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

Scleroderma, Diffuse Clinical Trial

Official title:

Rare Disease With Microvascular Involvement: High Dose Intravenous N-Acetylcysteine Versus Iloprost for Early, Rapidly Progressive Diffuse Systemic Sclerosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00428883
• Other study ID #: FARM5X8AWM
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: January 29, 2007
• Last updated: January 29, 2007
• Start date: January 2007
• Est. completion date: February 2009

Study information

• Verified date: January 2007
• Source: Università Politecnica delle Marche
• Contact: Armando Gabrielli, MD,Professor
• Phone: +390712206101
• Email: a.gabrielli[@]univpm.it
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Scleroderma, Diffuse
• Scleroderma, Systemic

Intervention

Drug:
• N-acetylcysteine (NAC)

Locations

Country	Name	City	State
Italy	Università politecnica delle marche	Ancona
Italy	Università de L’Aquila	Aquila
Italy	Università di Firenze	Firenze
Italy	Seconda Università di Napoli	Napoli
Italy	Catholic University of the Sacred	Roma

Sponsors (1)

Lead Sponsor	Collaborator
Università Politecnica delle Marche

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary outcome is the reduction of skin thickness
Primary	Evaluated by the modified Rodnan skin score.
Secondary	scleroderma disease activity assessed as established
Secondary	patient physical and emotional well-being (VAS, HAQ, SF36)
Secondary	laboratory evidence of skin fibroblast activation;
Secondary	the levels of Glutathione and of oxidized glutathione (GSSG).