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Evaluation of Local Co-administration of Autologous ADIpose Derived Stromal Vascular Fraction With Microfat for Refractory Perianal CROHN's Fistulas. (ADICROHN2)

Primary Purpose

Crohn Disease

Status

Unknown status

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

local co-administration of autologous ADIpose

placebo

About this trial

This is an interventional other trial for Crohn Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Assistance Publique Des Hopitaux de Marseille

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

treatment

placebo

Arm Description

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

Outcomes

Primary Outcome Measures

clinically evaluated

number of fistula closure

Magnetic resonance imaging (MRI)

confirmation of absence of collections > 2 cm of the treated perianal fistulas

Magnetic resonance imaging (MRI)

confirmation of absence of collections > 2 cm of the treated perianal fistulas

Secondary Outcome Measures

a complete cessation of suppuration

closure of all the external openings

Index PDAI (Perianal Disease Activity )

improvement of Quality of Life Short Inflammatory Bowel Disease Questionnaire (SIBDQ) (QoL)

Crohn's Disease Activity Index (CDAI)

Reduction of anal incontinence severity (Wexner score)

Full Information

NCT ID

NCT04010526

First Posted

September 6, 2018

Last Updated

March 17, 2020

Sponsor

Assistance Publique Hopitaux De Marseille

1. Study Identification

Unique Protocol Identification Number

NCT04010526

Brief Title

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

Acronym

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.

Study Type

Interventional

2. Study Status

Record Verification Date

March 2020

Overall Recruitment Status

Unknown status

Study Start Date

March 2020 (Anticipated)

Primary Completion Date

July 2022 (Anticipated)

Study Completion Date

October 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique Hopitaux De Marseille

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Crohn Disease

7. Study Design

Primary Purpose

Other

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

84 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

treatment

Arm Type

Experimental

Arm Description

Arm Title

placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Combination Product

Intervention Name(s)

local co-administration of autologous ADIpose

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

clinically evaluated

Description

number of fistula closure

Time Frame

24 weeks (w)

Title

Magnetic resonance imaging (MRI)

Description

confirmation of absence of collections > 2 cm of the treated perianal fistulas

Time Frame

weeks 24

Title

Magnetic resonance imaging (MRI)

Description

confirmation of absence of collections > 2 cm of the treated perianal fistulas

Time Frame

weeks 52

Secondary Outcome Measure Information:

Title

a complete cessation of suppuration

Time Frame

weeks4, weeks12, weeks24, weeks52

Title

closure of all the external openings

Time Frame

weeks4, weeks12

Title

Index PDAI (Perianal Disease Activity )

Time Frame

weeks4, weeks12, weeks24 and weeks52

Title

improvement of Quality of Life Short Inflammatory Bowel Disease Questionnaire (SIBDQ) (QoL)

Time Frame

weeks4, weeks12, weeks24 and weeks52

Title

Crohn's Disease Activity Index (CDAI)

Time Frame

weeks4, weeks12, weeks24 and weeks52

Title

Reduction of anal incontinence severity (Wexner score)

Time Frame

weeks4, weeks12, weeks24 and weeks52

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

JEAN CHARLES GRIMAUD, MD

Phone

+33491368739

Jean-charles.GRIMAUD@ap-hm.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

EMILIE GARRIDO PRADALIE

Organizational Affiliation

APHM

Official's Role

Study Director

Facility Information:

Facility Name

Assistance Publique Des Hopitaux de Marseille

City

Marseille

State/Province

Paca

ZIP/Postal Code

13354

Country

France

Facility Contact:

First Name & Middle Initial & Last Name & Degree

JEAN CHARLES GRIMAUD, MD

Phone

+33491368739

Jean-charles.GRIMAUD@ap-hm.fr

12. IPD Sharing Statement

Citations:

PubMed Identifier

35139888

Citation

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/s13287-022-02738-x.

Results Reference

derived

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

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