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Open Access 01-10-2010 | Diagnostic Neuroradiology

Cerebral atrophy as outcome measure in short-term phase 2 clinical trials in multiple sclerosis

Authors: I. J. van den Elskamp, B. Boden, V. Dattola, D. L. Knol, M. Filippi, L. Kappos, F. Fazekas, K. Wagner, C. Pohl, R. Sandbrink, C. H. Polman, B. M. J. Uitdehaag, F. Barkhof

Published in: Neuroradiology | Issue 10/2010

Abstract

Introduction

Cerebral atrophy is a compound measure of the neurodegenerative component of multiple sclerosis (MS) and a conceivable outcome measure for clinical trials monitoring the effect of neuroprotective agents. In this study, we evaluate the rate of cerebral atrophy in a 6-month period, investigate the predictive and explanatory value of other magnetic resonance imaging (MRI) measures in relation to cerebral atrophy, and determine sample sizes for future short-term clinical trials using cerebral atrophy as primary outcome measure.

Methods

One hundred thirty-five relapsing–remitting multiple sclerosis patients underwent six monthly MRI scans from which the percentage brain volume change (PBVC) and the number and volume of gadolinium (Gd)-enhancing lesions, T2 lesions, and persistent black holes (PBH) were determined. By means of multiple linear regression analysis, the relationship between focal MRI variables and PBVC was assessed. Sample size calculations were performed for all patients and subgroups selected for enhancement or a high T2 lesion load at baseline.

Results

A significant atrophy occurred over 6 months (PBVC = −0.33%, SE = 0.061, p < 0.0001). The number of baseline T2 lesions (p = 0.024), the on-study Gd-enhancing lesion volume (p = 0.044), and the number of on-study PBHs (p = 0.003) were associated with an increased rate of atrophy. For a 50% decrease in rate of atrophy, the sample size calculations showed that approximately 283 patients per arm are required in an unselected sampled population and 185 patients per arm are required in a selected population.

Conclusion

Within a 6-month period, significant atrophy can be detected and on-study associations of PBVC and PBHs emphasizes axonal loss to be a driving mechanism. Application as primary outcome measure in short-term clinical trials with feasible sample size requires a potent drug to obtain sufficient power.

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Title: Cerebral atrophy as outcome measure in short-term phase 2 clinical trials in multiple sclerosis
Authors: I. J. van den Elskamp
B. Boden
V. Dattola
D. L. Knol
M. Filippi
L. Kappos
F. Fazekas
K. Wagner
C. Pohl
R. Sandbrink
C. H. Polman
B. M. J. Uitdehaag
F. Barkhof
Publication date: 01-10-2010
Publisher: Springer-Verlag
Published in: Neuroradiology / Issue 10/2010
Print ISSN: 0028-3940
Electronic ISSN: 1432-1920
DOI: https://doi.org/10.1007/s00234-009-0645-1

ACC 2024 Congress

Springer Medicine

Cerebral atrophy as outcome measure in short-term phase 2 clinical trials in multiple sclerosis

Abstract

Introduction

Methods

Results

Conclusion

ACC 2024 Congress

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusion

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