Crohn's Disease fistels
Conditions
Interventions
Study medication consists of local treatment with expanded allogeneic ASCs or
placebo. The cells will be injected in the internal opening and in up to a
maximum of three tracts per fistula.
Sponsors
Leids Universitair Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Subject must be at least 18 years of age, 2. Subjects must have had CD for at least three months from the time of initial diagnosis. The diagnosis of CD must have been confirmed endoscopically and/or radiographically, 3. Subjects must have up to a maximum of three peri-anal fistulas with per fistula up to three visible tracts assessed by MRI unresponsive to conventional treatment (antibiotics, 5ASA, SPS, corticosteroids, thiopurines, methotrexate and infliximab), 4. At some time during the course of the disease, the subject must have received both steroids, immunosuppressive agents (for example, azothioprine, 6-mercaptopurine, methotrexate) and biological therapy such as infliximab, 5. Subject is willing to participate in the study and has signed informed consent, 6. If female and of child-bearing age, subject must be non-pregnant, non-breast-feeding, and use adequate contraception. If male, subject must use adequate contraception.
Exclusion criteria
Exclusion criteria: 1. Dominant active luminal disease requiring immediate therapy, 2. Abscesses requiring surgery, 3. Pregnant or breastfeeding women, 4. Presence of significant clinical bowel obstruction, 5. Abnormal liver function, 6. Patient has severe renal insufficiency defined as patients wit a glomerular filtration rate (GFR) below 60 mL/min/1.73 m2 calculated by MDRD (Modification of Diet in Renal Disease), 7. Enteric pathogens, including C. difficile, 8. History of colonic mucosal dysplasia, 9. Subjects with a malignant tumor, except for completely resected basal or squamous cell carcinoma of skin, or patients with a prior history of malignant tumors, unless the neoplastic disease has been in remission for the previous 5 years, 10. Subjects allergic to local anesthetics or gadolinium (MRI contrast), 11. When MRI is unfeasible (e.g. due to the presence of a pacemaker or in case of claustrophobia), 12. Changes in concomitant medication: - 5-ASA and steroids (prednisone max. 15 mg/d) should be on a stable dose for at least 2 weeks, - Tacrolimus or cyclosporine should not be administered in the 4 weeks prior to study, - Immunosuppressants (e.g. azathioprine, 6MP or methotrexate) should be on a stable dose for a te least 6 weeks, - Infliximab or other anti-TNF antibody therapy should not be administered within 8 weeks prior to enrollment in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The number of adverse and serious adverse events, The reduction in the number of draining fistulas at 12 weeks. Healing being defined as absence of discharge and complete re-epithelization of the external opening of the fistula and absence of collections of >=2 cm directly related to the treated fistulas tracts as measured by MRI. | — |
Secondary
| Measure | Time frame |
|---|---|
| .1. To compare endoscopic changes before and after ASC treatment using the Crohn's disease endoscopic index of severity (CDEIS) and simplified endoscopic activity score for Crohn*s disease (SES-CD); 2. To evaluate the quality of life in patients before and after ASC treatment, using Short-Form-36 (SF-36) and Inflammatory Bowel Disease Questionnaire (IBDQ) scores; 3. To assess changes Crohn*s disease activity index (CDAI) and in the perianal disease activity index (PDAI) before and after ASC treatment; 4. To compare the incidence of peri-anal surgery between the study groups; 5. To summarize the changes from baseline in serum CRP ; 6. To evaluate different MRI classifications; 7. To asses the immunogenicity of ASCs; 8. To study the immunological effects of allogeneic ASC treatment on peripheral blood mononuclear cells in co-culture systems; 9. To asses the T cell repertoire and immunological properties before and after ASCs in patients with active luminal disease prior to treatment. | — |
Countries
Netherlands
Outcome results
None listed