To assess the safety of endoscopic injected allogeneic bone marrow derived mesenchymal stromal cells (BMMSCs) in refractory proctitis.
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The safety, tolerability and feasibility of endoscopic injected MSCs in the
distal colon of patients with refractory proctitis after 6 weeks.
Secondary outcome
At 2, 6 and 24 weeks
1. To assess changes in the Mayo Score (appendix C) before and after BMMSC
treatment; as an indication of efficacy.
At 2, 6, 12 and 24 weeks
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.
At 6 and 24 weeks
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.
At 6, 12, 24 weeks
6. To evaluate the effect of local treatment with allogeneic BMMSCs on the
quality of life using the Short Form Health Survey (SF-36) (appendix F) and the
short Inflammatory Bowel Disease Questionnaire (sIBDQ) (appendix G).
Background summary
Patients with inflammatory bowel disease can present with proctitis,
inflammation limited to the rectum. Although most of the patients with
proctitis respond to conventional local 5-aminosalicylicacid (5-ASA) or
corticosteroid treatment, a subset does not. For this group the next treatment
option is a systemic immunosuppressive drug with considerable side-effects.
Therefore, new local therapies for proctitis are needed.
Study objective
To assess the safety of endoscopic injected allogeneic bone marrow derived
mesenchymal stromal cells (BMMSCs) in refractory proctitis.
Study design
Fourteen patients will receive allogeneic BMMSCs. BMMSCs will be injected
during endoscopy in 4 to 8 places in the inflamed rectum (number of injections
depending on the length of inflammation). Seven patients will be treated with
5x106 MSCs/ spot and seven patients with 10x106 MSCs/ spot.
Intervention
Endoscopically injected BMMSCs in the rectum.
Study burden and risks
In a recent review no side effects are associated with MSC therapy. However
based on in vitro data potential risks of this study include: i) the
suppression of immune responses resulting in an increased rate of infections.
It should be noted that the current immunosuppressive treatment strategies for
ulcerative colitis are associated with higher immune suppression risks; ii)
tumorigenicity and ectopic tissue formation. To evaluate these potential risks,
patients will be followed for 1 year following MSC treatment. For more
detailed information regarding safety refer to the enclosed IB.
Refractory UP is a clinical problem, with limited effective treatments and
severe impairment of patient*s quality of life. The potent immunomodulatory
effects and contribution to tissue repair of MSCs, together with the
preliminary results of our latest study with allogeneic BMMSC in perianal
fistulizing CD and our recent animal study, suggest that local injection of
these cells could be a promising option for treatment of refractory UP. The
local injection of allogeneic BMMSCs could avoid in these patients surgery to
create a stoma or longstanding use of systemic medication, which can both lead
to a significantly impaired quality of life. In light of the above, we believe
that the risks of the proposed procedure are minor.
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
Inclusion criteria
a) Men and women >= 18 years of age;
b) Patient must have ulcerative colitis 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
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, except for a successfully removed sporadic adenoma;
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
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-003524-75-NL |
| CCMO | NL63157.000.17 |
| OMON | NL-OMON21802 |