The Effect of High Dose Methylprednisolone on Nailfold in Early Systemic Sclerosis ( SSc )

Systemic Sclerosis Clinical Trial

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03059979
• Other study ID #: HHaE
• Status: Recruiting
• Phase: Early Phase 1
• Start date: January 2017
• Est. completion date: July 1, 2021

Study information

• Verified date: September 2019
• Source: Radboud University
• Contact: Sjoukje Mulder
• Phone: +31 24 3619398
• Email: sjoukje.mulder[@]radboudumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: July 1, 2021
• Est. primary completion date: July 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Raynaud Disease
• Raynaud Phenomena
• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Systemic Sclerosis

Intervention

Drug:
• Methylprednisolone
methylprednisolone 1000 mg dissolved in 100 cc of NaCl 0.9%, by intravenous infusion in 30 minutes on three consecutive days Three-day treatment courses are given at week 0, week 4 and week 8.

Other:
• sodium chloride
100 cc of NaCl 0,9% , administered by intravenous infusion in 30 minutes on three consecutive days Three-day treatment courses are given at week 0, week 4 and week 8.

Locations

Country	Name	City	State
Netherlands	Radboudumc, Rheumatology department	Nijmegen	Gelderland

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

References & Publications (26)

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* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the change in capillary density from baseline	presence of enlarged and giant capillaries, hemorrhages, loss of capillaries, disorganization of the micro vascular array, and capillary ramifications.	12 weeks
Secondary	change in selected biomarkers: the interferon signature in peripheral blood from baseline	Plasma biomarkers consist soluble inflammatory mediators platelet factor 4, interleukin-1ß, interleukin-6, tumor necrosis factor-a, endothelin-1, intercellular adhesion molecule-1 and vascular endothelial growth factor	1 year
Secondary	change in nail fold capillary changes other than capillary density and giant capillaries from baseline	changes in nail fold capillary pattern (early, active, late, normal	1 year
Secondary	change in modified Rodnan skin score (mRSS) from baseline		1 year
Secondary	presence of puffy fingers from baseline		1 year
Secondary	presence of synovitis from baseline		1 year
Secondary	presence of tendon friction rubs from baseline		1 year
Secondary	fulfilling EULAR/ACR ( American College of Rheumatology )classification from baseline criteria for SSc from baseline		1 year
Secondary	pulmonary function tests from baseline		1 year
Secondary	presence of interstitial lung disease from baseline		1 year
Secondary	suspicion of pulmonary hypertension from baseline		1 year
Secondary	Change in physical function from baseline		1 year
Secondary	general health score from baseline		1 year
Secondary	Change in 36-Item Short Form Survey (SF-36) total score from baseline		1 year
Secondary	Change in Scleroderma Health Assessment Questionnaire (SHAQ)total score from baseline		1 year
Secondary	Change in EQ-5D is a standardised instrument for use as a measure of health outcome. (EQ5D) total score from baseline		1 year
Secondary	Change in gastrointestinal tract ( GIT ) total score from baseline		1 year