Subcutaneous Injection of Autologous Adipose Tissue-derived Stromal Vascular Fraction Into the Fingers of Patients With Systemic Sclerosis (scleradec2)

Subcutaneous Injection of Autologous Adipose Tissue-derived Stromal Vascular Fraction Into the Fingers of Patients With Systemic Sclerosis : Controlled Clinical Trial With Efficacy Assessment

Systemic sclerosis (SSc) is an auto-immune orphan disease mainly characterized by an alteration of the microvascular network, and by cutaneous and visceral fibrosis. Hands are frequently affected, as a consequence of ischemic phenomena and cutaneous fibrosis.

. The injection of adipose autologous tissue is a common practice in plastic surgery, and has been known for over a century. Adipose tissue, originally used to increase volume, is also characterized by trophic properties associated to stromal vascular fraction (SVF), which contain multipotent stem cells, capable of tissue repair. Interestingly, some SVF cells can be angiogenic and anti-inflammatory, which could improve damage seen with SSc.

A prior study (the SCLERADEC protocol: ClinicalTrials.gov NCT01813279) has already allowed the safety and tolerance at 6 months of the subcutaneous injection of SVF in the fingers of twelve patients to be proven.

The encouraging results have encouraged us to propose a trial which would bear on a higher number of patients and include a control group.

Study Overview

• Status: Terminated
• Conditions: Scleroderma, Systemic
• Intervention / Treatment: Drug: Ringer lactate; Drug: Stromal Vascular fraction

Detailed Description

Systemic sclerosis (SSc) is an auto-immune orphan disease mainly characterized by an alteration of the microvascular network, and by cutaneous and visceral fibrosis. Hands are frequently affected, as a consequence of ischemic phenomena and cutaneous fibrosis. As a result, patients suffer from everyday disability, with consequences on their occupational activities and social contact, sometimes severely altering their quality of life. To date, no anti-fibrosis treatment has proven effective; existing vasodilation treatments are unfortunately not very effective, and are associated with adverse effects or restrictions. It is consequently of utmost importance that an effective treatment for sclerodermic hands be developed. The injection of adipose autologous tissue is a common practice in plastic surgery, and has been known for over a century. Adipose tissue, originally used to increase volume, is also characterized by trophic properties associated to stromal vascular fraction (SVF), which contain multipotent stem cells, capable of tissue repair. Interestingly, some SVF cells can be angiogenic and anti-inflammatory, which could improve damage seen with SSc. The injection of SVF into the fingers would also make it possible to control the production of the extracellular matrix and to improve the balance between fibrosis and fibrolysis, resulting in an improvement of cutaneous sclerosis.

A prior study (the SCLERADEC protocol: ClinicalTrials.gov NCT01813279) has already allowed the safety and tolerance at 6 months of the subcutaneous injection of SVF in the fingers of twelve patients to be proven. Secondary efficacy endpoints evaluated at 2 months (M2) and 6 months (M6) showed an improvement in disability, pain, severity of Raynaud's phenomenon, trophicity, the number of digital ulcers, hand mobility and in the quality of life. These encouraging results have encouraged the investigators to propose a trial which would bear on a higher number of patients and include a control group.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Marseille, France, 13354
    • Assistance Publique Hopitaux de Marseille

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Systemic Sclerosis ( limited or diffuse cutaneous shape)
• Men and women of more than 18 years old
• Patients wishing for a therapeutic alternative
• Functional Disability of the dominant hand authenticated by a functional index of the hand of Cochin functional scale upper to 20

Exclusion Criteria:

• Body mass index (weight in kilograms divided by height in meters squared) lower than 18
• Finger infection (including infected ulcer, ulcer with signs of local inflammation and clinical suspicion of osteitis)
• Contraindication to surgery
• Prescription of a new systemic treatment for SSc in the month before the inclusion
• Subjects infected with HIV, HCV ( hepatitis C virus) , HBV (hepatitis B virus), HTLV ( human T-cell leukemia virus) and syphilis
• Pre-menopausal women of reproductive age, taking no contraceptive method
• Patients receiving immunosuppressive therapy not including corticosteroid therapy < 10 mg/D and methotrexate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Stromal Vascular Fraction; The injection is made for the patients of the both groups in the sub-dermic plan on the side faces of fingers distal and proximal or 4 times 0,25ml by finger, all in all every finger will be injected of 1ml of diluted Stromal Vascular Fraction ( experimental group) , or placebo (ringer lactate) ( placebo group)	Drug: Stromal Vascular fraction
Placebo Comparator: Placebo; The injection is made for the patients of the both groups in the sub-dermic plan on the side faces of fingers distal and proximal or 4 times 0,25ml by finger, all in all every finger will be injected of 1ml of diluted Stromal Vascular Fraction ( experimental group) , or placebo ( placebo group)	Drug: Ringer lactate; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cochin hand functional scale	effects of SVF injections in the fingers of patients suffering from SSc evaluated at 3 months, in comparison to the control group	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the pain in the hands (EVA pain scale),	effects of SVF injections in the fingers of patients suffering from SSc on evaluated at 1.3 and 6 months, in comparison to the control group	6 months
the quality of life- score adapted to scleroderma (SHAQ)	effects of SVF injections in the fingers of patients suffering from SSc , evaluated at 1.3 and 6 months, in comparison to the control group	6 months
the mobility(score de Kapandji et distance pulpe/pli palmaire distal)	effects of SVF injections in the fingers of patients suffering from SSc , evaluated at 1.3 and 6 months, in comparison to the control group	6 months
the strength(Jamar et Pinch test)	effects of SVF injections in the fingers of patients suffering from SSc , evaluated at 1.3 and 6 months, in comparison to the control group	6 months
the finger tactile sensitivity	effects of SVF injections in the fingers of patients suffering from SSc , evaluated at 1.3 and 6 months, in comparison to the control group	6 months
the trouble trophicity (health assesment questionnaire)	effects of SVF injections in the fingers of patients suffering from SSc , evaluated at 1.3 and 6 months, in comparison to the control group concerning trophicity: Rodnan score modified for the hand, finger circumference with a ring sizer, monitoring of existing ulcers and of the onset of new ulcers	6 months
the severity (frequency and intensity of crises) of Raynaud's phenomenon	effects of SVF injections in the fingers of patients suffering from SSc , evaluated at 1.3 and 6 months, in comparison to the control group concerning severity of Raynaud's phenomenon	6 months
the vascular suppression score	effects of SVF injections in the fingers of patients suffering from SSc , evaluated at 1.3 and 6 months, in comparison to the control group concerning vascular suppression score calculated using nail-fold capillaroscopy	6 months

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Investigators: Principal Investigator: Brigitte GRANEL, MD, Assistance Publique Hopitaux de Marseille

Publications and helpful links

General Publications

• Daumas A, Magalon J, Jouve E, Casanova D, Philandrianos C, Abellan Lopez M, Mallet S, Veran J, Auquit-Auckbur I, Farge D, Levesque H, Benhamou Y, Arnaud L, Giraudo L, Dumoulin C, Giverne C, Boyer O, Giuliani A, Bourgarel V, Harle JR, Schleinitz N, Brunet J, Pers YM, Ferreira R, Cras A, Boccara D, Larghero J, Chateau J, Hot A, Dignat-George F, Magalon G, Sabatier F, Granel B. Adipose tissue-derived stromal vascular fraction for treating hands of patients with systemic sclerosis: a multicentre randomized trial Autologous AD-SVF versus placebo in systemic sclerosis. Rheumatology (Oxford). 2022 May 5;61(5):1936-1947. doi: 10.1093/rheumatology/keab584.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2015
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): March 1, 2019

Study Registration Dates

• First Submitted: August 31, 2015
• First Submitted That Met QC Criteria: September 23, 2015
• First Posted (Estimate): September 24, 2015

Study Record Updates

• Last Update Posted (Actual): March 5, 2019
• Last Update Submitted That Met QC Criteria: March 4, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Connective Tissue Diseases; Scleroderma, Systemic; Scleroderma, Diffuse
• Other Study ID Numbers: 2014-003321-17