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Systemic SclerosisEarly Phase 1NCT03059979

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

A Early Phase 1 study testing Methylprednisolone and sodium chloride in people with Systemic Sclerosis and Raynaud Phenomena, run by Radboud University Medical Center at 1 site in Netherlands.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Systemic Sclerosis, Raynaud Phenomena
What is being tested?
Methylprednisolone and sodium chloride
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
30 participants
Where
1 siteNetherlands
Study dates
Jan 2017to 1 Jul 2021
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 20Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Brigit Kersten contact

+31 24 361 4580

Netherlands1 site, 1 recruiting
  • Radboudumc, Rheumatology department

    Nijmegen, Gelderland, 6500 HB

    Sjoukje Mulder, +31 24 3619398, sjoukje.mulder@radboudumc.nl

    Brigit Kersten, B.Kersten@radboudumc.nl

    Recruiting

Other trials in Netherlands

About this study

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.

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

Read the 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

Being tested
Methylprednisolone, sodium chloride
Medical subject headings
Scleroderma, Systemic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MethylprednisoloneDrug

    Also called Solu-Medrol

    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.

  • sodium chlorideOther

    Also called NaCl 0,9%

    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.

Study groups in NCT03059979
Study groupRoleWhat they receive
Methylprednisolone 1000 mgActive comparatorthe methylprednisolone is dissolved in 100 cc of sodium chloride (NaCl 0.9%) by intravenous infusion in 30 minutes on three consecutive days
Receives: Drug: Methylprednisolone
sodium chloridePlacebo comparatorThe placebo intervention with physiologic salt solution is identical in appearance
Receives: Other: sodium chloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 12 weeks

Secondary outcomes (16)
  1. change in selected biomarkers: the interferon signature in peripheral blood from baseline

    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

    Measured: 1 year

  2. 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

    Measured: 1 year

  3. change in modified Rodnan skin score (mRSS) from baseline

    Measured: 1 year

  4. presence of puffy fingers from baseline

    Measured: 1 year

  5. presence of synovitis from baseline

    Measured: 1 year

  6. presence of tendon friction rubs from baseline

    Measured: 1 year

  7. fulfilling EULAR/ACR ( American College of Rheumatology )classification from baseline criteria for SSc from baseline

    Measured: 1 year

  8. pulmonary function tests from baseline

    Measured: 1 year

  9. presence of interstitial lung disease from baseline

    Measured: 1 year

  10. suspicion of pulmonary hypertension from baseline

    Measured: 1 year

  11. Change in physical function from baseline

    Measured: 1 year

  12. general health score from baseline

    Measured: 1 year

  13. Change in 36-Item Short Form Survey (SF-36) total score from baseline

    Measured: 1 year

  14. Change in Scleroderma Health Assessment Questionnaire (SHAQ)total score from baseline

    Measured: 1 year

  15. Change in EQ-5D is a standardised instrument for use as a measure of health outcome. (EQ5D) total score from baseline

    Measured: 1 year

  16. Change in gastrointestinal tract ( GIT ) total score from baseline

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Feb 2017
  2. Study startJan 2017
  3. Primary completion1 Jul 2021 (estimated)
  4. Study completion1 Jul 2021 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03059979
Sponsor's protocol ID
HHaE
Status last verified
Sep 2019
First submitted
25 Jan 2017
Last updated
29 Nov 2019
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • Geyer M, Muller-Ladner U. The pathogenesis of systemic sclerosis revisited. Clin Rev Allergy Immunol. 2011 Apr;40(2):92-103. doi: 10.1007/s12016-009-8193-3.

    PubMed 20087791
  • van Bon L, Affandi AJ, Broen J, Christmann RB, Marijnissen RJ, Stawski L, Farina GA, Stifano G, Mathes AL, Cossu M, York M, Collins C, Wenink M, Huijbens R, Hesselstrand R, Saxne T, DiMarzio M, Wuttge D, Agarwal SK, Reveille JD, Assassi S, Mayes M, Deng Y, Drenth JP, de Graaf J, den Heijer M, Kallenberg CG, Bijl M, Loof A, van den Berg WB, Joosten LA, Smith V, de Keyser F, Scorza R, Lunardi C, van Riel PL, Vonk M, van Heerde W, Meller S, Homey B, Beretta L, Roest M, Trojanowska M, Lafyatis R, Radstake TR. Proteome-wide analysis and CXCL4 as a biomarker in systemic sclerosis. N Engl J Med. 2014 Jan 30;370(5):433-43. doi: 10.1056/NEJMoa1114576. Epub 2013 Dec 18.

    PubMed 24350901
  • 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, Gonzalez-Gay MA, Gonzalez-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.

    PubMed 20383147
  • Greenblatt MB, Aliprantis AO. The immune pathogenesis of scleroderma: context is everything. Curr Rheumatol Rep. 2013 Jan;15(1):297. doi: 10.1007/s11926-012-0297-8.

    PubMed 23288576
  • Tyndall AJ, Bannert B, Vonk M, Airo P, Cozzi F, Carreira PE, Bancel DF, Allanore Y, Muller-Ladner U, Distler O, Iannone F, Pellerito R, Pileckyte M, Miniati I, Ananieva L, Gurman AB, Damjanov N, Mueller A, Valentini G, Riemekasten G, Tikly M, Hummers L, Henriques MJ, Caramaschi P, Scheja A, Rozman B, Ton E, Kumanovics G, Coleiro B, Feierl E, Szucs G, Von Muhlen CA, Riccieri V, Novak S, Chizzolini C, Kotulska A, Denton C, Coelho PC, Kotter I, Simsek I, de la Pena Lefebvre PG, Hachulla E, Seibold JR, Rednic S, Stork J, Morovic-Vergles J, Walker UA. Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis. 2010 Oct;69(10):1809-15. doi: 10.1136/ard.2009.114264. Epub 2010 Jun 15.

    PubMed 20551155
  • Kowal-Bielecka O, Landewe R, Avouac J, Chwiesko S, Miniati I, Czirjak L, Clements P, Denton C, Farge D, Fligelstone K, Foldvari I, Furst DE, Muller-Ladner U, Seibold J, Silver RM, Takehara K, Toth BG, Tyndall A, Valentini G, van den Hoogen F, Wigley F, Zulian F, Matucci-Cerinic M; EUSTAR Co-Authors. EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR). Ann Rheum Dis. 2009 May;68(5):620-8. doi: 10.1136/ard.2008.096677. Epub 2009 Jan 15.

    PubMed 19147617
  • 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, Kotter 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, Quere I, Rich E, Westhovens R, Griffiths B, Saccardi R, van den Hoogen FH, Fibbe WE, Socie 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.

    PubMed 25058083
  • Czirjak L, Matucci-Cerinic M. Beyond Raynaud's phenomenon hides very early systemic sclerosis: the assessment of organ involvement is always mandatory. Rheumatology (Oxford). 2011 Feb;50(2):250-1. doi: 10.1093/rheumatology/keq374. Epub 2010 Nov 28. No abstract available.

    PubMed 21115465
  • Minier T, Guiducci S, Bellando-Randone S, Bruni C, Lepri G, Czirjak L, Distler O, Walker UA, Fransen J, Allanore Y, Denton C, Cutolo M, Tyndall A, Muller-Ladner U, Matucci-Cerinic M; EUSTAR co-workers; EUSTAR co-workers. Preliminary analysis of the very early diagnosis of systemic sclerosis (VEDOSS) EUSTAR multicentre study: evidence for puffy fingers as a pivotal sign for suspicion of systemic sclerosis. Ann Rheum Dis. 2014 Dec;73(12):2087-93. doi: 10.1136/annrheumdis-2013-203716. Epub 2013 Aug 12.

    PubMed 23940211
  • Hahn BH, Kantor OS, Osterland CK. Azathioprine plus prednisone compared with prednisone alone in the treatment of systemic lupus erythematosus. Report of a prospective controlled trial in 24 patients. Ann Intern Med. 1975 Nov;83(5):597-605. doi: 10.7326/0003-4819-83-5-597.

    PubMed 1106277
  • Marie I, Mouthon L. Therapy of polymyositis and dermatomyositis. Autoimmun Rev. 2011 Nov;11(1):6-13. doi: 10.1016/j.autrev.2011.06.007. Epub 2011 Jun 28.

    PubMed 21740984
  • Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids--new mechanisms for old drugs. N Engl J Med. 2005 Oct 20;353(16):1711-23. doi: 10.1056/NEJMra050541. No abstract available.

    PubMed 16236742
  • Iudici M, van der Goes MC, Valentini G, Bijlsma JW. Glucocorticoids in systemic sclerosis: weighing the benefits and risks - a systematic review. Clin Exp Rheumatol. 2013 Mar-Apr;31(2 Suppl 76):157-65. Epub 2013 Jul 23.

    PubMed 23910618
  • Matucci-Cerinic M, Bellando-Randone S, Lepri G, Bruni C, Guiducci S. Very early versus early disease: the evolving definition of the 'many faces' of systemic sclerosis. Ann Rheum Dis. 2013 Mar;72(3):319-21. doi: 10.1136/annrheumdis-2012-202295. Epub 2012 Nov 23. No abstract available.

    PubMed 23178210
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    PubMed 7569976

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Methylprednisolone and sodium chloride in people with Systemic Sclerosis and Raynaud Phenomena, run by Radboud University Medical Center at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 29 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Sjoukje Mulder (+31 24 3619398, sjoukje.mulder@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

the change in capillary density from baseline (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03059979, which also lists 28 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2019.

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