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.
试验速览
- 阶段
- 早期 1 期
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- the change in capillary density from baseline
研究概览
简要总结
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
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Methylprednisolone 1000 mg
the methylprednisolone is dissolved in 100 cc of sodium chloride (NaCl 0.9%) by intravenous infusion in 30 minutes on three consecutive days
干预措施: Methylprednisolone (Drug)
sodium chloride
The placebo intervention with physiologic salt solution is identical in appearance
干预措施: sodium chloride (Other)
结局指标
主要结局
the change in capillary density from baseline
时间窗: 12 weeks
presence of enlarged and giant capillaries, hemorrhages, loss of capillaries, disorganization of the micro vascular array, and capillary ramifications.
次要结局
- presence of interstitial lung disease from baseline(1 year)
- suspicion of pulmonary hypertension from baseline(1 year)
- Change in physical function from baseline(1 year)
- presence of synovitis from baseline(1 year)
- presence of tendon friction rubs from baseline(1 year)
- pulmonary function tests from baseline(1 year)
- change in selected biomarkers: the interferon signature in peripheral blood from baseline(1 year)
- change in nail fold capillary changes other than capillary density and giant capillaries from baseline(1 year)
- change in modified Rodnan skin score (mRSS) from baseline(1 year)
- presence of puffy fingers from baseline(1 year)
- fulfilling EULAR/ACR ( American College of Rheumatology )classification from baseline criteria for SSc from baseline(1 year)
- general health score from baseline(1 year)
- Change in Scleroderma Health Assessment Questionnaire (SHAQ)total score from baseline(1 year)
- Change in EQ-5D is a standardised instrument for use as a measure of health outcome. (EQ5D) total score from baseline(1 year)
- Change in gastrointestinal tract ( GIT ) total score from baseline(1 year)
- Change in 36-Item Short Form Survey (SF-36) total score from baseline(1 year)