Ulcerative Colitis Colitis Ulcerosa Inflammatory Bowel Diseases
Conditions
Interventions
Fourteen patients will receive allogeneic BMMSCs. BMMSCs will be injected during endoscopy in the inflamed rectum. Seven patients will be treated with 5x106 MSCs/ spot and seven patients with 10x106 M
Sponsors
Leiden University Medical Center
Eligibility
Inclusion criteria
Inclusion criteria: a) Men and women ≥ 18 years of age; b) Patient must have UC confirmed by endoscopic and histologic evidence; c) Inflammation must be limited to the rectum (up to 15 cm beyond the anal verge), confirmed by endoscopy maximum 3 months before baseline (slight inflammation in other parts of the colon is accepted with a maximum Mayo Score of 1); d) Moderate to severe proctitis indicated by a Mayo Score of 2 or 3; e) Proctitis must be refractory to conventional medical therapy. Which means that at some time during the course of the disease, patient must have received rectal 5-ASA therapy and rectal corticosteroid therapy for at least 4 weeks which did not result in an adequate response to treatment; f) If treated with rectal therapy, therapy must be stopped two weeks before endoscopic implantation of MSCs and only restarted after 6 weeks; g) If treated with oral 5-ASA therapy, dose must be stable for 4 weeks prior to study entry and remain on same dose during the first 6 weeks after MSC treatment; h) If treated with oral corticosteroids, dose must be stable for 2 weeks prior to study entry and remain on same dose during the first 6 weeks after MSC treatment; i) If treated with 6-mercaptopurine, methotrexate, azathioprine, vedolizumab or anti-TNF therapy patients must have been on medication for 3 months and a stable dose for 2 months prior to study entry and remain on same dose during the first 6 weeks after MSC treatment; j) If female and of child-bearing age, patient must be non-pregnant, non-breastfeeding, and use adequate contraception; k) Patient is willing to participate in the study and has signed the informed consent. Consent must be obtained prior to any study procedure.
Exclusion criteria
Exclusion criteria: a) Patients suffering from renal- or hepatic failure; b) Use of any investigational drug within 1 month prior to screening or within 5 half-lives of the investigational agent, whichever is longer; c) Positive stool culture for enteric pathogens (salmonella, shigella, and campylobacter), positive C. difficile toxin, or positive stool ova and parasite exam; d) All active infections requiring treatment; e) Patients who had tuberculosis or an opportunistic infection (e.g., herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis) within 6 months prior to screening; f) 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); g) Any dysplasia in the colon in the past 5 years; h) Very severe proctitis; expected to result in hospitalization/ surgery within 3 months; i) Previous treatment with allogeneic MSCs; j) Any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in and completing the study; k) Patient is unwilling or unable to comply with the study procedures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The safety and tolerability of endoscopic injected MSCs in the distal colon of patients with refractory proctitis after 6 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To assess changes in the Mayo Score (appendix C) before and after BMMSC treatment; as an indication of efficacy. 2. To assess changes in patient-reported outcome measures (PROMs) using the mHealth index (appendix D) [71]. 3. To summarize the changes in serum c-reactive protein (CRP) and fecal calprotectin. 4. To compare histologic disease activity before and after local BMMSC treatment using the Geboes score (appendix E). 5. To evaluate the effects of this intervention on immunological parameters and local MSC persistence. 6. To evaluate the effect of local treatment with allogeneic BMMSCs on the quality of life using the 12-item Short Form Health Survey (SF-36) (appendix F) and the short Inflammatory Bowel Disease Questionnaire (sIBDQ) (appendix G). | — |
Contacts
Public ContactAndrea van der Meulen-de Jong
Outcome results
None listed