Hit hard and early

• Register: EUCTR
• Last refreshed on: 13 June 2016
• Main ID: EUCTR2015-004613-24-NL
• Date of registration: 13/04/2016
• Prospective Registration: Yes
• Primary sponsor: Radboudumc
• Public title: Hit hard and early
• Scientific title: Hit hard and early. The effect of high dose methylprednisolon on nailfold capillary changes and biomarkers in early SSc: a 12-week randomized double-blind placebo-controlled trial. - Hit hard and early
• Date of first enrolment: 30/05/2016
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-004613-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Netherlands

Contacts

• Name: Franka Hoeks-van Dinther
• Affiliation: Radboudumc

• Name: Franka Hoeks-van Dinther
• Affiliation: Radboudumc

Key inclusion & exclusion criteria

Inclusion criteria:
- Age = 18 years
- Fulfilling VEDOSS criteria:
• Raynauds’ Phenomenon and
• Positive for disease specific auto antibodies (anti-centromere or anti-topoisomerase antibodies) and
• Systemic sclerosis specific nail fold capillaroscopic findings
- Puffy fingers < 3 years duration
- modified Rodnan Skin Score =0
- Written informed consent

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
- Presence of acrosclerosis, 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), mofetyl mycophenolate and cyclophosphamide.
- Clinically significant internal organ involvement: DLCO< 80% predicted, VC < 70% predicted, renal dysfunction with 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) or acute infections.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

(very early) systemic sclerosis

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: methylprednisolon
Pharmaceutical Form: Concentrate and solvent for solution for infusion
INN or Proposed INN: methylprednisolon
Other descriptive name: METHYLPREDNISOLONE SODIUM SUCCINATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1000-
Pharmaceutical form of the placebo: Concentrate and solvent for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 12 weeks

Primary end point(s): In this study, the primary endpoint will be the change in capillary density between baseline and 12 weeks.

Secondary Objective: To investigate the effects of glucocorticoids on signs and symptoms of disease progression.

To analyze the effect of glucocorticoids on inflammatory biomarkers that have been implicated in SSc pathogenesis

Main Objective: To evaluate the changes of high dose intravenous methylprednisolone on nail fold capillaries as measured by nail fold capillary microscopy (NCM) at week 12

Secondary Outcome(s)

Secondary end point(s): The secondary outcomes of this study are: (all compared between baseline and week 12 and between baseline and 1 year) change in selected biomarkers: the interferon signature in peripheral blood cells CXCL4, IL-1ß, IL-6, TNF-a, ET-1, ICAM-1 and VEGF; change in nail fold capillary changes other than capillary density and giant capillaries; changes in nail fold capillary pattern (early, active, late, normal); change in modified Rodnan skin score; presence of puffy fingers; presence of synovitis, presence of tendon friction rubs; fulfilling EULAR/ACR classification criteria for SSc (24), pulmonary function tests; presence of interstitial lung disease; suspicion of PH; and physical function, general health and utilities as measured by the SHAQ, SF-36, EQ5D and GIT.

Timepoint(s) of evaluation of this end point: 12 months

Source(s) of Monetary Support

Radboudumc