A double-blind, placebo-controlled randomized clinical trial of alpha-tocopherol (vitamin E) in the treatment of amyotrophic lateral sclerosis

INTRODUCTION: Increasing evidence suggests that oxidative stress may be inv olved in the pathogenesis of amyotrophic lateral sclerosis (ALS). The antio xidant vitamin E (alpha -tocopherol) has been shown to slow down the onset and progression of paralysis in transgenic mice expressing a mutation in su peroxide dismutase found in certain forms of familial ALS, The current stud y was designed to determine whether a-tocopherol (500 mg b.i.d.) may be eff icacious in the treatment of ALS. METHODS: Two hundred and eighty-nine patients with ALS of less than 5 years duration, treated with riluzole, were enrolled in this study, and were ran domly assigned to receive either alpha -tocopherol or placebo daily for one year. The primary outcome measure was the rate of deterioration of functio n assessed by the modified Norris limb scale, Patients were assessed at ent ry, and every 3 months thereafter during the study period. Survival was als o recorded. Biochemical markers of oxidative stress were measured in a subs et of patients on entry and after 3 months of treatment. RESULTS: After 12 months of treatment, alpha -tocopherol had no effect on t he primary outcome measure. Survival was not influenced by treatment. Among secondary outcome measures, patients given alpha -tocopherol were less lik ely to progress from the milder state A to the more severe state B (P=0.046 ) of the: ALS Health State scale. After 3 months treatment, analysis of oxi dative stress markers showed an increase in glutathione peroxidase activity in plasma (P=0.0389) and a decrease in plasma levels of thiobarbituric aci d reactive species (P=0,0055)in the group of patients given alpha -tocopher ol in combination with riluzole. CONCLUSION: Although alpha -tocopherol did not appear to affect the sur/iva l and motor function in ALS, patients receiving riluzole plus alpha -tocoph erol remained longer in the milder states of the ALS Health State scale and showed, after 3 months, changes in biochemical markers of oxidative stress . Further studies are required to confirm the greater sensitivity of the AL S Health State scale over other clinical endpoints.