Autologous Adipose Tissue in the Treatment of Systemic Sclerosis Digital Ulcers

NCT03406988 | Unknown DMC

• 1 other identifier: ID Sperimentazione 138
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Systemic Sclerosis; Digital Ulcer

Keywords

Systemic Sclerosis; Digital Ulcer; Autologous fat grafting; Adipose tissue stem cells

Outcome Measures

Primary Outcomes (1)

• Digital Ulcer healing

  Prevalence of DU healing in the arm treated with autologous fat grafting in comparison with the prevalence of healing in the placebo group.

  8 weeks after either autologus fat grafting or sham procedure.

Secondary Outcomes (2)

• Pain evaluation by Visual Analogue Scale (VAS)

  This evaluation will be done at baseline and at the 2nd, 4th, 6th, 8th week after interventions (either autologus fat grafting or sham procedure).

• Neovascularization evaluation

  Baseline and 8 weeks after either autologus fat grafting or sham procedure.

Study Arms (2)

Autologous fat grafting

EXPERIMENTAL

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

Procedure: Autologous fat grafting

Sham procedure

PLACEBO COMPARATOR

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

Procedure: Sham procedure

Interventions

Autologous fat grafting PROCEDURE

Implantation of small amount of autologous adipose tissue at the base of the finger to induce a rapid healing of the distally located DU

Also known as: Iloprost infusion, oral nifedipine

Autologous fat grafting

Sham procedure PROCEDURE

Local injection of 0.5ml saline solution after a simulated liposuction procedure.

Also known as: Iloprost infusion, oral nifedipine

Sham procedure

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ASST Gaetano Pini-CTO: lead
• Società Italiana di Reumatologia: collaborator

Study Sites (1)

UOC Day Hospital Reumatologia, ASST G. Pini-CTO

Milan, 20122, Italy

RECRUITING

Related Publications (4)

• Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. N Engl J Med. 2009 May 7;360(19):1989-2003. doi: 10.1056/NEJMra0806188. No abstract available.

  PMID: 19420368 BACKGROUND

• Steen V, Denton CP, Pope JE, Matucci-Cerinic M. Digital ulcers: overt vascular disease in systemic sclerosis. Rheumatology (Oxford). 2009 Jun;48 Suppl 3:iii19-24. doi: 10.1093/rheumatology/kep105.

  PMID: 19487218 BACKGROUND

• Del Papa N, Di Luca G, Sambataro D, Zaccara E, Maglione W, Gabrielli A, Fraticelli P, Moroncini G, Beretta L, Santaniello A, Sambataro G, Ferraresi R, Vitali C. Regional implantation of autologous adipose tissue-derived cells induces a prompt healing of long-lasting indolent digital ulcers in patients with systemic sclerosis. Cell Transplant. 2015;24(11):2297-305. doi: 10.3727/096368914X685636. Epub 2014 Dec 12.

  PMID: 25506730 BACKGROUND

• Del Papa N, Di Luca G, Andracco R, Zaccara E, Maglione W, Pignataro F, Minniti A, Vitali C. Regional grafting of autologous adipose tissue is effective in inducing prompt healing of indolent digital ulcers in patients with systemic sclerosis: results of a monocentric randomized controlled study. Arthritis Res Ther. 2019 Jan 7;21(1):7. doi: 10.1186/s13075-018-1792-8.

  PMID: 30616671 DERIVED

MeSH Terms

Conditions

Scleroderma, Systemic; digital ulcers

Interventions

Nifedipine

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Nicoletta Del Papa, MD

  ASST Gaetano Pini-CTO

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicoletta Del Papa, MD

CONTACT

+39-0258296415; nicoletta.delpapa@asst-pini-cto.it

Claudio Vitali, MD

CONTACT

+39-0258296415; c.vitali@yahoo.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Each enrolled patient will be blind regarding the administered therapy (active and sham procedure). Evaluation of primary and secondary outcomes will be performed by assessors blind regarding the administered therapy.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Head of the Scleroderma Clinics, Rheumatology Department

Model Details: Candidate SSc patients will have only one active DU of at least 6 mm in diameter, lasting for at least 6 weeks, despite conventional vascular therapy. Patients with severe visceral manifestations, diabetes and treated with immune-suppressors and endothelin inhibitors will be excluded. Active therapy: implantation of 0.5-1 ml of autologous AT at the base of the finger with DU. Autologous AT will be obtained by liposuction from abdominal fat. SP will be blindly performed in the control group to simulate the AT-G. A false liposuction will be performed followed by the injection of 0.5-1 ml of 0.9% saline solution at the base of the affected finger. Basal therapy: weekly iloprost infusion (0.5-2 ng/Kg/min), and calcium-channel blockers (oral nifedipine 20 mg daily) will be continued during the entire observation time in all of the patients recruited in both arms of the study. The administration of analgesics to alleviate the DU-related pain will be also allowed for each patient.

Study Record Dates

• First Submitted: January 8, 2018
• First Posted: January 23, 2018
• Study Start: July 18, 2017
• Primary Completion: March 31, 2018
• Study Completion: March 31, 2018
• Last Updated: January 25, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)