Effects of aminaftone 75 mg TID on soluble adhesion molecules: a 12-week, randomized, open-label pilot study in patients with systemic sclerosis.
BACKGROUND
Vasculopathy is one of the hallmarks of systemic sclerosis (SSc), characterized by endothelial activation and over expression of adhesion molecules. A preliminary in vitro study has suggested that aminaftone, a naphtohydrochinone used in the treatment of capillary disorders, may downregulate the expression of adhesion molecules in endothelial cells.


OBJECTIVE
This study investigated the ex vivo effects of aminaftone on soluble adhesion molecule concentrations in patients with SSc.


METHODS
This randomized, open-label pilot study was conducted in patients with SSc. Patients received baseline treatment for Raynaud's phenomenon (eg, calcium channel blockers and IV cyclic iloprost) with (test) or without (control) aminaftone 75 mg or placebo TID for 12 weeks. Standard treatment for Raynaud's phenomenon was allowed as long as the dose was stable for >or=3 months prior to randomization. Concentrations of soluble E-selectin adhesion molecule 1 (sELAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), and soluble intracellular adhesion molecule 1 (sICAM-1) were measured at baseline and 12 weeks, and their variation was tested using the analysis of variance for repeated measures with statistical correction. Laboratory analyses were performed by experienced personnel blinded to treatment assignment.


RESULTS
A total of 24 patients were enrolled (21 women, 3 men; mean age, 53.4 years; aminaftone, 12 patients; control, 12 patients). Decreases in mean (SD) sELAM-1 and sVCAM-1 concentrations were significantly greater in treated patients (sELAM-1, from 17.0 [7.8] to 11.9 [9.0] pg/mL; sVCAM-1, from 51.2 [12.9] to 40.8 [13.8] ng/mL) compared with controls (sELAM-1, from 20.3 [9.9] to 20.4 [10.5] pg/mL; sVCAM-1, from 56.8 [49.6] to 62.7 [40.6] ng/mL) (both, P < 0.05 [analysis of variance or repeated measures after Bonferroni correction]). No significant changes in sICAM-1 concentrations versus controls were observed.


CONCLUSIONS
In this small pilot study in this select group of patients with SSc, aminaftone was associated with downregulation of sELAM-1 and sVCAM-1 concentrations. Studies evaluating the potential role of aminaftone in the treatment of vascular sclerodermal disease and SSc are warranted.
Referral Center for Systemic Autoimmune Diseases, University of Milan, Milan, Italy. raffaella.scorza@unimi.it
Raffaella
R
Scorza
Alessandro
A
Santaniello
Giulia
G
Salazar
Stefania
S
Lenna
Silvia
S
Della Bella
Rita
R
Antonioli
Karen
K
Toussoun
Lorenzo
L
Beretta
D010129:4-Aminobenzoic Acid / Q000008:administration & dosage / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D019040:E-Selectin / Q000096:biosynthesis; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012595:Scleroderma, Systemic / Q000378:metabolism*; D012995:Solubility; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis; D062366:para-Aminobenzoates
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D062366:para-Aminobenzoates; C016217:aminaftone; D018799:Intercellular Adhesion Molecule-1; D010129:4-Aminobenzoic Acid