Improved functional outcome after chronic stroke with delayed anti-Nogo-A therapy: A clinically relevant intention-to-treat analysis Journal Article

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Authors: Podraza, K. M.; Mehta, Y.; Husak, V. A.; Lippmann, E.; O'Brien, T. E.; Kartje, G. L.; Tsai, S. Y.
Article Title: Improved functional outcome after chronic stroke with delayed anti-Nogo-A therapy: A clinically relevant intention-to-treat analysis
Abstract: Many preclinical treatment strategies for stroke have failed when tested in human trials. Although the reasons for these translation failures are multifactorial, one potential concern is the statistical analysis of the preclinical data. One way to rigorously evaluate new therapies is to use an intention-to-treat analysis in preclinical studies. Therefore, in this study, we set out to evaluate the treatment efficacy of a potential clinically relevant therapeutic agent for stroke, i.e., anti-Nogo-A immunotherapy, using an intention-to-treat analysis. Adult rats were trained on the skilled forelimb reaching task and subsequently underwent an ischemic stroke. Nine weeks later, the rats either received intracerebroventricular anti-Nogo-A antibody, control antibody, or no treatment. Skilled reaching performance was assessed by a non-linear model using both an intention-to-treat and per-protocol analysis. Following testing, dendritic complexity was evaluated in the contralesional and perilesional sensorimotor cortex. Both intention-to-treat and per-protocol analysis showed that anti-Nogo-A immunotherapy resulted in statistically significant improved recovery on the skilled forelimb reaching task, although treatment effect was less (though statistically significant) in the intention-to-treat group. Improved functional performance was not shown to be associated with dendritic changes. In conclusion, this study provides evidence for the importance of using intention-to-treat paradigms in testing preclinical therapeutic strategies.
Journal Title: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
ISSN: 1559-7016; 0271-678X
Publisher: Unknown  
Journal Place: United States
Date Published: 2017
Start Page: 271678X17730994
Language: eng
DOI/URL:

10.1177/0271678X17730994
Notes: LR: 20170927; JID: 8112566; OTO: NOTNLM; 2017/09/28 06:00 [entrez]; 2017/09/28 06:00 [pubmed]; 2017/09/28 06:00 [medline]; aheadofprint; SO: J Cereb Blood Flow Metab. 2017 Jan 1:271678X17730994. doi: 10.1177/0271678X17730994.