TY - JOUR
T1 - Rates of brain atrophy and clinical decline over 6 and 12-month intervals in PSP
T2 - Determining sample size for treatment trials
AU - Whitwell, Jennifer L.
AU - Xu, Jia
AU - Mandrekar, Jay N.
AU - Gunter, Jeffrey L.
AU - Jack, Clifford R.
AU - Josephs, Keith A.
N1 - Funding Information:
This work was supported by the Dana Foundation; National Institutes of Health (grant numbers R01-DC010367 , R01-AG037491 , R21-AG38736 , and R01-AG11378 ) and the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Foundation . We would like to acknowledge Drs. Scott Eggers, J. Eric Ahlskog and Joseph Matsumoto for referring patients for this study.
PY - 2012/3
Y1 - 2012/3
N2 - Imaging biomarkers are useful outcome measures in treatment trials. We compared sample size estimates for future treatment trials performed over 6 or 12-months in progressive supranuclear palsy using both imaging and clinical measures. We recruited 16 probable progressive supranuclear palsy patients that underwent baseline, 6 and 12-month brain scans, and 16 age-matched controls with serial scans. Disease severity was measured at each time-point using the progressive supranuclear palsy rating scale. Rates of ventricular expansion and rates of atrophy of the whole brain, superior frontal lobe, thalamus, caudate and midbrain were calculated. Rates of atrophy and clinical decline were used to calculate sample sizes required to power placebo-controlled treatment trials over 6 and 12-months. Rates of whole brain, thalamus and midbrain atrophy, and ventricular expansion, were increased over 6 and 12-months in progressive supranuclear palsy compared to controls. The progressive supranuclear palsy rating scale increased by 9 points over 6-months, and 18 points over 12-months. The smallest sample size estimates for treatment trials over 6-months were achieved using rate of midbrain atrophy, followed by rate of whole brain atrophy and ventricular expansion. Sample size estimates were further reduced over 12-month intervals. Sample size estimates for the progressive supranuclear palsy rating scale were worse than imaging measures over 6-months, but comparable over 12-months. Atrophy and clinical decline can be detected over 6-months in progressive supranuclear palsy. Sample size estimates suggest that treatment trials could be performed over this interval, with rate of midbrain atrophy providing the best outcome measure.
AB - Imaging biomarkers are useful outcome measures in treatment trials. We compared sample size estimates for future treatment trials performed over 6 or 12-months in progressive supranuclear palsy using both imaging and clinical measures. We recruited 16 probable progressive supranuclear palsy patients that underwent baseline, 6 and 12-month brain scans, and 16 age-matched controls with serial scans. Disease severity was measured at each time-point using the progressive supranuclear palsy rating scale. Rates of ventricular expansion and rates of atrophy of the whole brain, superior frontal lobe, thalamus, caudate and midbrain were calculated. Rates of atrophy and clinical decline were used to calculate sample sizes required to power placebo-controlled treatment trials over 6 and 12-months. Rates of whole brain, thalamus and midbrain atrophy, and ventricular expansion, were increased over 6 and 12-months in progressive supranuclear palsy compared to controls. The progressive supranuclear palsy rating scale increased by 9 points over 6-months, and 18 points over 12-months. The smallest sample size estimates for treatment trials over 6-months were achieved using rate of midbrain atrophy, followed by rate of whole brain atrophy and ventricular expansion. Sample size estimates were further reduced over 12-month intervals. Sample size estimates for the progressive supranuclear palsy rating scale were worse than imaging measures over 6-months, but comparable over 12-months. Atrophy and clinical decline can be detected over 6-months in progressive supranuclear palsy. Sample size estimates suggest that treatment trials could be performed over this interval, with rate of midbrain atrophy providing the best outcome measure.
KW - Atrophy
KW - Midbrain
KW - Power calculations
KW - Progressive supranuclear palsy
KW - Short interval
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U2 - 10.1016/j.parkreldis.2011.10.013
DO - 10.1016/j.parkreldis.2011.10.013
M3 - Article
C2 - 22079523
AN - SCOPUS:84857441699
SN - 1353-8020
VL - 18
SP - 252
EP - 256
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
IS - 3
ER -