Abstract
Spinocerebellar ataxias (SCAs) are rare autosomal dominant inherited neurological disorders characterized by progressive cerebellar symptoms. In the past decades, several pharmacological and non-pharmacological symptomatic treatments were tested in clinical trials for their efficacy towards ataxia, but no long-lasting effective therapies have been yet established.
In this chapter we briefly reviewed the literature on both pharmacological trials and rehabilitating treatments performed in SCAs, with the aim of gathering information on trial objectives and methodology and discuss fundamental elements to consider in future trials.
For the design of meaningful clinical trials, the research question and associated hypotheses need to be well understood in terms of characteristics of the disease, intervention under study, target population, and measurement instruments. Randomized placebo-controlled designs are considered the primary research methodology for control of biases and confounding variables. New adaptive trial designs are also providing interesting options in order to reduce the number of subjects and speed up therapeutic deployment in rare diseases. In fact, the most challenging factors in clinical trials for SCA diseases are to maximize trial power with the minimum number of subjects, and to rely on the most sensitive outcome measures. Large collaborative initiatives on natural history studies for SCAs will provide the perfect support to ensure recruitment of a correctly powered number of patients, the number of appropriate sample sizes with targeted selection of stratified patient groups, and the knowledge about responsiveness to changes of the currently available outcome measures.
At present, the most important gap to be filled with respect to trial readiness in SCAs is the definition of outcome measures that will efficiently capture disease-related functional and structural changes occurring during disease course or in response to therapeutical interventions. The rarity and additional clinical diversity of conditions may require differential outcome sets for different purposes and different phases of the diseases (e.g., pre-clinical phase, and symptomatic stages). The other necessary and complementary element to advance in cure of SCAs will be availability of innovative and efficacious therapeutic options allowing real improvements in patient’s life.
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Mariotti, C., Fichera, M., Nanetti, L. (2023). How to Design a Therapeutic Trial in SCAs. In: Soong, Bw., Manto, M., Brice, A., Pulst, S.M. (eds) Trials for Cerebellar Ataxias. Contemporary Clinical Neuroscience. Springer, Cham. https://doi.org/10.1007/978-3-031-24345-5_8
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