To assess the safety (incidence of drug-related adverse events) and efficacy of allogeneic ASCs for the treatment of complex perianal Crohn*s fistulas compared to placebo.
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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 outcome
.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.
Background summary
Crohn*s disease (CD) is a sever disorder with significant morbidity and major
impact on life. CD can affect any part of the digestive system and symptoms of
this chronic illness include abdominal pain, bloating, nausea, vomiting and
(bloody) diarrhea. CD also causes mucosal ulcerations, strictures (narrowing of
a hollow structure due to scar tissue and swelling) and fistulas (abnormal
passages from the intestines to another organ or to the skin).
There is an unmet need for effective medical therapeutics in patients with
complex perianal fistulas in CD not responding to the conventional strategies,
including biological therapies. The current study is designed to assess the
safety and efficacy of expanded allogeneic adipose tissue derived stem cells
(ASCs) for the treatment of refractory complex perianal fistulas in CD
patients.
Study objective
To assess the safety (incidence of drug-related adverse events) and efficacy of
allogeneic ASCs for the treatment of complex perianal Crohn*s fistulas compared
to placebo.
Study design
This is a randomized, double-blinded, placebo controlled, prospective, clinical
phase II study.
Intervention
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.
Study burden and risks
No side effects known in autologous setting.
Albinusdreef 2
2333 ZA Leiden
Nederland
Albinusdreef 2
2333 ZA Leiden
Nederland
Listed location countries
Age
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
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
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
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2008-000460-17-NL |
| CCMO | NL22722.000.08 |