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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03059979
Recruitment Status : Recruiting
First Posted : February 23, 2017
Last Update Posted : November 29, 2019
Information provided by (Responsible Party):
Radboud University

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

Condition or disease Intervention/treatment Phase
Systemic Sclerosis Raynaud Phenomena Drug: Methylprednisolone Other: sodium chloride Early Phase 1

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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 Start Date : January 2017
Estimated Primary Completion Date : July 1, 2021
Estimated Study Completion Date : July 1, 2021

Arm Intervention/treatment
Active Comparator: 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
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 Name: Solu-Medrol

Placebo Comparator: sodium chloride
The placebo intervention with physiologic salt solution is identical in appearance
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.
Other Name: NaCl 0,9%

Primary Outcome Measures :
  1. the change in capillary density from baseline [ Time Frame: 12 weeks ]
    presence of enlarged and giant capillaries, hemorrhages, loss of capillaries, disorganization of the micro vascular array, and capillary ramifications.

Secondary Outcome Measures :
  1. change in selected biomarkers: the interferon signature in peripheral blood from baseline [ Time Frame: 1 year ]
    Plasma biomarkers consist soluble inflammatory mediators platelet factor 4, interleukin-1β, interleukin-6, tumor necrosis factor-α, endothelin-1, intercellular adhesion molecule-1 and vascular endothelial growth factor

  2. change in nail fold capillary changes other than capillary density and giant capillaries from baseline [ Time Frame: 1 year ]
    changes in nail fold capillary pattern (early, active, late, normal

  3. change in modified Rodnan skin score (mRSS) from baseline [ Time Frame: 1 year ]
  4. presence of puffy fingers from baseline [ Time Frame: 1 year ]
  5. presence of synovitis from baseline [ Time Frame: 1 year ]
  6. presence of tendon friction rubs from baseline [ Time Frame: 1 year ]
  7. fulfilling EULAR/ACR ( American College of Rheumatology )classification from baseline criteria for SSc from baseline [ Time Frame: 1 year ]
  8. pulmonary function tests from baseline [ Time Frame: 1 year ]
  9. presence of interstitial lung disease from baseline [ Time Frame: 1 year ]
  10. suspicion of pulmonary hypertension from baseline [ Time Frame: 1 year ]
  11. Change in physical function from baseline [ Time Frame: 1 year ]
  12. general health score from baseline [ Time Frame: 1 year ]
  13. Change in 36-Item Short Form Survey (SF-36) total score from baseline [ Time Frame: 1 year ]
  14. Change in Scleroderma Health Assessment Questionnaire (SHAQ)total score from baseline [ Time Frame: 1 year ]
  15. Change in EQ-5D is a standardised instrument for use as a measure of health outcome. (EQ5D) total score from baseline [ Time Frame: 1 year ]
  16. Change in gastrointestinal tract ( GIT ) total score from baseline [ Time Frame: 1 year ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03059979

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Contact: Sjoukje Mulder +31 24 3619398
Contact: Brigit Kersten +31 24 361 4580

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Radboudumc, Rheumatology department Recruiting
Nijmegen, Gelderland, Netherlands, 6500 HB
Contact: Sjoukje Mulder    +31 24 3619398   
Contact: Brigit Kersten   
Sub-Investigator: Brigit Kersten         
Principal Investigator: Madelon Vonk         
Sponsors and Collaborators
Radboud University
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Principal Investigator: Madelon Vonk, Dr. Radboud University
Radstake TR, Gorlova O, Rueda B, Martin JE, Alizadeh BZ, Palomino-Morales R, Coenen MJ, Vonk MC, Voskuyl AE, Schuerwegh AJ, Broen JC, van Riel PL, van 't Slot R, Italiaander A, Ophoff RA, Riemekasten G, Hunzelmann N, Simeon CP, Ortego-Centeno N, González-Gay MA, González-Escribano MF; Spanish Scleroderma Group, Airo P, van Laar J, Herrick A, Worthington J, Hesselstrand R, Smith V, de Keyser F, Houssiau F, Chee MM, Madhok R, Shiels P, Westhovens R, Kreuter A, Kiener H, de Baere E, Witte T, Padykov L, Klareskog L, Beretta L, Scorza R, Lie BA, Hoffmann-Vold AM, Carreira P, Varga J, Hinchcliff M, Gregersen PK, Lee AT, Ying J, Han Y, Weng SF, Amos CI, Wigley FM, Hummers L, Nelson JL, Agarwal SK, Assassi S, Gourh P, Tan FK, Koeleman BP, Arnett FC, Martin J, Mayes MD. Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus. Nat Genet. 2010 May;42(5):426-9. doi: 10.1038/ng.565. Epub 2010 Apr 11.
van Laar JM, Farge D, Sont JK, Naraghi K, Marjanovic Z, Larghero J, Schuerwegh AJ, Marijt EW, Vonk MC, Schattenberg AV, Matucci-Cerinic M, Voskuyl AE, van de Loosdrecht AA, Daikeler T, Kötter I, Schmalzing M, Martin T, Lioure B, Weiner SM, Kreuter A, Deligny C, Durand JM, Emery P, Machold KP, Sarrot-Reynauld F, Warnatz K, Adoue DF, Constans J, Tony HP, Del Papa N, Fassas A, Himsel A, Launay D, Lo Monaco A, Philippe P, Quéré I, Rich É, Westhovens R, Griffiths B, Saccardi R, van den Hoogen FH, Fibbe WE, Socié G, Gratwohl A, Tyndall A; EBMT/EULAR Scleroderma Study Group. Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial. JAMA. 2014 Jun 25;311(24):2490-8. doi: 10.1001/jama.2014.6368.

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Radboud University Identifier: NCT03059979    
Other Study ID Numbers: HHaE
First Posted: February 23, 2017    Key Record Dates
Last Update Posted: November 29, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Additional relevant MeSH terms:
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Raynaud Disease
Scleroderma, Systemic
Scleroderma, Diffuse
Pathologic Processes
Connective Tissue Diseases
Skin Diseases
Peripheral Vascular Diseases
Vascular Diseases
Cardiovascular Diseases
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Protective Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents