This study has been transitioned to CTIS with ID 2024-515387-31-00 check the CTIS register for the current data. To investigate whether in patients with peripheral vascular complications related to SSc, intramuscular allogeneic BM-MSC therapy is…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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 outcome
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.
Background summary
Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis and
vasculopathy. Clinical features of vasculopathy are common and severe in
patients with SSc. Digital ischemia is a frequent manifestation, which may lead
to digital ulcers or acrolysis and tissue loss, infection, gangrene, amputation
and septicaemia. Despite recent advances in pharmacological treatments there is
currently no way to promote ulcer healing. New treatments are urgently needed.
Mesenchymal stem or stromal cells (MSC), because of their immunomodulatory and
vasculoregenerative properties, may provide a novel therapy for peripheral
ischemia in SSc. Allogeneic MSC therapy is attractive as it involves
functionally competent MSC from healthy donors and may be used as *off-
the-shelf* available treatment.
Study objective
This study has been transitioned to CTIS with ID 2024-515387-31-00 check the CTIS register for the current data.
To investigate whether in patients with peripheral vascular complications
related to SSc, intramuscular allogeneic BM-MSC therapy is feasible, safe and
potentially effective. We expect that the proposed trial will allow us to come
to a go-no go decision to proceed with a large multicenter study with longer
follow-up within 2 years. In this follow-up trial, we also intend to further
elucidate the mechanism of action of MSCs.
Study design
A randomized double-blind, placebo-controlled clinical trial.
Intervention
Patients are randomised (1:1) to intramuscular injection (8 sites) of
allogeneic BM-MSC (50*10^6) or placebo in the ischemic limb.
Study burden and risks
Subjects will be screened in a baseline visit, where they will be physically
examined and blood samples will be taken (40mL). An appointment for the
treatment will be made. Consequently, there are 7 follow-up visits. Follow-up
visits include physical examination and documenting of the ulcers.
Questionnaires will be administered at baseline and at visit 5, 6 and 7. During
the trial, the patients are subjected to venepuncture five times during which
40mL blood will be taken. Skin biopsies will be taken twice. Capillaroscopy (a
non painful exam) will be performed at five visits.
In previous trials allogeneic MSC administration was not associated with
serious adverse events and are well tolerated.
Heidelberglaan 100
Utrecht 3584CX
NL
Heidelberglaan 100
Utrecht 3584CX
NL
Listed location countries
Age
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
- 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 <1 year
- Uncontrolled hypertension
- Uncontrolled acute or chronic infection
- Follow-up impossible
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-515387-31-00 |
| EudraCT | EUCTR2015-000168-32-NL |
| CCMO | NL51705.000.15 |