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

• ClinicalTrials.gov Identifier: NCT02558543
• Recruitment Status: Terminated
• First Posted: September 24, 2015
• Last Update Posted: March 5, 2019
• Sponsor: Assistance Publique Hopitaux De Marseille
• Information provided by (Responsible Party): Assistance Publique Hopitaux De Marseille

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Scleroderma, Systemic	Drug: Stromal Vascular fraction; Drug: Ringer lactate	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 2015
• Actual Primary Completion Date: December 2018
• Actual Study Completion Date: March 2019

Arms and Interventions

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 Name: Placebo

Outcome Measures

Primary Outcome Measures :

1. Cochin hand functional scale [ Time Frame: 3 months ]
   effects of SVF injections in the fingers of patients suffering from SSc evaluated at 3 months, in comparison to the control group

Secondary Outcome Measures :

1. the pain in the hands (EVA pain scale), [ Time Frame: 6 months ]
   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
2. the quality of life- score adapted to scleroderma (SHAQ) [ Time Frame: 6 months ]
   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
3. the mobility(score de Kapandji et distance pulpe/pli palmaire distal) [ Time Frame: 6 months ]
   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
4. the strength(Jamar et Pinch test) [ Time Frame: 6 months ]
   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
5. the finger tactile sensitivity [ Time Frame: 6 months ]
   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. the trouble trophicity (health assesment questionnaire) [ Time Frame: 6 months ]
   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
7. the severity (frequency and intensity of crises) of Raynaud's phenomenon [ Time Frame: 6 months ]
   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
8. the vascular suppression score [ Time Frame: 6 months ]
   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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

France

Assistance Publique Hopitaux de Marseille

Marseille, France, 13354

Sponsors and Collaborators

Assistance Publique Hopitaux De Marseille

Investigators

• Principal Investigator: Brigitte GRANEL, MD; Assistance Publique Hopitaux De Marseille

More Information

• Responsible Party: Assistance Publique Hopitaux De Marseille
• ClinicalTrials.gov Identifier: NCT02558543 History of Changes
• Other Study ID Numbers: 2014-003321-17
• First Posted: September 24, 2015
• Last Update Posted: March 5, 2019
• Last Verified: March 2019

Additional relevant MeSH terms:

Scleroderma, Systemic; Scleroderma, Diffuse; Connective Tissue Diseases; Skin Diseases