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Mov Disord. 2017 Jun;32(6):842-852. doi: 10.1002/mds.26973. Epub 2017 Apr 24.

Longitudinal magnetic resonance imaging in progressive supranuclear palsy: A new combined score for clinical trials.

Author information

1
Department of Neurology, Technische Universität München, Munich, Germany.
2
German Center for Neurodegenerative Diseases, Munich, Germany.
3
Department of Neurology, University Hospital Gießen and Marburg, Marburg, Germany.
4
Institute for Medical Biometry, Epidemiology and Medical Informatics, Saarland University, Campus Homburg, Germany.
5
Second Department of Neurology, Attikon University Hospital, University of Athens, Athens, Greece.
6
Department of Neurology, University of Ulm, Ulm, Germany.
7
Medical Department, Noscira SA, Madrid, Spain.
8
Memory and Aging Center, Department of Neurology, University of California, San Francisco, California, USA.
9
Swiss Epilepsy Centre, Klinik Lengg, Zurich, Switzerland.

Abstract

BACKGROUND:

Two recent, randomized, placebo-controlled phase II/III trials (clinicaltrials.gov: NCT01110720, NCT01049399) of davunetide and tideglusib in progressive supranuclear palsy (PSP) generated prospective, 1-year longitudinal datasets of high-resolution T1-weighted three-dimensional MRI.

OBJECTIVE:

The objective of this study was to develop a quantitative MRI disease progression measurement for clinical trials.

METHODS:

The authors performed a fully automated quantitative MRI analysis employing atlas-based volumetry and provide sample size calculations based on data collected in 99 PSP patients assigned to placebo in these trials. Based on individual volumes of 44 brain compartments and structures at baseline and 52 weeks of follow-up, means and standard deviations of annualized percentage volume changes were used to estimate standardized effect sizes and the required sample sizes per group for future 2-armed, placebo-controlled therapeutic trials.

RESULTS:

The highest standardized effect sizes were found for midbrain, frontal lobes, and the third ventricle. Using the annualized percentage volume change of these structures to detect a 50% change in the 1-year progression (80% power, significance level 5%) required lower numbers of patients per group (third ventricle, n = 32; midbrain, n = 37; frontal lobe, n = 43) than the best clinical scale (PSP rating scale total score, n = 58). A combination of volume changes in these 3 structures reduced the number of required patients to only 20 and correlated best with the progression in the clinical scales.

CONCLUSIONS:

We propose the 1-year change in the volumes of third ventricle, midbrain, and frontal lobe as combined imaging read-out for clinical trials in PSP that require the least number of patients for detecting efficacy to reduce brain atrophy. © 2017 International Parkinson and Movement Disorder Society.

KEYWORDS:

clinical trials; magnetic resonance imaging; power calculation; progressive supranuclear palsy; volumetry

PMID:
28436538
PMCID:
PMC5808453
DOI:
10.1002/mds.26973
[Indexed for MEDLINE]
Free PMC Article

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