Clinical trial NCT03059979: The Effect of High Dose Methylprednisolone on Nailfold in Early Systemic Sclerosis ( SSc )
Official title: Hit Hard and Early. The Effect of High Dose Methylprednisolone on Nailfold Capillary Changes and Biomarkers in Early SSc: a 12-week Randomised Explorative Double-blind Placebo-controlled Trial.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Systemic Sclerosis
Raynaud Phenomena
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2017-02-23
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a 12 week double-blind randomized placebo controlled trial in which 30 patients with very early SSc, fulfilling the Very Early Diagnosis Of Systemic Sclerosis (VEDOSS) criteria (9) will be randomized in a 2:1 fashion to receive intravenous methylprednisolone or placebo. Three-day treatment courses are given at week 0, week 4 and week 8. The final assessment is at week 12, and patients will be followed up to one year after baseline

Detailed description: Systemic sclerosis is a disease with a high burden caused by morbidity and increased mortality. To date a cure for SSc is not available. In this trial, patients are treated very early in the disease which could change the long term outcome of SSc in these patients.

In daily practice, patients so early in the disease course are not treated although they might be at risk for early escalation and internal organ involvement, reducing their prognosis. A trial to investigate the efficacy of a relative save, inexpensive and easy accessible treatment will provide us with the opportunity to change the disease course and reducing the disease burden of a portion of the SSc patients

Eligibility criteria: Inclusion Criteria:

* Written informed consent
* Age over 18 years
* Fulfilling VEDOSS criteria (9):

  * Raynauds' Phenomenon and
  * Positive for disease specific auto antibodies (anti-centromere or anti-topoisomerase antibodies) and
  * typical nail fold capillaroscopic findings
* Puffy fingers \< 3 years
* Modified Rodnan skin score = 0

Exclusion Criteria:

* Presence of acroosclerosis, acrosteolysis and digital ulcers
* Presence of anti-RNA polymerase III auto antibodies

Previous systemic treatment for SSc, namely:

* methotrexate,
* prednisone (\> 14 days in previous 6 months),
* mofetil mycophenolate
* cyclophosphamide.

Clinically significant internal organ involvement:

* diffusion capacity of lung for carbon monoxide (DLCO) \< 80% predicted,
* vital capacity (VC) \< 70% predicted
* renal dysfunction with glomerular filtration rate (GFR) \< 60 ml/min
* diastolic dysfunction \> grade 1 on echocardiography
* pulmonary hypertension
* weight loss \>10% in the last 6 months with unknown cause

Contra-indications for methylprednisolone, such as:

* pregnancy, lactation
* psychotic or depressive disorder
* ulcus duodeni or ventriculi
* untreated hypertension (\> 160-90 mmHg)
* acute infections

Primary outcomes:
measure: the change in capillary density from baseline
timeFrame: 12 weeks
Secondary outcomes:
measure: change in selected biomarkers: the interferon signature in peripheral blood from baseline
timeFrame: 1 year
measure: change in nail fold capillary changes other than capillary density and giant capillaries from baseline
timeFrame: 1 year
measure: change in modified Rodnan skin score (mRSS) from baseline
timeFrame: 1 year
measure: presence of puffy fingers from baseline
timeFrame: 1 year
measure: presence of synovitis from baseline
timeFrame: 1 year
measure: presence of tendon friction rubs from baseline
timeFrame: 1 year
measure: fulfilling EULAR/ACR ( American College of Rheumatology )classification from baseline criteria for SSc from baseline
timeFrame: 1 year
measure: pulmonary function tests from baseline
timeFrame: 1 year
measure: presence of interstitial lung disease from baseline
timeFrame: 1 year
measure: suspicion of pulmonary hypertension from baseline
timeFrame: 1 year
measure: Change in physical function from baseline
timeFrame: 1 year
measure: general health score from baseline
timeFrame: 1 year
measure: Change in 36-Item Short Form Survey (SF-36) total score from baseline
timeFrame: 1 year
measure: Change in Scleroderma Health Assessment Questionnaire (SHAQ)total score from baseline
timeFrame: 1 year
measure: Change in EQ-5D is a standardised instrument for use as a measure of health outcome. (EQ5D) total score from baseline
timeFrame: 1 year
measure: Change in gastrointestinal tract ( GIT ) total score from baseline
timeFrame: 1 year
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboudumc, Rheumatology department
state: Gelderland
Study officials:
affiliation: Radboud University Medical Center
name: Madelon Vonk, Dr.
role: PRINCIPAL_INVESTIGATOR
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