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

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

• 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

Study Overview

• Status: Unknown
• Conditions: Scleroderma, Diffuse
• Intervention / Treatment: Drug: N-acetylcysteine (NAC)

• Study Type: Interventional
• Enrollment: 45
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Armando Gabrielli, MD,Professor; Phone Number: +390712206101; Email: a.gabrielli@univpm.it
• Study Contact Backup: Name: Giovanni Pomponio, MD; Phone Number: +390715964209; Email: g.pomponio@ao-umbertoprimo.marche.it

Study Locations

• Italy
  • Ancona, Italy, 60020
    • Recruiting
    • Università Politecnica delle Marche
    • Contact: Armando Gabrielli, MD,professor; Phone Number: +390712206104; Email: a.gabrielli@univpm.it
    • Contact: Giovanni Pomponio, MD; Phone Number: +390715964205; Email: g.pomponio@ao-umbertoprimo.marche.it
    • Principal Investigator: Armando Gabrielli, MD,professor
  • Aquila, Italy
    • Recruiting
    • Università de L'Aquila
    • Contact: Roberto Giacomelli, Ph; Email: roberto.giacomelli@cc.univaq.it
    • Principal Investigator: Roberto Giacomelli, MD,professor
  • Firenze, Italy
    • Recruiting
    • Universita Di Firenze
    • Contact: Marco Matucci-Cerinic, MD,professor; Email: cerinic@unifi.it
    • Principal Investigator: Marco Matucci-Cerinic, MD,professor
  • Napoli, Italy
    • Recruiting
    • Seconda Universita di Napoli
    • Contact: Gabriele Valentini, MD,professor; Email: gabriele.valentini@unina2.it
    • Principal Investigator: Gabriele Valentini, MD,professor
  • Roma, Italy
    • Recruiting
    • Catholic University of the Sacred
    • Contact: Gianfranco Ferraccioli, MD,professor
    • Principal Investigator: Gianfranco Ferraccioli, MD,professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
The primary outcome is the reduction of skin thickness
Evaluated by the modified Rodnan skin score.

Secondary Outcome Measures

Outcome Measure
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).

Collaborators and Investigators

• Sponsor: Università Politecnica delle Marche
• Investigators: Principal Investigator: Armando Gabrielli, MD,professor, Università Politecnica delle Marche

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Study Completion: February 1, 2009

Study Registration Dates

• First Submitted: January 29, 2007
• First Submitted That Met QC Criteria: January 29, 2007
• First Posted (Estimate): January 30, 2007

Study Record Updates

• Last Update Posted (Estimate): January 30, 2007
• Last Update Submitted That Met QC Criteria: January 29, 2007
• Last Verified: January 1, 2007

More Information

Terms related to this study

• Keywords: Scleroderma, Diffuse; Scleroderma, Systemic
• Additional Relevant MeSH Terms: Skin Diseases; Connective Tissue Diseases; Scleroderma, Systemic; Scleroderma, Diffuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: FARM5X8AWM