Müller, H-P;
Huppertz, H-J;
Dreyhaupt, J;
Ludolph, AC;
Tabrizi, SJ;
Roos, RAC;
Durr, A;
... Kassubek, J; + view all
(2019)
Combined cerebral atrophy score in Huntington's disease based on atlas-based MRI volumetry: Sample size calculations for clinical trials.
Parkinsonism & Related Disorders
, 63
pp. 179-184.
10.1016/j.parkreldis.2019.02.004.
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Abstract
INTRODUCTION: A volumetric MRI analysis of longitudinal regional cerebral atrophy in Huntington's disease (HD) was performed as a read-out of disease progression to calculate sample sizes for future clinical trials. METHODS: This study was based on MRI data of 59 patients with HD and 40 controls recruited within the framework of the PADDINGTON study and investigated at baseline and follow-up after 6 and 15 months. Automatic atlas-based volumetry (ABV) of structural T1-weighted scans was used to calculate longitudinal volume changes of brain structures relevant in HD and to assess standardized effect sizes and sample sizes required for potential future studies. RESULTS: Atrophy rates were largest in the caudate (-3.4%), putamen (-2.8%), nucleus accumbens (-1.6%), and the parietal lobes (-1.7%); the lateral ventricles showed an expansion by 6.0%. Corresponding effect sizes were -1.35 (caudate), -0.84 (putamen), -0.91 (nucleus accumbens), -1.05 (parietal lobe), and 0.92 (lateral ventricles) leading to N = 36 subjects per study group for detecting a 50% attenuation of atrophy for the best performing structure (caudate). A combined score of volume changes in non-overlapping compartments (striatum, parietal lobes, lateral ventricles) increased the effect size to -1.60 and substantially reduced the required sample sizes by 10 to N = 26 subjects per study group. This combined imaging score correlated significantly both with the CAP score and with the progression of the clinical phenotype. CONCLUSION: We propose ABV of the striatum together with parietal lobe and lateral ventricle volumes as a combined imaging read-out for progression studies including clinical trials in HD.
| Type: | Article |
|---|---|
| Title: | Combined cerebral atrophy score in Huntington's disease based on atlas-based MRI volumetry: Sample size calculations for clinical trials |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.parkreldis.2019.02.004 |
| Publisher version: | https://doi.org/10.1016/j.parkreldis.2019.02.004 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Atlas-based volumetry, Clinical trial, Effect size, Huntington's disease, Longitudinal study, Multicenter study, Surrogate marker |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10072123 |
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