BIOLOGICAL EXPLORATION OF THE VASCULAR FRACTION FROM THE ADIPOSE TISSUE OF PATIENTS WITH SCLERODERMIA (sclerabio)

BIOLOGICAL EXPLORATION OF THE VASCULAR FRACTION FROM THE ADIPOSE TISSUE OF PATIENTS WITH SCLERODERMIA IN THE CONTEXT OF THE DEVELOPMENT OF AN INNOVATIVE CELLULAR THERAPY FOR THE TREATMENT OF FUNCTIONAL HANDICAP OF THE HAND

The overall objective is to propose a comprehensive analysis of the biological properties of the stromal vascular fraction evaluated in the SCLERADEC 2 clinical trial (n = 15 available) and preserved in the biological collection, compared to healthy donors (n = 10). This characterization will focus on the exploration of the phenotypic and functional characteristics of the main cellular subpopulations present in the stromal vascular fraction of scleroderma patients likely to be associated with a better regenerative vascular or anti-fibrotic activity of the cell therapy product.

The main objective will be to validate whether the supposed mechanism of action of this innovative therapy, in relation to the representativity of the endothelial progenitors, carrying the vascular regeneration activity, is preserved in the sclerodermic context.

A total of 30 subjects (20 systemic Scleroderma patients and 10 healthy donors) will be included.

Study Overview

• Status: Unknown
• Conditions: Systemic Scleroderma
• Intervention / Treatment: Biological: Study of the gene expression profile

• Study Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

Study Locations

• France
  • Marseille, France, 13005
    • Direction de la Recherche Clinique et Innovation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with systemic scleroderma included in the SCLERADEC 2 trial and healthy volunteers who use a liposuction operation for aesthetic reasons.

Description

Inclusion Criteria:

Patients with systemic scleroderma:

• fulfilling the inclusion criteria for the SCLERADEC 2 trial: patients with systemic Scleroderma older than 18, desiring a therapeutic alternative and having a functional impotence authenticated by a functional index of Cochin's hand greater than 20.
• having given their consent for the constitution of a sample in the biological collection
• having completed the follow-up visit to M3 of the SCLERADEC 2 study to have responder / non-responder status.

Healthy volunteers:

• having recourse to a liposuction operation for aesthetic reasons,
• with a BMI between 18 and 27,
• not declaring chronic diseases,
• having signed the non-opposition

Exclusion Criteria:

Patients with systemic scleroderma:

• Body mass index (weight-to-height ratio squared) less than 18
• Major Sclerodactyly objectified by Rodnan score applied by hand> 16 (out of a total of 18 points)
• Severe tendon retraction of the fingers objectified by a defect extension in passive measure in goniometry> 90 ° C for at least 2 proximal interphalangeal joints
• Digital infection (including infected ulcer, ulcer with local inflammatory signs and clinical suspicion of osteitis)
• Pulmonary arterial hypertension and / or progressive and / or oxygen-dependent pulmonary fibrosis
• Prescription of a new systemic treatment for Systemic Scleroderma in the month prior to inclusion
• Persons infected with HIV, HCV, HBV, HTLV and syphilis
• Patients on immunosuppressants outside corticosteroid therapy <10 mg / day and methotrexate
• Known hypersensitivity to human albumin

For healthy patients and volunteers:

• Contraindication to surgery (patients on anticoagulant or antiaggregant, disorders of haemostasis, contraindication to the analgesic protocol used)
• Premenopausal women of childbearing age without contraception
• Minors
• Pregnant or lactating women
• Majors protected by law (under tutorship or curatorship)
• Persons staying in a health or social facility
• People in emergency
• Persons deprived of their liberty
• Inmates
• Non-beneficiaries of a social security scheme
• Absence or refusal of non-opposition

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
patients with systemic scleroderma; Use of the biological collection of the vascualire stromal fraction of the SCLERADEC 2 clinical trial.	Biological: Study of the gene expression profile; qPCR analysis
healthy volunteers; Recovery of a sample of adipose tissue during a liposuction operation in a context of routine cosmetic surgery.	Biological: Study of the gene expression profile; qPCR analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study of the gene expression profile	Study of the gene expression profile by qPCR	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phenotypic analysis of the cells composing the stromal vascular fraction	Phenotypic analysis performed by flow cytometry after multiple immunolabelings (CD90, CD14, CD146, CD34, CD45, DRAQ5, NucBlue Fixed Cell Stain (DAPI)) performed in accordance with the recommendations of the International Society for Cellular Therapy (ISCT) and IFATS.	18 months
Cell culture of the stromal vascular fraction to isolate and expand two populations of interest	Mesenchymal stem cells (MSCs) obtained by culturing the total stromal vascular fraction without an immunomagnetic selection step.	18 months
Cell culture of the stromal vascular fraction to isolate and expand two populations of interest	Endothelial progenitors by a magnetic immuno-separation method (CD144 microbeads kit, Mylteni biotec) for specifically isolating and expanding endothelial progenitor cells.	18 months

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2018
• Primary Completion (Anticipated): March 1, 2020
• Study Completion (Anticipated): September 1, 2020

Study Registration Dates

• First Submitted: August 7, 2018
• First Submitted That Met QC Criteria: August 10, 2018
• First Posted (Actual): August 14, 2018

Study Record Updates

• Last Update Posted (Actual): August 14, 2018
• Last Update Submitted That Met QC Criteria: August 10, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Connective Tissue Diseases; Scleroderma, Systemic; Scleroderma, Diffuse
• Other Study ID Numbers: 2018-06; IDRCB (Other Identifier: 2025-A01568-41)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No