Preventing familial amyotrophic lateral sclerosis: Is a clinical trial feasible?

Objective: To evaluate the feasibility of a clinical trial designed to delay or prevent the onset of disease amongst subjects at risk for familial amyotrophic lateral sclerosis (fALS). Background: The success of many agents in prolonging survival in the SOD 1 model of ALS has not been translated into effective therapies for patients with ALS. It is our hypothesis that a trial in fALS may reproduce the positive effects seen in fALS animals. Methods: Pedigrees with at least two affected family members were constructed. Unaffected family members were assigned a risk status based on their relationship to affected subjects. Attitudes towards genetic testing were ascertained amongst the at-risk family members. Results: We obtained data about 5544 people (116 families) including 516 subjects with ALS (169 from SOD I positive families) as well as 1056 subjects "definitely" or "probably" at risk for fALS (335 from SOD1 positive families). In excess of 80% of subjects indicated an interest in participating in a future clinical trial directed at delaying the onset of the disease. Assuming the use of a therapeutic agent that will prolong the time to the onset of fALS by 50%, we estimate that a sample size of between 261 and 610 subjects 'definitely at risk' will be required (power 0.8) depending on whether patients are followed for 10 or 5 years respectively. Conclusions: A clinical trial in fALS may be feasible although such a trial would likely require prolonged follow-up and would require a therapeutic agent with a large clinical effect in order to be adequately powered. (c) 2006 Elsevier B.V. All rights reserved.