Subcutaneous Injections of ASC to Heal Digital Ulcers in Patients With Scleroderma. (ADUSE)

December 23, 2025 updated by: University Hospital, Toulouse

Subcutaneous Injections of Cultured Adipose-derived Stroma/ Stem Cells to Heal Refractory Ischemic Digital Ulcers in Patients With Scleroderma

Ischemic digital ulcers (DUs) are a frequent complication in systemic sclerosis with a major impact on hand function and quality of life. Digital injection of cultured adipose-derived stromal cell (AdMSC) constitutes a promising approach to treat scleroderma-induced refractory ischemic DUs where no alternative therapy is validated. The aim of this phase 2 study is to compare efficacy and safety of digital injection of AdMSC versus placebo for healing refractory active ischemic digital ulcers in patients with systemic sclerosis.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by an autoimmune-mediated microangiopathy and progressive fibrosis. Ischemic digital ulcers (DUs) are frequent in the disease course. DUs are an expression of the severity of the microangiopathy. DUs lead to pain, infection, gangrene, autoamputation, impaired hand use and impaired quality of life. The management of DUs is often based on optimal wound care to promote healing and and repeated hospitalizations to perform onerous prostacyclin infusions to reduce pain and accelerate healing. With optimal standard of care, only 60% of DUs are healed after 3 months and 46.2% experiences recurrence during that time among them 11.2% experiences a chronic evolution. No drug has demonstrated a positive effect on refractory DUs healing. The rational underlying the use of cultured adipose-derived stromal cell (AdMSC) in this indication is based on the finding of AdMSC, in vitro and in vivo, angiogenic and anti-inflammatory potential in other ischemic pathologies, with an excellent safety profile. The pilot phase of the ACellDREAM trial demonstrated the feasibility and safety of AdMSC transplantation in patients with non- revascularizable critical limb ischemia and showed improvement in ulcer evolution and wound healing. The EFS-O culture procedure safety is validated and is already in use in ongoing French and European clinical trials. Two pilot studies showed the safety of adipose tissue grafting for scleroderma-Induced DU. The SCLERADEC pilot study outlines the safety, in 12 SSc patients, of the digital injection of adipose- derived stromal vascular fraction, which is a heterogeneous population of cells including only 36% of uncultured AdMSC. An improvement in hand disability, quality of life and DUs was observed, the phase II is ongoing. The hypothesis of the study is that digital injection of AdMSC could be efficacious for scleroderma-induced refractory ischemic DUs healing by digital vascular regeneration in a clinical situation where no alternative therapy is validated.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
32

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • France
      • Grenoble, France
        • Not yet recruiting
        • Grenoble Hospital
        • Contact:
          • Bernard IMBERT
      • Lille, France
        • Not yet recruiting
        • Lille Hopsital
        • Contact:
          • Eric Hachulla
      • Marseille, France
        • Not yet recruiting
        • Marseille Hospital
        • Contact:
          • Brigitte Granel
      • Montpellier, France
        • Not yet recruiting
        • Montpellier Hospital
        • Contact:
          • Philippe GILPAIN
      • Nantes, France
        • Not yet recruiting
        • Nantes Hospital
        • Contact:
          • Christian AGARD
      • Poitiers, France
        • Not yet recruiting
        • Poitiers Hospital
        • Contact:
          • Mathieu Puyade
      • Toulouse, France, 31059
        • Recruiting
        • CHU de Toulouse - Hôpital PURPAN-TSA
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Male or female patient ≥18 years of age,
  • Patient with systemic sclerosis according to the 2013 ACR/EULAR classification criteria9,
  • SSc patient with at least one refractory active ischemic digital ulcer at "inclusion visit" (see below the eligibility conditions of a DU),
  • Age > 50 years and not treated with any kind of hormone replacement therapy for at least 2 years prior to screening, with amenorrhea for at least 24 consecutive months prior to screening. An assessment of serum follicle stimulating hormone showing a level of > 40 TU/L at screening may be used to exclude childbearing potential, based on the discretion of the investigator,
  • Patient must have provided written informed consent prior to enrolment,
  • Patient must be able to understand their requirements of participating in the protocol,
  • Patient affiliated to a social security system.
  • Relative to each DU :

The DU at " inclusion visit " must show all the following characteristics:

  1. Located beyond the proximal interphalangeal joint, on finger surface (included periungual ulcers),
  2. Of ischemic origin according to the physician,
  3. Not over subcutaneous calcifications or bone relief,
  4. Active DU,
  5. Refractory after 10±2 weeks of standard of care according to EULAR recommendations26 (that is either still active (chronic) or new occurrence despite standard of care)

Exclusion Criteria:

  • Current smoker or tobacco consumption stopped for less than 3 months prior to inclusion, - Patient participating in a clinical trial or having participated in a clinical trial within the previous 3 months,
  • Patients on statins, who have received treatment for less than 3 months prior to Screening or whose treatment has not been stable during this period,
  • Patients on vasodilators, such as endothelin receptor antagonists (ERAs), PDE5 inhibitors (e.g. sildenafil, tadalafil), calcium channel blockers, ACE-inhibitors, nitroglycerin, alpha adrenergic blockers, or angiotensin II receptor antagonists, N-acetylcysteine, antiplatelet aggregation therapy and low molecular weight heparin who have received treatment if present for less than 3 months prior to "inclusion visit" or whose treatment has not been stable for at least 1 month prior to "inclusion visit",
  • Treatment with disease modifying agents such as methotrexate, mycophenolate mofetil, azathioprine, tacrolimus, Interferons and cyclophosphamide, those drugs should be stop at least 1 month prior study entry.
  • Treatment with oral corticosteroids (> 10 mg/day of prednisone or equivalent),
  • Systemic antibiotics (oral and TV) to treat infected DU(s) within 4 weeks prior to "inclusion visit",
  • Use of topical growth factors, hyperbaric oxygen,
  • Local injection of botulinum toxin in an affected finger within 4 weeks prior to "inclusion visit",
  • Surgical sympathectomy of the upper limbs or surgical wound debridement within 1 month prior to "inclusion visit",
  • Liposuction technically impossible,
  • Patient who underwent autologous hematopoietic stem cell transplantation (HSCT) within less than 1 year,
  • Patients with an indication for intensification by autologous HSCT (according to EBMT guidelines and national RCP MATHEC),
  • History of cancer in the last five years, except for successfully excised basal cell/squamous cell carcinoma, or successfully excised early melanoma of the skin. Subjects, who had successfully tumor resection or radiation or chemotherapy more than 5 years from inclusion and no recurrence, may be enrolled in the study, - Subjects who have active proliferative retinopathy,
  • Positive HIV-1 or 2, HTLV-1 or 2, HBV or HCV,
  • Patients with a history of stroke, myocardial infarction or severe arrhythmia in the last 6 months
  • Patient who had severe cardiac failure in the last 6 months,
  • Females who are pregnant or breastfeeding or plan to do so during the course of this study,
  • Patient under judicial protection, - Refusal of the patient to participate in the study.

  • Relative to each DU:

    1. Digital ulcer due to conditions other than scleroderma,
    2. Non ischemic digital ulcer,
    3. Ulcers with osteomyelitis, or clinically uncontrolled infection,
    4. Infected digital ulcer requiring systemic antibiotherapy,
    5. Digital ulcer requiring urgent surgery.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Subcutaneous injections of placebo comparator to heal refractory ischemic digital ulcers in patients with scleroderma
Drug: Placebo
At day 0, patients will have placebo injections in their ischemic DU. Patients will be followed-up for 16 weeks
Experimental: AdMSC
Subcutaneous injections of cultured adipose-derived stroma/stem cells to heal refractory ischemic digital ulcers in patients with scleroderma
Drug: AdMSC
At day 0, patients will have AdMSC injections in their ischemic DU. Patients will be followed-up for 16 weeks

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Proportion of refractory active ischemic digital ulcers healed (complete or partial)
Time Frame: 16 weeks
Partial healing is defined as > 50% reduction of the DU area or > 50% re epidermisation of the DU.
16 weeks
Composite endpoint combining healing (complete or partial) without recurrence and without local or general complications
Time Frame: 16 weeks

Partial healing is defined as > 50% reduction of the DU area or > 50% re epidermisation of the DU.

Local complications resulting from DU worsening:

  • Critical ischemic crisis necessitating hospitalization,
  • Gangrene, (auto) amputation,
  • Failure of conservative management: Surgical and chemical sympathectomy, vascular reconstructions, or any unplanned surgery in the management of hand SSc manifestation(s),
  • Use of parenteral prostanoids after treatment injection,
  • Requiring class II, III or IV narcotics or increase in existing dose of > 50 % as compared to baseline,
  • Initiation of systemic antibiotics for the treatment of infection attributed to digital ulceration.

General complications will be assessed by:

  • Clinical examination
  • Patient reported-outcomes
  • Laboratory assessments
16 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of participants with Digital Ulcer complete healing
Time Frame: 16 weeks
Number of complete ulcer Healing. Complete healing is defined as 100% re-epidermisation.
16 weeks
Percentage of participants with Digital Ulcer partial healing
Time Frame: 16 weeks
Number of partial ulcer Healing. Partial healing is defined as > 50% reduction of the DU area or > 50% re epidermisation of the DU.
16 weeks
Percentage of participants with wound surface reduction <50%
Time Frame: 16 weeks
the wound surface reduction is defined by analysis photography
16 weeks
Percentage of participants with new Digital Ulcer
Time Frame: 16 weeks
Number of patients who do not develop any new DU.
16 weeks
Percentage of participants with Digital Ulcer complication
Time Frame: 16 weeks
A complication is an infection, gangrene, amputation or a DU requiring IV prostanoids.
16 weeks
Change from Baseline in Pain Scores
Time Frame: 16 weeks
Evaluation of pain on a Visual Analog Scale. The visual scale measures the intensity of pain on a scale ranging from 0 (no pain) to 10 (maximum pain).
16 weeks
Change from Baseline in severity of Raynaud's phenomenon
Time Frame: 16 weeks
Change in severity of Raynaud's phenomenon on a Visual Analog Scale. The visual scale is in a form of plastic ruler and measures the severity of Raynaud's phenomenon on a scale ranging from 0 (no pain) to 100 (maximum pain).
16 weeks
Change from Baseline in Digital ischaemia
Time Frame: 16 weeks
Change in digital ischaemia of the treated fingers on Digital arterial pressure.
16 weeks
Change from Baseline in cutaneous ischaemia
Time Frame: 16 weeks
Change in cutaneous ischaemia of the treated fingers on transcutaneous oxygen pressure (TcPO2).
16 weeks
Change from Baseline in Digital microvascular organisation
Time Frame: 16 weeks
Change in digital microvascular organisation of the treated fingers on nailfold capillaroscopy.
16 weeks
Change from Baseline in hand functional disability
Time Frame: 16 weeks
Evaluation of hand functional disability by the Cochin Hand Function Scale.
16 weeks
Change from Baseline in quality of life in systemic sclerosis
Time Frame: 16 weeks
Evaluation of quality of life in systemic sclerosis by scleroderma health assesment (SHAQ).
16 weeks
Change from Baseline in quality of life
Time Frame: 16 weeks
Evaluation of quality of life by the SF36.
16 weeks
Change from Baseline in health status
Time Frame: 16 weeks
Evaluation of health status by the EQ5D.
16 weeks
Vascular biomarkers
Time Frame: 16 weeks
Endothelin-1, Endostatin, Endogline, Angiotensin I and II, Tie 1 and 2, V-EGF, sICAM-1, sVCAM, E-selectin, CXCL4 plus anti-AT1R, anti-ETAR, anti Annexin V will be measured out in blood samples by Luminex
16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital, Toulouse

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Grégory PUGNET, MD, PHD

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 22, 2020

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 11, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 17, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 22, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 31, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 23, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RC31/17/0447

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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