To Reduce Trial Size Use Muscle, ALS Scientists Say

Cutting Trials Down to Size? A growing panel of biomarkers may help facilitate the testing of potential ALS therapies in the clinic by reducing sample size (see January 2017 conference news). [Image: IBBI under CC BY-NC-ND 2.0 license.]

A simple blood test may help scientists detect potential treatment effects in fewer people with the disease according to a retrospective analysis led by University Medical Center Utrecht’s Leonard van den Berg in the Netherlands.

The surrogate outcome measure, originally proposed by physicians at the Hôpital de la Pitié-Salpêtrière in 2005 in Paris, France, determines the levels of creatinine, a biomarker that reflects total muscle mass (Paillisse et al., 2005). The approach builds on previous studies, which suggest that the levels of creatinine in the blood may help forecast the prognosis of people with ALS (Chio et al., 2014; Atassi et al., 2014).

The study is published online on October 30 in the Journal of Neurology, Neurosurgery and Psychiatry.

Changes in creatinine levels correlated with key functional outcomes over time including ALS-FRS-R, muscle strength and survival (p<0.001). A total of 1,241 people with ALS participated in the study.

The approach, according to a subsequent power analysis, may reduce the number of clinical trial participants needed to evaluate efficacy of potential ALS therapies after 18 months by more than 20%. What’s more, the implementation of this test may also help facilitate analysis of the results by reducing variability in clinical trials with more than a 10-month follow-up. The test is one of a growing number of approaches that may facilitate the evaluation of therapies for ALS by increasing the ability to detect potential treatment effects (see May 2017 conference news).

Featured Paper

van Eijk RPA, Eijkemans MJC, Ferguson TA, Nikolakopoulos S, Veldink JH, van den Berg LH. Monitoring disease progression with plasma creatinine in amyotrophic lateral sclerosis clinical trials. J Neurol Neurosurg Psychiatry. 2017 Oct 30. [PubMed].


Chiò A, Calvo A, Bovio G, Canosa A, Bertuzzo D, Galmozzi F, Cugnasco P, Clerico M, De Mercanti S, Bersano E, Cammarosano S, Ilardi A, Manera U, Moglia C, Sideri R, Marinou K, Bottacchi E, Pisano F, Cantello R, Mazzini L, Mora G; Piemonte and Valle d’Aosta Register for Amyotrophic Lateral Sclerosis. Amyotrophic lateral sclerosis outcome measures and the role of albumin and creatinine: a population-based study. JAMA Neurol. 2014 Sep;71(9):1134-42. [PubMed].

Atassi N, Berry J, Shui A, Zach N, Sherman A, Sinani E, Walker J, Katsovskiy I, Schoenfeld D, Cudkowicz M, Leitner M. The PRO-ACT database: design, initial analyses, and predictive features. Neurology. 2014 Nov 4;83(19):1719-25. [PubMed].

Paillisse C, Lacomblez L, Dib M, Bensimon G, Garcia-Acosta S, Meininger V. Prognostic factors for survival in amyotrophic lateral sclerosis patients treated with riluzole. Amyotroph Lateral Scler Other Motor Neuron Disord. 2005 Mar;6(1):37-44. [PubMed].


ALS-FRS-R clinical trial clinical trial design creatinine disease-als power analysis sample size topic-biomarkers topic-clinical topic-randd
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