scleroderma Systemic scleroderma
Conditions
Interventions
Patients are randomised (1:1) to intramuscular injection (8 sites) of
allogeneic BM-MSC (50*10^6) or placebo in the ischemic limb.
Sponsors
Universitair Medisch Centrum Utrecht
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Age >18 years - Established diagnosis of SSc according to criteria of the American College of Rheumatology (2013) - At least one active digital ulcer (painful area, >2 mm in diameter with visible depth and loss of dermis) refractory to 5 days intravenous prostacyclines *Refractory to prostacyclins* is defined as * - Worsening of ulcer(s) within 1 month after prostacyclins iv * - No improvement of ulcer(s) after 2 months after prostacyclins iv, as judged by the referring physician * - Recurrence of exactly the same ulcer(s) (same location) within 3 months after prostacyclins iv, - Written informed consent
Exclusion criteria
Exclusion criteria: - Ulcer with underlying calcinosis (ruled out by X-ray prior to screening/inclusion) - History of neoplasm or malignancy in the past 10 years - Pregnancy or unwillingness to use adequate contraception during study - Serious known concomitant disease with life expectancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary outcome is the toxicity of the treatment at 12 weeks after MSC administration, defined as - Local toxicity, including signs of local inflammation (swelling, warmth, impairment of function), worsening of ulcers or new ulcers or hematomes after MSC administration - 2. Other adverse events, graded according to the Common Terminology Criteria for Adverse Events.t. | — |
Secondary
| Measure | Time frame |
|---|---|
| A secondary outcome measure for safety is the incidence (at 12 weeks post treatment) of any treatment-related serious adverse events (SAE) defined as events leading to hospitalization, death, or persistent or significant disability. Secondary outcome measures for efficacy are: pain and disability parameters; healing, time to healing and reduction of new ischemic digital ulcers; modified Rodnan skin score; Scleroderma Health Assessment Questionnaire (SHAQ) including visual analogue scales (VAS) for scleroderma-specific symptoms; Quality-of-life (SF-36, EuroQol (EQ-5D); Cochin hand function score. We will also evaluate changes in capillary morphology and architecture using capillaroscopy; biochemical parameters; markers for endothelial activation and injury, inflammation , oxidative stress, circulating endothelial cells and hematopoietic and endothelial progenitor cells, cytokines and growth factors, immunological responses. Follow-up visits will be scheduled at 48 hours and 2, 4, 8, 12, 24 and 52 weeks post-treatment. | — |
Countries
Netherlands
Outcome results
None listed