fistula M. Crohn
Conditions
Interventions
MSC implantation will be preceded by surgical localization, curettage of the
fistulous tract and closure of the internal opening. Three escalating doses
will be tested, in a total of three cohorts.
Sponsors
Leids Universitair Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: a) Men and women of at least 18 years of age; b) Patient must have had CD (for at least 3 months from the time of initial diagnosis). The diagnosis of CD must have been confirmed by endoscopic and histologic evidence; c) CDAI score of
Exclusion criteria
Exclusion criteria: a) Patients with evidence of acute peri-anal infection, presence of peri-anal abscesses larger than 2 cm, and anal or rectal stricture; b) Patients with evidence of any infections needing antibiotic treatment. c) Rectovaginal fistulas, or complex peri-anal fistulas with more than two internal openings; d) Patients suffering from renal- or hepatic failure. e) Use of any investigational drug within 1 month prior to screening or within 5 half-lives of the investigational agent, whichever is longer; f) Patient is allergic to gadolinium (MRI contrast agent); g) Patient with severe renal insufficiency defined as patients with a glomerular filtration rate (GFR) below 60 mL/min/1.73 m2. GFR = 186.3 x (serum creatinine)-1.154 x (age in years)-0.203 x 1.212 (if patient is black) x 0.742 (if female); h) Due to the high strength electromagnetic fields that will be used during MRI there is a risk of interference with any metallic implants in the body. The following conditions will disqualify patients from having an MRI and will be excluded from this study: * electronically, magnetically, and mechanically activated implants * ferromagnetic or electronically operated stapedial implants * cardiac pacemakers/carotid sinus pacemaker implant * hemostatic clips * metallic splinters in the orbit * insulin pumps and nerve stimulators * lead wires or similar wires * metal intrauterine device i)Change in concomitant medication: *Steroids must be stable for at least 4 weeks prior to enrolment, *5-ASA should be on a stable dose > 4 weeks prior to enrolment, *Immunosuppressants (e.g. azathioprine, 6MP or methotrexate) should be on a stable dose > 8 weeks prior to enrolment, *Infliximab or other anti-TNF antibody therapy should be on a stable dose > 8 weeks prior to enrolment. j) Clausterphobia; k) Documented HIV infection. Active hepatitis B, hepatitis C or TB; l) Patients who currently have or who have had an opportunistic infection (e.g., herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 6 months prior to screening; m) Serious infections (such as pneumonia or pyelonephritis) in the previous 3 months. Less serious infections (such as acute upper respiratory tract infection [colds] or simple urinary tract infection) need not be considered exclusions at the discretion of the investigator; n) Malignancy within the past 5 years (except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence); o) History of lymphoproliferative disease including lymphoma; p) Patient is unwilling or unable to comply with the study procedures.
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| At 12 weeks 1. To assess changes in the Crohn*s Disease Activity Index (CDAI), the Perianal Disease Activity Index (PDAI) and the adapted Vaizey fecal incontinence score before and after MSC treatment; 2. To compare endoscopic changes before and after local bmMSC treatment using the Crohn*s Disease Endoscopic Index of Severity (CDEIS) and simplified endoscopic activity score for Crohn*s disease (SES-CD); 3. To evaluate the effect of local treatment with autologous bmMSCs on the quality of life of patients with fistulizing CD using the Inflammatory Bowel Disease Questionnaire (IBDQ) and Short Form (SF)-36 score; 4. To summarize the changes from baseline compared to 12 weeks in serum CRP. At 12 and 24 weeks 5. To assess the incidence of surgical intervention and infections. | — |
Primary
| Measure | Time frame |
|---|---|
| 1. To assess the safety (incidence of intervention related [serious] adverse events) and tolerability of the surgical intervention alone or the surgical intervent with local administration of different doses of allogeneic MSCs in fistula tracts of patients with refractory CD. 2. To document the efficacy of different doses of allogeneic bmMSCs in the induction of response for active fistulizing CD. | — |
Countries
Netherlands
Outcome results
None listed