JH, Wolff BG, Dozois RR, Browning S, Larson D. Functional outcomes after ileal pouch-anal anastomosis for chronic ulcerative colitis. Ann Surg. 2000 Jun;231(6):919-26. — View Citation

Fazio VW, Kiran RP, Remzi FH, Coffey JC, Heneghan HM, Kirat HT, Manilich E, Shen B, Martin ST. Ileal pouch anal anastomosis: analysis of outcome and quality of life in 3707 patients. Ann Surg. 2013 Apr;257(4):679-85. doi: 10.1097/SLA.0b013e31827d99a2. — View Citation

Foley EF, Schoetz DJ Jr, Roberts PL, Marcello PW, Murray JJ, Coller JA, Veidenheimer MC. Rediversion after ileal pouch-anal anastomosis. Causes of failures and predictors of subsequent pouch salvage. Dis Colon Rectum. 1995 Aug;38(8):793-8. — View Citation

Meagher AP, Farouk R, Dozois RR, Kelly KA, Pemberton JH. J ileal pouch-anal anastomosis for chronic ulcerative colitis: complications and long-term outcome in 1310 patients. Br J Surg. 1998 Jun;85(6):800-3. — View Citation

Ozdemir Y, Kiran RP, Erem HH, Aytac E, Gorgun E, Magnuson D, Remzi FH. Functional outcomes and complications after restorative proctocolectomy and ileal pouch anal anastomosis in the pediatric population. J Am Coll Surg. 2014 Mar;218(3):328-35. doi: 10.1016/j.jamcollsurg.2013.11.019. Epub 2013 Nov 26. — View Citation

Remzi FH, Fazio VW, Kirat HT, Wu JS, Lavery IC, Kiran RP. Repeat pouch surgery by the abdominal approach safely salvages failed ileal pelvic pouch. Dis Colon Rectum. 2009 Feb;52(2):198-204. doi: 10.1007/DCR.0b013e31819ad4b6. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Treatment related adverse events Number of participants with treatment related adverse events post-injection of 100 million vertebral bone marrow derived MSC's for the treatment of medically refractory pouch fistulizing disease as assessed by protocol Month 6
Primary Complete clinical healing Number of participants with complete clinical healing post-injection of 100 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
Primary Complete clinical healing Number of participants with complete clinical healing post-injection of 100 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 12
Primary Partial healing Number of participants with partial clinical healing,post-injection of 100 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
Primary Partial healing Number of participants with partial clinical healing,post-injection of 100 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 12
Primary Lack of response Number of participants with lack of response post-injection of 100 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
Primary Lack of response Number of participants with lack of response post-injection of 100 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 12
Primary Worsening disease Number of participants with worsening disease-injection of 100 million vertebral 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
Primary Worsening disease Number of participants with worsening disease-injection of 100 million vertebral 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 12
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