Autologous Adipose Tissue in the Treatment of Systemic Sclerosis Digital Ulcers (ADUL-SSc)

ASST Gaetano Pini-CTO

Status: Unknown

Conditions: Systemic Sclerosis; Digital Ulcer

Treatments: Procedure: Sham procedure; Procedure: Autologous fat grafting

Study type: Interventional

Funder types: Other

Identifiers

NCT03406988

ID Sperimentazione 138

Details and patient eligibility

About

A randomized controlled trial will be performed to confirm preliminary uncontrolled data indicating that regional adipose tissue grafting is effective in inducing digital ulcer healing in patients with systemic sclerosis.

Systemic Sclerosis patients with digital ulcers will be randomized to be blindly treated with adipose tissue implantation or a sham procedure. Adipose tissue grafting will consist of injection at the base of the finger with digital ulcer of 0.5-1 ml of adipose tissue after centrifugation of fat aspirate. Sharm procedure will consist of false liposuction and local injection of saline solution.

The primary end-point will be to compare the cumulative prevalence of healed digital ulcers in the two groups within the following 8 weeks.

Full description

Systemic sclerosis (SSc) is an autoimmune disease characterized by a multifactorial pathological process where a central role is played by the progressive loss of the microvascular bed, with the consequent fibrotic changes in the involved organs and tissues.

The most advanced stages of capillary loss may induce the formation of digital ulcers (DUs) on the fingertips.The healing of DUs is often a lengthy process requiring accurate and intensive topical and systemic treatment. Nevertheless, in a significant number of cases this therapeutic approach is ineffective and distal necrosis with subsequent tissue loss or phalangeal amputation may eventually occur.

In a recent open pilot study performed by Del Papa et al., it has been demonstrated that autologous adipose tissue grafting (AT-G), which is known to contain both adipose-derived stem cells and a stromal/vascular fraction, was effective in inducing prompt healing of long lasting DUs localized in the fingertips of a small number of patients with SSc. The DU healing was accompanied by the rapid disappearance of local ischemic pain and evidence of a partial restoration of the capillary bed in the digits when assessed by nailfold videocapillaroscopy (NVC).

With the purpose of confirming these preliminary results, the investigators have designed a monocentric randomized controlled study. In accordance with the study protocol, patients with a typical SSc-related DU on the fingertip will be randomized to undergo a regional AT-G with autologous fat as active therapy or a 'sham' procedure (SP) - that simulates the active treatment - as placebo treatment. All of the patients with SSc enrolled in both arms will be blind regarding the treatment received. Furthermore, during the study period all of the enrolled patients will receive the same systemic vasoactive and topical therapy.

Enrollment: 46 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients candidate for enrollment in the study have to meet the 2013 classification criteria of the American College of Rheumatology/European League Against Rheumatism for SSc;
• Patients may have either the limited cutaneous or the diffuse cutaneous variants of SSc;
• All of the candidate patients must have only one active DU (cardinal ulcer), lasting for at least 6 weeks prior to enrolment time and showing no tendency to heal despite intravenous iloprost (0.5-2 ng/Kg/min), the oral administration of calcium-channel blockers (nifedipine) and local medication with surgical removal of necrotic tissue.

Exclusion criteria

• Presence of severe extra-cutaneous manifestations, such as cardiac, lung and renal involvement;
• Concomitant treatment with immune-suppressive therapies (including prednisone equivalent >10 mg);
• Current therapy with dual and selective endothelin inhibitors;
• Concomitant diabetes and/or other vascular diseases;
• Current pregnancy or breastfeeding.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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46 participants in 2 patient groups, including a placebo group

Autologous fat grafting

Experimental group

Description:

Implantation of 0.5-1 ml of autologous AT at the base of the finger with DU.

Treatment:

Procedure: Autologous fat grafting

Sham procedure

Placebo Comparator group

Description:

False liposuction followed by the injection of 0.5-1 ml of 0.9% saline solution at the base of the affected finger.

Treatment:

Procedure: Sham procedure