Clinical trial NCT00428883: High Dose Intravenous N-Acetylcysteine Versus Iloprost for Early, Rapidly Progressive Diffuse Systemic Sclerosis
Official title: Rare Disease With Microvascular Involvement: High Dose Intravenous N-Acetylcysteine Versus Iloprost for Early, Rapidly Progressive Diffuse Systemic Sclerosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Scleroderma, Diffuse
Keywords: Scleroderma, Systemic
Scleroderma, Diffuse
Lead sponsor: Università Politecnica delle Marche
Sponsor class: OTHER
First posted: 2007-01-30
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: * Systemic sclerosis (scleroderma; SSc) is a rare, disfiguring systemic disorder characterized by fibrosis of the skin and visceral organs that alters every aspect of an individual life
* Although some features of scleroderma phenotype are well established and represent the hallmarks of the disease, the primary cause is not fully delineated, though both endothelial cell damage, immunological abnormalities and excessive extracellular matrix production are well-documented
* Recently, excessive oxidative stress has been implicated in the pathogenesis of scleroderma
* N-acetylcysteine (NAC) exhibits direct and indirect antioxidant properties. Its free thiol group is capable of interacting with the electrophilic groups of ROS. This interaction with ROS leads to intermediate formation of NAC thiol, with NAC disulphide as a major end product. The net result is a decrease of the concentrations of OH-, H2O2, and HOCl. In addition, NAC exerts an indirect antioxidant effect related to its role as a glutathione (GSH) precursor. It serves as a central factor in protecting against internal toxic agents.
* In view of these considerations we expect that NAC can confer substantial benefit in patients with scleroderma reducing skin fibrosis in view of its antioxidant properties, and we have decided to conduct a double blind, multicenter trial to establish whether NAC could ameliorate skin fibrosis in scleroderma patients


Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of early diffuse scleroderma
* ability to give an informed consent
* use of an acceptable method of birth control (if women in childbearing age). Pregnancy will be ruled out before study beginning.

Exclusion Criteria:

* connective tissue diseases or other autoimmune diseases other than SSc;
* history of intolerance to the study drugs;
* severe cardiac failure (NYHA \>=3 or left ventricular ejection fraction \<40%), recent (\<6 months) history of myocardial infarction; symptomatic ischemic myocardial disease, ventricular tachyarrhythmia, atrial fibrillation;
* resting PaO2 \<60mm/hg
* creatinine clearance below 90ml/h
* severe hepatic failure
* bronchial asthma h. hemorrhagic diathesis i. pregnancy or lactation

Primary outcomes:
measure: The primary outcome is the reduction of skin thickness
measure: Evaluated by the modified Rodnan skin score.
Secondary outcomes:
measure: scleroderma disease activity assessed as established
measure: patient physical and emotional well-being (VAS, HAQ, SF36)
measure: laboratory evidence of skin fibroblast activation;
measure: the levels of Glutathione and of oxidized glutathione (GSSG).
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: Università politecnica delle marche
city: Aquila
country: Italy
facility: Università de L'Aquila
city: Firenze
country: Italy
facility: Università di Firenze
city: Napoli
country: Italy
facility: Seconda Università di Napoli
city: Roma
country: Italy
facility: Catholic University of the Sacred
Study officials:
affiliation: Università Politecnica delle Marche
name: Armando Gabrielli, MD,professor
role: PRINCIPAL_INVESTIGATOR
References: