Treatment of Fistulous Crohn's Disease by Implant of Autologous Mesenchymal Stem Cells Derived From Adipose Tissue

Treatment of Fistulous Crohn's Disease by Implant of Autologous Mesenchymal Stem Cells Derived From Adipose Tissue

Primary outcome measure:

Evaluation of viability, security and tolerance of the adipose-derived mesenchymal stem cells implant (ASCs) in fistulizing Crohn's disease patients, collecting the reactions and adverse events occurred during the study.

Secondary outcome measures:

1. Evaluating the Adipose-derived mesenchymal stem cells therapeutic effect, in particular:

   • Fistulas healing efficiency
   • Changes in quality of life in patients treated
   • Changes of systemic Crohn's disease after implant
   • Relapse rate monitored among patients who achieved Adipose-derived mesenchymal Stem Cells treatment success.

2. Achieving the biological characterization of the cell product used and its correlation with the therapeutic effect measured with:

   • Phenotype study
   • Suppressor capacity study.
   • Citoquines production analysis

The aim of this study is to evaluate the role of Autologous Mesechymal Stem Cells derived from adipose tissue in the treatment of fistulous Crohn disease.

15 Crohn's disease patients with one or more enterocutaneous, recto-vaginal or complex perianal fistula, will be included.

The trial is divided in three phases:

I. - Selection: Patients evaluation for study eligibility will take place within two weeks after Informed Consent signature.

Fistulous disease will be evaluated by MRI for perianal and rectovaginal fistulas, and by CT scan in the case of enterocutaneous fistula.

Previous laboratory test and radiological studies are valid for evaluation if they were obtained within two and six months, respectively, prior to this evaluation, and in the absence of clinical changes.

II.- Treatment phase includes:

1. Liposuction procedure to obtain adipose tissue.
2. Processing and production of Autologous Mesenchymal Stem Cells from adipose tissue (ASCs)
3. ASCs implant

III.- Follow up: Study visits post-implant will take place at the 1st week (+/- 3 days), 4th week (+/- 3 days), 8th week (+/- 7 days), 12nd week (+/- 7 days), 24th week (+/- 7 days), and 1 year (+/- 7 days) after implant.

Inclusion Criteria:

1. Fistulizing Crohn´s disease patients with 1 or more enterocutaneous fistulas, recto-vaginal fistula or complex perianal fistula. The complex perianal fistula is defined as a fistula presenting one of these conditions:

   • Trans-sphincteric, supra-sphincteric or extra-sphincteric tract, determined with:
   • Clinical criteria: No palpation of the tract and surgical exploration
   • Radiological criteria: Nucleal Magnetic Resonance (NMR)or Echoendoscopy
   • Multiple fistulas
   • "Horseshoe" fistula
   • Any fistula with fecal incontinence associated
   • Any fistula with a risk of fecal incontinence as a result of:
   • previous anal fistula surgery or other perianal pathology (hemorrhoids, fissures), that involves lesions or muscular complications.
   • Obstetric or iatrogenic sphincter lesions

2. Patients with Crohn Disease (CD) at screening and been diagnosed within 12 months before acceptance of clinical, endoscopical, anatomopathological and/or radiological criteria and have a non-active CD.(Crohn´s Disease Activity Index (CDAI)≤ 200)

3. > 18 Years and both genders eligible.

4. Negative pregnancy test In female fertile subjects

5. Patient must voluntary sign the informed consent before performance of any study-related procedure not part of normal medical care.

6. Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements

Exclusion Criteria:

1. Patients with a highly active CD, i.e., if they meet any of the following criteria:

   • Presence of severe proctitis (prominent friability, spontaneous bleeding, multiple erosions, deep ulcers) or dominant active luminal disease that requires immediate treatment, revealed by rectosigmoidoscopy
   • CDAI ≥201

2. Presence of abscess or other collections not drained (revealed by basal radiologic study).

3. Presence of setons drainage, unless they are removed before treatment beginning.

4. Rectal and/ or anal stenosis revealed with rectoscopy or EBA.

5. Patients needs surgery in the perianal region for other reasons than fistulas at inclusion or within 26 weeks after treatment administration.

6. Patients who have received infliximab or any other anti-TNF agent within 8 weeks before the cell treatment administration.

7. Patients who have received tacrolimus or cyclosporine within 4 weeks before cell treatment.

8. Patients with a history of alcohol or other addictive substances abuse within 6 months before inclusion.

9. Severe uncontrolled diseases (chronic renal failure, cardio, pulmonary,…).

10. Any type of medical or psychiatric disease which are considered as exclusion criteria, in the investigator's opinion.

11. Patients with diagnosis of malignant neoplasia, except basal cell or epidermoid carcinoma of the skin or previous history of malignant tumours, except those that have no evidence of relapse for at least 5 years.

12. Subjects with congenital or acquired immunodeficiency.

13. Positive serology for Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV).

14. Patient had major surgery or serious traumatism within 6 weeks before enrolment.

15. Pregnant or breast-feeding women.

16. Physical or psychical impossibility of following the protocol requirements

17. Patients who are receiving or received other investigational drugs within 30 days prior to basal visit.

18. Impossibility of doing an radiological exploration (reaction to contrast material, pacemakers, claustrophobia,…)