Allogeneic Bone Marrow Derived Mesenchymal Stem Cells for the Treatment of Fistulas in Patients with Refractory Perianal Crohn*s Disease

Completed

Conditions: fistula
M. Crohn
10017969

Registration Number: NL-OMON36386

Lead Sponsor: eids Universitair Medisch Centrum

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 21

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 <250 at screening and baseline;
d) Peri-anal fistulas must be refractory to conventional medical therapy. Which means that at some time during the course of the disease, patient must have received both steroids and immunosuppressive agents (for example, azathioprine, 6-mercaptopurine, methotrexate, or infliximab) which did not result in an adequate response to treatment;
e) Patients with previous surgical attempts to eradicate perianal fistulas are eligible for inclusion as are patients with setons in situ. Setons will be removed during the surgical procedure
f) Patients included in the study might be receiving 5-aminosalicylic acid (5-ASA), steroids, azathioprine, 6-mercaptopurine (6-MP), methotrexate, infliximab or any similar drug at the time of enrolment, provided the following conditions are fulfilled at screening:
The dose of 5-ASA (both oral and rectal) must have been stable for at least 4 weeks prior to enrolment.
The dose of steroids must be stable for at least 4 weeks prior to enrolment.
The dose of immunosuppressants (for example azathioprine, 6MP, or methotrexate) must have been stable for at least 8 weeks prior to enrolment and the patient on therapy for at least three months prior to enrolment.
The dose of infliximab or other anti-TNF drug must have been stable for at least 8 weeks prior to enrolment;
g) No need for immediate surgery (obstruction, strictures or abscess);
h) If female and of child-bearing age, patient must be non-pregnant, non-breastfeeding, and use adequate contraception;
i) 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 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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>1. To assess the safety (incidence of intervention related [serious] adverse<br /><br>events) and tolerability of the surgical intervention alone or the surgical<br /><br>intervent with local administration of different doses of allogeneic MSCs in<br /><br>fistula tracts of patients with refractory CD.<br /><br>2. To document the efficacy of different doses of allogeneic bmMSCs in the<br /><br>induction of response for active fistulizing CD.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>At 12 weeks<br /><br>1. To assess changes in the Crohns Disease Activity Index (CDAI), the Perianal<br /><br>Disease Activity Index (PDAI) and the adapted Vaizey fecal incontinence score<br /><br>before and after MSC treatment;<br /><br>2. To compare endoscopic changes before and after local bmMSC treatment using<br /><br>the Crohns Disease Endoscopic Index of Severity (CDEIS) and simplified<br /><br>endoscopic activity score for Crohn*s disease (SES-CD);<br /><br>3. To evaluate the effect of local treatment with autologous bmMSCs on the<br /><br>quality of life of patients with fistulizing CD using the Inflammatory Bowel<br /><br>Disease Questionnaire (IBDQ) and Short Form (SF)-36 score;<br /><br>4. To summarize the changes from baseline compared to 12 weeks in serum CRP.<br /><br><br /><br>At 12 and 24 weeks<br /><br>5. To assess the incidence of surgical intervention and infections.</p><br>

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