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

ABSTRACT

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 SOD1 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 5,544 people (116 families) including 516 subjects with ALS (169 from SOD1 positive families) as well as 1,056 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.