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

Crohn Disease Clinical Trial

— ADICROHN2  

Official title:

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.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04010526
• Other study ID #: RCAPHM18_0013
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: March 2020
• Est. completion date: October 2023

Study information

• Verified date: March 2020
• Source: Assistance Publique Hopitaux De Marseille
• Contact: JEAN CHARLES GRIMAUD, MD
• Phone: +33491368739
• Email: Jean-charles.GRIMAUD[@]ap-hm.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 84
• Est. completion date: October 2023
• Est. primary completion date: July 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Crohn Disease
• Fistula

Intervention

Combination Product:
• 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.

Other:
• 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

Locations

Country	Name	City	State
France	Assistance Publique Des Hopitaux de Marseille	Marseille	Paca

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique Hopitaux De Marseille

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	clinically evaluated	number of fistula closure	24 weeks (w)
Primary	Magnetic resonance imaging (MRI)	confirmation of absence of collections > 2 cm of the treated perianal fistulas	weeks 24
Primary	Magnetic resonance imaging (MRI)	confirmation of absence of collections > 2 cm of the treated perianal fistulas	weeks 52
Secondary	a complete cessation of suppuration		weeks4, weeks12, weeks24, weeks52
Secondary	closure of all the external openings		weeks4, weeks12
Secondary	Index PDAI (Perianal Disease Activity )		weeks4, weeks12, weeks24 and weeks52
Secondary	improvement of Quality of Life Short Inflammatory Bowel Disease Questionnaire (SIBDQ) (QoL)		weeks4, weeks12, weeks24 and weeks52
Secondary	Crohn's Disease Activity Index (CDAI)		weeks4, weeks12, weeks24 and weeks52
Secondary	Reduction of anal incontinence severity (Wexner score)		weeks4, weeks12, weeks24 and weeks52