Wijeratne, PA;
Johnson, EB;
Eshaghi, A;
Aksman, L;
Gregory, S;
Johnson, HJ;
Poudel, GR;
... Alexander, DC; + view all
(2020)
Robust markers and sample sizes for multi‐centre trials of Huntington's disease.
Annals of Neurology
, 87
(5)
pp. 751-762.
10.1002/ana.25709.
Preview |
Text
Aksman_Voana.25709.pdf - Published Version Download (8MB) | Preview |
Abstract
Objective: The identification of sensitive biomarkers is essential to validate therapeutics for Huntington disease (HD). We directly compare structural imaging markers across the largest collective imaging HD dataset to identify a set of imaging markers robust to multicenter variation and to derive upper estimates on sample sizes for clinical trials in HD. Methods: We used 1 postprocessing pipeline to retrospectively analyze T1-weighted magnetic resonance imaging (MRI) scans from 624 participants at 3 time points, from the PREDICT-HD, TRACK-HD, and IMAGE-HD studies. We used mixed effects models to adjust regional brain volumes for covariates, calculate effect sizes, and simulate possible treatment effects in disease-affected anatomical regions. We used our model to estimate the statistical power of possible treatment effects for anatomical regions and clinical markers. Results: We identified a set of common anatomical regions that have similarly large standardized effect sizes (>0.5) between healthy control and premanifest HD (PreHD) groups. These included subcortical, white matter, and cortical regions and nonventricular cerebrospinal fluid (CSF). We also observed a consistent spatial distribution of effect size by region across the whole brain. We found that multicenter studies were necessary to capture treatment effect variance; for a 20% treatment effect, power of >80% was achieved for the caudate (n = 661), pallidum (n = 687), and nonventricular CSF (n = 939), and, crucially, these imaging markers provided greater power than standard clinical markers. Interpretation: Our findings provide the first cross-study validation of structural imaging markers in HD, supporting the use of these measurements as endpoints for both observational studies and clinical trials
Archive Staff Only
 |
View Item |
