Evaluation of Local Co-administration of Autologous ADIpose Derived Stromal Vascular Fraction With Microfat for Refractory Perianal CROHN's Fistulas.

Study Overview
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Brief Summary
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Autologous ADSVF constitutes an innovative therapeutic strategy that concentrates various types of regenerative stem cells and paracrine factors able to promote angiogenesis and tissue repair. Together with the ease of collection from a minimally manipulated lipoaspirate, the unique properties of ADSVF offer new opportunities for fistulas' healing in patients with CD. The use of ADSVF is currently developed in many clinical fields based on safety and efficacy data. Our ADICROHN pilot study evaluating safety and tolerance of local administration of autologous ADSVF with microfat in CD patients with complex perianal fistula refractory to conventional medical and surgical therapy showed that this novel therapeutic approach appears feasible and safe. However the therapeutic potential of local this combined treatment in healing refractory perianal Crohn's fistulas still remains to be demonstrated. The main objective of this study is to assess the efficacy of local injection of autologous ADSVF and microfat versus placebo for the treatment of complex refractory perianal Crohn's fistulas at week 24. The efficacy will be assessed on clinical assessment of closure of all the external openings that were drained at baseline, and MRI confirmation of absence of collections > 2 cm of the treated perianal fistulas at week 24.

Detailed Description
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Autologous ADSVF constitutes an innovative therapeutic strategy that concentrates various types of regenerative stem cells and paracrine factors able to promote angiogenesis and tissue repair. Together with the ease of collection from a minimally manipulated lipoaspirate, the unique properties of ADSVF offer new opportunities for fistulas' healing in patients with CD. The use of ADSVF is currently developed in many clinical fields based on safety and efficacy data. Our ADICROHN pilot study evaluating safety and tolerance of local administration of autologous ADSVF with microfat in CD patients with complex perianal fistula refractory to conventional medical and surgical therapy showed that this novel therapeutic approach appears feasible and safe. However the therapeutic potential of local this combined treatment in healing refractory perianal Crohn's fistulas still remains to be demonstrated. B. Primary objective/endpoint The main objective of this study is to assess the efficacy of local injection of autologous ADSVF and microfat versus placebo for the treatment of complex refractory perianal Crohn's fistulas at week 24 (W24), The efficacy will be assessed on clinical assessment of closure (despite gentle finger compression) of all the external openings that were drained at baseline, and MRI confirmation of absence of collections > 2 cm of the treated perianal fistulas at week 24.

Official Title
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Double-blind Randomised Placebo Controlled Study Evaluating Local Co-administration of Autologous ADIpose Derived Stromal Vascular Fraction With Microfat for Refractory Perianal CROHN's Fistulas.

Conditions
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Crohn Disease

Intervention / Treatment
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* Combination Product: local co-administration of autologous ADIpose
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Patients with Crohn's Disease (CD) diagnosed at least 6 months earlier in accordance with accepted clinical, endoscopic, histological and/or radiologic criteria Presence of refractory complex perianal fistulas assessed by clinical assessment during examination under anaesthesia (preparation treatment) and MRI. Non-active or mildly active luminal CD defined by a CDAI ≤ 220 Patients of either sex aged 18 years or older Good general state of health according to clinical history and a physical examination For women of a childbearing age, they must have negative serum or urine pregnancy test (sensitive to 25 IU human chorionic gonadotropin [hCG]). Both men and women should use appropriate birth control methods defined by the investigator. Exclusion Criteria: Presence of dominant luminal active Crohn's disease requiring immediate therapy CDAI > 220 Patient naïve to specific treatment for perianal fistulising Crohn's disease Presence of an abscess or collections > 2 cm, unless resolved in the preparation procedure Rectal and/or anal stenosis if this means a limitation for any surgical procedure Patient with ongoing steroid treatment or treated with steroids in the last 4 weeks Malignant tumour or patients with a prior history of any malignant tumour, including any type of fistula carcinoma Current or recent history of abnormal, severe, progressive, uncontrolled infectious, hepatic, haematological, gastrointestinal (except CD), endocrine, pulmonary, cardiac, neurological, psychiatric, or cerebral disease Congenital or acquired immunodeficiencies Contraindication to local anaesthetics or gadolinium (MRI contrast) Contraindication to MRI scan, (e.g., due to the presence of pacemakers, hip replacements or severe claustrophobia) Pregnant or breastfeeding women Contraindication to the anaesthetic or surgical procedure BMI < 18 to insure adequate abdominal or other subcutaneous adipose tissue accessible by lipoharvest Any active viral infection follows: HIV, HTLV I et II, VHB, VHC and Syphillis

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment<br>CD patients with complex refractory perianal fistula refractory to conventional medical and surgical therapy referred to the gastroenterology departments of the 3 centers in charge of treatment local co-administration of autologous ADIpose will be performed | Combination Product: local co-administration of autologous ADIpose<br>* local co-administration of autologous ADIpose derived stromal vascular fraction and microfat for refractory perianal CROHN's fistulas Each batch of the final product is composed of one 5 mL syringes containing 25,9 +/- 10,7 millions viable cells. Each syringe will be obstructed with a sterile stopper and packaged in an external packaging.<br>|
| Placebo Comparator: placebo<br>CD patients with complex refractory perianal fistula refractory to conventional medical and surgical therapy referred to the gastroenterology departments of the 3 centers in charge of treatment local co-administration of placebo will be performed | Other: placebo<br>* local co-administration of placebo The study placebo will consist of a saline solution for intralesional administration and will follow the same administration schema described for the SFV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinically evaluated | number of fistula closure | 24 weeks (w) | 
| Magnetic resonance imaging (MRI) | confirmation of absence of collections > 2 cm of the treated perianal fistulas | weeks 24 | 
| Magnetic resonance imaging (MRI) | confirmation of absence of collections > 2 cm of the treated perianal fistulas | weeks 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| a complete cessation of suppuration |  | weeks4, weeks12, weeks24, weeks52 | 
| closure of all the external openings |  | weeks4, weeks12 | 
| Index PDAI (Perianal Disease Activity ) |  | weeks4, weeks12, weeks24 and weeks52 | 
| improvement of Quality of Life Short Inflammatory Bowel Disease Questionnaire (SIBDQ) (QoL) |  | weeks4, weeks12, weeks24 and weeks52 | 
| Crohn's Disease Activity Index (CDAI) |  | weeks4, weeks12, weeks24 and weeks52 | 
| Reduction of anal incontinence severity (Wexner score) |  | weeks4, weeks12, weeks24 and weeks52 |