A double-blind placebo-controlled trial of antioxidant therapy in limited cutaneous systemic sclerosis.

OBJECTIVE To evaluate the effects of a combination of micronutrient antioxidants (selenium, beta-carotene, vitamin C, vitamin E and methionine) with allopurinol in patients with limited cutaneous systemic sclerosis (SSc). METHODS The study was designed as a placebo-controlled double-blind crossover study. A carryover effect was detected retrospectively for some of the prescribed antioxidants, and so the data were analysed as: (a) a between group comparison of the first 10 week treatment period; and (b) a within group comparison of the first and second 10-week periods in those who received placebo treatment first. Study end-points were plasma von Willebrand factor (vWF), thermographic response to a standard cold challenge, frequency and duration of Raynaud's attacks, patient opinion, and specialised biochemical parameters (fatty acid profiles, antioxidants and markers of free radical injury). RESULTS Thirty-three patients were recruited. The median duration of Raynaud's phenomenon was 10 years (range 2 to 50 years) in the active-first group and 10 years (range 4 to 53 years) in the placebo-first group. In the 10-week study, there were no differences between the active and placebo groups in the change from baseline for vWF, for the parameters of the rewarming curve, or for patients' symptoms. Despite a rise in circulating antioxidant levels, there was no fall in markers of free radical mediated injury. In the 20-week cross-over study, patients did not experience any clinical benefit from active treatment compared to placebo. CONCLUSION No clinical benefit could be demonstrated from active treatment. There are several possible explanations for this negative result, including the short duration of therapy. It is possible that antioxidant therapy, to be effective, needs to be given early in the SSc disease process, before the onset of irreversible tissue damage.