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

Официальное название

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.

Обзор

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.

Подробное описание

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.

Вмешательства

• Комбинированный продукт local co-administration of autologous ADIpose
  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.
• Другое placebo
  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

Первичные конечные точки

• clinically evaluated [Срок оценки: 24 weeks (w)]
• Magnetic resonance imaging (MRI) [Срок оценки: weeks 24]
• Magnetic resonance imaging (MRI) [Срок оценки: weeks 52]

Вторичные конечные точки (6)

• a complete cessation of suppuration [Срок оценки: weeks4, weeks12, weeks24, weeks52]
• closure of all the external openings [Срок оценки: weeks4, weeks12]
• Index PDAI (Perianal Disease Activity ) [Срок оценки: weeks4, weeks12, weeks24 and weeks52]
• improvement of Quality of Life Short Inflammatory Bowel Disease Questionnaire (SIBDQ) (QoL) [Срок оценки: weeks4, weeks12, weeks24 and weeks52]
• Crohn's Disease Activity Index (CDAI) [Срок оценки: weeks4, weeks12, weeks24 and weeks52]
• Reduction of anal incontinence severity (Wexner score) [Срок оценки: weeks4, weeks12, weeks24 and weeks52]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Другое

Центры проведения

Франция · 1 центр

• Assistance Publique Des Hopitaux de Marseille — Marseille

Публикации

• Guillo L, Grimaud F, Houser F, Prost C, Jouve E, Philandrianos C, Abellan M, Veran J, Visee C, Beyer-Berjot L, Desjeux A, Dignat-George F, Leone M, Grimaud JC, Sabatier F, Serrero M, Magalon J. Three-year outcome of local injection of autologous stromal vascular fraction cells and microfat in refractory perianal fistulas of Crohn's disease. Stem Cell Res Ther. 2022 Feb 9;13(1):67. doi: 10.1186/s13 PMID 35139888

Идентификаторы

NCT: NCT04010526 · RCAPHM18_0013

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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