Crohn Disease
Conditions
Keywords
Crohn's disease, perianal fistula, regenerative medicine, immunomodulation, allogeneic adipose-derived stem cell
Brief summary
Perianal fistulas are in the forefront (42 to 72, 4%) of morbid complication of Crohn's disease, affecting nearly one- third of patients and complicating abscesses in 35-48% of cases. The current treatment is based on the combination of drainage (proctologic and surgical), and biologics techniques, but the failure rate varies from 30 to 80%. Actually, innovative cell therapy procedures are validated by Cell-Easy with the use of allogenic mesenchymal stem cells for the immunomodulatory, anti-inflammatory, angiogenic and trophic properties (CellReady®) and represent a promising option in the treatment of perianal fistulas associated with Crohn's disease. This phase I/II study is designed to evaluate the treatment of complex perianal fistulas associated with Crohn's disease, after failure of conventional treatment by injection of allogeneic cultured adipose-derived stromal cell (AdMSC) into the fistula.
Detailed description
The injection of adipose stromal cells is currently evaluated in clinical studies for repair-damaged tissues in various diseases (limb ischemia, osteoarthritis, systemic slerosis...). Immunoregulatory and anti-inflammatory properties of AdMSC's are responsible for accelerating healing and represents an innovative approach to treat perianal fistulas associated with Crohn's disease. This phase I/II study is designed to evaluate the treatment of complex perianal fistulas associated with Crohn's disease, after failure of conventional treatment by injection of AdMSC (CellReady®) into the fistula. Different doses of AdMSC will be tested for a dose escalation (5.10\*7 and 10.10\*7 cells) and injected in the in the wall of the fistula.
Interventions
DRUGAdMSC (CellReady®)
At day 0, patients will have AdMSC injections. Patients will be followed-up for 6 months
Sponsors
University Hospital, Toulouse
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients over 18 years old, * Patients who signed the informed consent, * Patient affiliated to a social security system, * Controlled luminal Crohn's disease characterized by an Harvey-Bradshaw score less or equal than 8 and diagnosed on clinical, endoscopic, histological and/or radiological criteria for more than 3 months, * Colonoscopy less than a year old without ulcer in the rectum, * Presence of complex chronic perianal fistula with a maximum of two internal ports and three external ports, * Patient treated with a combined treatment (drainage on setons + anti-TNFα) and who failed conventional treatment after 6 months and whose intraluminal disease (intestinal damage) is controlled
Exclusion criteria
* Refusal of the patient to participate in the study, * Positive QuantiFERON test, * Patient with transplanted organ, * History of cancer in the last five years or lympho-proliferative disease, * Persistent bacterial or viral infection, * Patient with a contraindication to MRI, * Known allergy to Gadolinium, * Known allergy to Albumine, * End-stage organ failure, * Pregnant or breastfeeding women, * Women of childbearing age without effective contraception throughout the duration of the study, * Patient under judicial protection, under guardianship or curatorship. * Patient previously treated with ALOFISEL®
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of AdMSC by radiological evaluation at 6 months | 6 months after injection | This evaluation will be measured by disappearance of fistula tract or fistula tract present but inactive. |
| adverse events of grade ≥ 2 at 6 months | 6 months after injection | Number of adverse events of grade ≥ 2 related to the experimental treatment (CellReady®) or related to surgical/medical procedures, |
| Efficacy of AdMSC by clinical evaluation at 6 months | 6 months after injection | This evaluation will be measured by the presence or absence of flow through the internal or external orifice see in anoscopy and through the external orifice |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in quality of life | 1, 3 and 6 months after injection | Evaluation of quality of life by CAF QoL |
| Change from Baseline in disease activity | 1, 3 and 6 months after injection | Evaluation of quality of life by Harvey-Bradshaw Index |
| Change from Baseline in perianal disease activity | 1, 3 and 6 months after injection | Evaluation by perianal disease activity index (PDAI) . This index evaluate the presence of a fistula, the presence of pain and its impact on activity, the characteristics of the APL, the impact on the sexual activity |
| Change from Baseline in lesions | 1, 3 and 6 months after injection | Evaluation by Cardiff classifcation . The creation of subclasses of anoperineal lesions allowing the comparison of superimposable groups in therapeutic trials. This classification allows a standardized and precise description of lesions. |
| Safety at 1 and 3 and 6 months | 1, 3 and 6 months after injection | adverse effects will be assessed |
| Change from Baseline in patient symptoms | 1, 3 and 6 months after injection | Evaluation by Allan score: score used to assess patient symptoms and assess the impact of treatment on perineal lesions. |
| tryptophan metabolists | 3 and 6 months after injection | tryptophan metabolists are measured by high pressure liquid chromatography coupled with tandem mass spectrometry |
| faecal microbiota | 3 and 6 months after injection | faecal microbiota is analysed by Illumina Mi-Seq |
| Change from Baseline in anal incontinence | 1, 3 and 6 months after injection | Evaluation by Wexner anal incontinence score: score to quickly and simply assess the severity of anal incontinence. |
| Efficacy of AdMSC by clinical evaluation 1 and 3 months | 1 and 3 months after injection | This evaluation will be measured by the presence or absence of flow through the internal or external orifice see in anoscopy and through the external orifice |
| Efficacy of AdMSC by biological evaluation | 1, 3 and 6 months after injection | complete blood count , platelets, C-reactive protein (CRP) , liver enzyme profile, Prothrombin level (TP), activated clotting time (ACT), albumin, ferritinemia will be measured in blood samples |
Countries
France
Contacts
Primary ContactEtienne BUSCAIL, MD
Backup ContactLouis BSUCAIL, MD
Outcome results
None listed