Systemic SclerosisADUL-SScNCT03406988
Autologous Adipose Tissue in the Treatment of Systemic Sclerosis Digital Ulcers
A study testing Autologous fat grafting in people with Systemic Sclerosis and Digital Ulcer, run by ASST Gaetano Pini-CTO at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Systemic Sclerosis, Digital Ulcer
- What is being tested?
- Autologous fat grafting
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 46 participants
- Where
- 1 siteItaly
- Study dates
- 18 Jul 2017to 31 Mar 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
UOC Day Hospital Reumatologia, ASST G. Pini-CTO
Milan, 20122
Nicoletta Del Papa, MD, +39-0258296415, nicoletta.delpapa@asst-pini-cto.it
About this study
Official title: Regional Grafting of Autologous Adipose Tissue in the Treatment of Systemic Sclerosis Digital Ulcers: a Prospective Randomized Controlled Study
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.
Read the detailed 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.
- Conditions
- Systemic Sclerosis, Digital Ulcer
- Being tested
- Autologous fat grafting, Sham procedure
- Keywords
- Systemic Sclerosis, Digital Ulcer, Autologous fat grafting, Adipose tissue stem cells
- Medical subject headings
- Scleroderma, Systemic, digital ulcers
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous fat graftingProcedure or surgery
Also called Iloprost infusion, oral nifedipine
Implantation of small amount of autologous adipose tissue at the base of the finger to induce a rapid healing of the distally located DU
Sham procedureProcedure or surgery
Also called Iloprost infusion, oral nifedipine
Local injection of 0.5ml saline solution after a simulated liposuction procedure.
| Study group | Role | What they receive |
|---|---|---|
| Autologous fat grafting | Experimental | Implantation of 0.5-1 ml of autologous AT at the base of the finger with DU. Receives: 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. Receives: Procedure: Sham procedure |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 8 weeks after either autologus fat grafting or sham procedure.
Secondary outcomes (2)
Pain evaluation by Visual Analogue Scale (VAS)
The pain VAS is a continuous scale comprised of a horizontal line of 10 centimeters (100 mm) in length, ranging from 0 (minimum= no pain) to 100 (worst imaginable pain). The respondents will be asked to place a line perpendicular to the VAS line at the point that represents their pain intensity. Using a ruler, the score is determined by measuring the distance (mm) on the 10-cm line between the "no pain" anchor and the patient's mark, providing a range of scores from 0-100.
In this study VAS score will be used to measure the decrease (or resolution) of pain with respect to baseline value in patients who will undergo treatment with autologous fat grafting (active arm) in comparison with patients of the placebo group.
Measured: 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
Increase of the number of capillaries assessed by NVC in the affected digit of patients treated with autologous fat grafting in comparison with patients of the placebo group.
Measured: Baseline and 8 weeks after either autologus fat grafting or sham procedure.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2018
- Study start18 Jul 2017
- Primary completion31 Mar 2018 (estimated)
- Study completion31 Mar 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Systemic SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 46 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ASST Gaetano Pini-CTO
- Sponsor type
- University, hospital or other
- Collaborators
- Società Italiana di Reumatologia
- Responsible party
- Principal investigator, Nicoletta Del Papa, ASST Gaetano Pini-CTO
- Investigators
- Nicoletta Del Papa, MD, Principal investigator, ASST Gaetano Pini-CTO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03406988
- Sponsor's protocol ID
- ID Sperimentazione 138
- Acronym
- ADUL-SSc
- Status last verified
- Jan 2018
- First submitted
- 8 Jan 2018
- Last updated
- 25 Jan 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 19420368Steen 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.
PubMed 19487218Del 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.
PubMed 25506730Del 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.
PubMed 30616671
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Regional Grafting of Autologous Adipose Tissue in the Treatment of Systemic Sclerosis Digital Ulcers: a Prospective Randomized Controlled Study
- ClinicalTrials.gov ID
- NCT03406988
- Acronym / sponsor ID
- ADUL-SSc / ID Sperimentazione 138
- Conditions
- Systemic Sclerosis, Digital Ulcer
- Keywords
- Systemic Sclerosis, Digital Ulcer, Autologous fat grafting, Adipose tissue stem cells
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 46 participants (estimated)
- Lead sponsor
- ASST Gaetano Pini-CTOUniversity, hospital or other
- Collaborators
- Società Italiana di Reumatologia
- Study start
- 18 Jul 2017 (actual)
- Primary completion
- 31 Mar 2018 (estimated)
- Study completion
- 31 Mar 2018 (estimated)
- First posted
- 23 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Autologous fat grafting | Experimental | Procedure: Autologous fat graftingImplantation of 0.5-1 ml of autologous AT at the base of the finger with DU. |
| Sham procedure | Placebo comparator | Procedure: Sham procedureFalse liposuction followed by the injection of 0.5-1 ml of 0.9% saline solution at the base of the affected finger. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autologous fat graftingAlso: Iloprost infusion, oral nifedipineImplantation of small amount of autologous adipose tissue at the base of the finger to induce a rapid healing of the distally located DU | Procedure or surgery | Autologous fat grafting |
| Sham procedureAlso: Iloprost infusion, oral nifedipineLocal injection of 0.5ml saline solution after a simulated liposuction procedure. | Procedure or surgery | Sham procedure |
Primary outcome
Digital Ulcer healing
Time frame: 8 weeks after either autologus fat grafting or sham procedure.
Prevalence of DU healing in the arm treated with autologous fat grafting in comparison with the prevalence of healing in the placebo group.
2 secondary outcomes
Pain evaluation by Visual Analogue Scale (VAS)
Time frame: 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
Time frame: Baseline and 8 weeks after either autologus fat grafting or sham procedure.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2018.
- Background: PubMed 19420368Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. N Engl J Med. 2009 May 7;360(19):1989-2003. doi: 10.1056/NEJMra0806188. No abstract available.
- Background: PubMed 19487218Steen 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.
- Background: PubMed 25506730Del 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.
- Derived from this study: PubMed 30616671Del 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.
- Individual participant dataSharing planned: No
Related trials for Systemic Sclerosis
Not yet recruitingPhase 2
Hyaluronidase Injections for Sclerodactyly in Patients With Scleroderma
Scleroderma, Sclerodactyly
RecruitingPhase 1
A Trial in Healthy Adult Participants and Adults With Autoimmune Diseases to Test How HBM7020 is Tolerated and How it Behaves in the Body
Rheumatoid Arthritis, Systemic Lupus Erythematosus
Active, not recruitingPhase 2
A Study Evaluating the Safety and Efficacy of Inhaled AP01 in Participants With Progressive Pulmonary Fibrosis
Pulmonary Fibrosis, Progressive Pulmonary Fibrosis
RecruitingObservational study
Quantification of Calcinosis Cutis Disease Burden Using Computed Tomography Images
Systemic Sclerosis (SSc), Calcinosis Cutis
RecruitingPhase 1/2
Phase I/II Study of AD-PluReceptor Plus Tafasitamab-cxix and Lymphodepleting Chemotherapy in Patients With Autoimmune Disorders
Autoimmune Disorders, Systemic Sclerosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicoletta Del Papa, MD principal investigator
ASST Gaetano Pini-CTO
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Autologous fat grafting in people with Systemic Sclerosis and Digital Ulcer, run by ASST Gaetano Pini-CTO at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nicoletta Del Papa, MD (+39-0258296415, nicoletta.delpapa@asst-pini-cto.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Digital Ulcer healing (time frame: 8 weeks after either autologus fat grafting or sham procedure.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03406988, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jan 2018.