Clinical trial NCT02558543: Subcutaneous Injection of Autologous Adipose Tissue-derived Stromal Vascular Fraction Into the Fingers of Patients With Systemic Sclerosis
Official title: Subcutaneous Injection of Autologous Adipose Tissue-derived Stromal Vascular Fraction Into the Fingers of Patients With Systemic Sclerosis : Controlled Clinical Trial With Efficacy Assessment
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Scleroderma, Systemic
Lead sponsor: Assistance Publique Hopitaux De Marseille
Sponsor class: OTHER
First posted: 2015-09-24
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Cochin hand functional scale
timeFrame: 3 months
Secondary outcomes:
measure: the pain in the hands (EVA pain scale),
timeFrame: 6 months
measure: the quality of life- score adapted to scleroderma (SHAQ)
timeFrame: 6 months
measure: the mobility(score de Kapandji et distance pulpe/pli palmaire distal)
timeFrame: 6 months
measure: the strength(Jamar et Pinch test)
timeFrame: 6 months
measure: the finger tactile sensitivity
timeFrame: 6 months
measure: the trouble trophicity (health assesment questionnaire)
timeFrame: 6 months
measure: the severity (frequency and intensity of crises) of Raynaud's phenomenon
timeFrame: 6 months
measure: the vascular suppression score
timeFrame: 6 months
Other outcomes:
Locations:
city: Marseille
country: France
facility: Assistance Publique Hopitaux de Marseille
Study officials:
affiliation: Assistance Publique Hopitaux De Marseille
name: Brigitte GRANEL, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.