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 (sel enium, 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 defected retrospectively for some of the prescribe d antioxidants, and so the data were analysed as: (a) a between group compa rison of the first 10 week treatment period; and (b) a within group compari son of the first and second 10-week periods in those who received placebo t reatment first. Study end-points were plasma von Willebrand factor (vWF), t hermographic response to a standard cold challenge, frequency and duration of Raynaud's attacks, patient opinion, and specialised biochemical paramete rs (fatty acid profiles, antioxidants and markers of free radical injury). Results Thirty-three patients were recruited. The median duration of Raynaud's phen omenon 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. rn the 10-week stud y, there were no differences between the active and placebo groups in the c hange from baseline for vWF for the parameters of the rewarming curve, or f or patients' symptoms. Despite a rise in circulating antioxidant levels, th ere 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 act ive 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 effect ive, needs to be given early in the SSc disease process, before the onset o f irreversible tissue damage.