High Dose Intravenous N-Acetylcysteine Versus Iloprost for Early, Rapidly Progressive Diffuse Systemic Sclerosis

Phase 2

• Conditions: Scleroderma, Diffuse

• Registration Number: NCT00428883
• Lead Sponsor: Università Politecnica delle Marche

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

Detailed Description

Not available

Study Timeline

• Status Verified: 2007-01
• Study Start: 2007-01
• Study First Submitted: 2007-01-29
• Study First Submitted QC: 2007-01-29
• Last Update Submitted: 2007-01-29
• Study First Posted: 2007-01-30
• Last Update Posted: 2007-01-30
• Study Completion: 2009-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 45

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
The primary outcome is the reduction of skin thickness
Evaluated by the modified Rodnan skin score.

Secondary Outcome Measures

Name	Time	Method
scleroderma disease activity assessed as established
patient physical and emotional well-being (VAS, HAQ, SF36)
laboratory evidence of skin fibroblast activation;
the levels of Glutathione and of oxidized glutathione (GSSG).

Trial Locations

Locations (5)

Università di Firenze; 🇮🇹 Firenze, Italy

Seconda Università di Napoli; 🇮🇹 Napoli, Italy

Catholic University of the Sacred; 🇮🇹 Roma, Italy

Università politecnica delle marche; 🇮🇹 Ancona, Italy

Università de L'Aquila; 🇮🇹 Aquila, Italy