An Innovative Treatment for Fistula-in-ano in Crohn Disease : Local Micro Reinjection of Autologous Fat and SVF

Study Overview
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Brief Summary
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Crohn's disease is a chronic inflammation of all or part of the digestive tract,  from the mouth to the anus . . Cell therapy is a new and promising approach for the treatment of inflammatory disease including Crohn's disease and fistulas. Adipose tissue seems to be an ideal source for cell therapy. This is a prospective, open, non-comparative, single center, phase I-II clinical trial. It will involve 10 patients and will be conducted over a period of 28 month. This protocol is designed to evaluate, in patients with Crohn's disease and fistula-in-ano refractory to conventional medical and surgical treatment, the safety and efficacy of local microinjection of autologous adipose tissue and SVF from microaspirate . The main objective is to assess tolerance and security. The secondary objective is to evaluate the effectiveness of this technique

Detailed Description
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Crohn's disease is a chronic inflammation of all or part of the digestive tract,  from the mouth to the anus . Anoperineal lesions are a very frequent entity in this disease (20 to 80%) and a real therapeutic challenge. Among these lesions, we were interested in fistula-in-ano that are currently difficult to treat despite a large therapeutic arsenal. Cell therapy is a new and promising approach for the treatment of inflammatory disease including Crohn's disease and fistulas. Indeed, stem cells have shown some efficacy in several indications through their differentiation potential, including fistula-in-ano in Crohn's disease. Adipose tissue seems to be an ideal source for cell therapy This is a prospective, open, non-comparative, single center, phase I-II clinical trial. It will involve 10 patients and will be conducted over a period of 28 month. This protocol is designed to evaluate, in patients with Crohn's disease and fistula-in-ano refractory to conventional medical and surgical treatment, the safety and efficacy of local microinjection of autologous adipose tissue and SVF from microaspirate. The main objective is to assess tolerance and security. The secondary objective is to evaluate the effectiveness of this technique Microaspiration is performed by a plastic surgeon under general anesthesia. He performs two types of fat removal : a sample of 120 cc wich is sent to the laboratory of cell therapy to obtain the SVF (5 cc) and a sample of 30 cc. Once treatment obtained (SVF + adipose tissue) it is administered to the patient by local mico reinjection into (SVF) and around (adipose tissue) of the fistula. This administration is made by the surgeon under a second general anesthesia after viewing the fistula and removal of setons. Then the patient is monitored with regular consultations at weeks 1, 2, 8, 16 et 48 and paraclinical (blood sample and magnetic resonance imaging of the perineum) at weeks 8 and 48 to evaluate tolerance and effectiveness of treatment. At the end of the study, results that are expected are effectiveness of local micro reinjection of autologous adipose tissue and SVF for the treatment of refractory fistula-in-ano in Crohn's disease.

Official Title
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An Innovative Treatment for Fistula-in-ano in Crohn Disease : Local Micro Reinjection of Autologous Fat and Stromal Vascular Fraction

Conditions
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Crohn Disease

Intervention / Treatment
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* Drug: stromal vascular fraction (SVF)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Disease of Crohn diagnosed for at least 6 months according to the recognized clinical, endoscopic and histological criteria Presence of fistulas died anal complex estimated by clinical examination and MRI. A fistula died anal complex is, by definition, a fistula which answers at least one of the following criteria during its evolution: (1) high, trans-sphincter, extra-sphincter or above sphincter Inter-sphincter. (2) Presence of = 2 external openings. (3) Purulent Collections associated Active or slightly active Crohn luminal, defined by a CDAI (Crohn's Disease Activity Index) = 220 Exclusion Criteria: - Disease of Crohn activates mainly luminal with a CDAI = 220 requiring an immediate treatment Patients having never received specific treatments of the anal died disease of Crohn with fistula, including by antibiotics Presence of an abscess or collections of more than 2 cms unless this problem is solved during the period of preparation Rectal and/or anal Stenosis and/or active proctitis, if it means a limitation of the surgical procedure Patient having undergone an operation of the fistula other than the drainage Patients under corticoids or by having receiving in the previous four weeks Active Malignant Tumors or history of Malignant tumors

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Crohn's disease treated by SVF<br>Patients with Crohn's disease and fistula-in-ano refractory to conventional medical and surgical treatment, treated by Stromal Vascular Fraction ( SVF) reinjection | Drug: stromal vascular fraction (SVF)<br>* stromal vascular fraction (SVF) is administered to the patient suffering of Refractory Crohn's disease around of the fistula by local mico injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| efficacy (measured as an absence of purulent collections superior to 2 cms concerning the fistula measured clinically and by MRI) | the patient is monitored with regular consultations at weeks 1, 2, 8, 16 et 48 and paraclinical (blood sample (hemogram , coagulation factors) and magnetic resonance imaging of the perineum) at weeks 8 and 48 to evaluate effectiveness of treatment. The efficacy of treatment is measured as an absence of purulent collections superior to 2 cms concerning the fistula treated at 12 and 48 weeks measured clinically and by MRI | 48 weeks | 
| safety (measured by an absence of fever and local inflammatories symptoms) | the patient is monitored with regular consultations at weeks 1, 2, 8, 16 et 48 and paraclinical (blood sample (hemogram and coagulation factors) and magnetic resonance imaging of the perineum) at weeks 8 and 48 to evaluate tolerance of treatment. The safety is measured by an absence of fever and local inflammatories symptoms measured at week 1, 2,8, 16 and 48 | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| improvement of quality of life (assessed by questionnaire) | Quality of life is assessed by questionnaire concerning (Inflammatory Bowel Disease) (SIBDQ: Short Inflammatory Bowel Disease Questionnaire) at week 2, 12, 16 et 48 | 48 weeks |