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MRI derived brain atrophy in PSP and MSA-P. Determining sample size to detect treatment effects
Dominic C Paviour1, Shona L Price, Andrew J Lees
1The Sara Koe PSP Research Centre, Institute of Neurology, 1 Wakefield Street, London WC1N, UK. dpaviour@dementia.ion.ucl.ac.uk
Abstract:
Progressive supranuclear palsy (PSP) and multiple system (MSA) atrophy are associated with progressive brain atrophy. Serial MRI can be applied in order to measure this change in brain volume and to calculate atrophy rates. We evaluated MRI derived whole brain and regional atrophy rates as potential markers of progression in PSP and the Parkinsonian variant of multiple system atrophy (MSA-P). 17 patients with PSP, 9 with MSA-P and 18 healthy controls underwent two MRI brain scans. MRI scans were registered, and brain and regional atrophy rates (midbrain, pons, cerebellum, third and lateral ventricles) measured. Sample sizes required to detect the effect of a proposed disease-modifying treatment were estimated. The effect of scan interval on the variance of the atrophy rates and sample size was assessed. Based on the calculated yearly rates of atrophy, for a drug effect equivalent to a 30% reduction in atrophy, fewer PSP subjects are required in each treatment arm when using midbrain rather than whole brain atrophy rates (183 cf. 499). Fewer MSA-P subjects are required, using pontine/cerebellar, rather than whole brain atrophy rates (164/129 cf. 794). A reduction in the variance of measured atrophy rates was observed with a longer scan interval. Regional rather than whole brain atrophy rates calculated from volumetric serial MRI brain scans in PSP and MSA-P provide a more practical and powerful means of monitoring disease progression in clinical trials.
Insights
Serial MRI reveals regional brain atrophy rates are better markers for tracking disease progression in progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). This improves clinical trial efficiency for these neurodegenerative conditions.
Area of Science:
- Neuroimaging
- Neurology
- Clinical Trials
Background:
- Progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) are characterized by progressive brain atrophy.
- Serial MRI is a valuable tool for quantifying brain volume changes and atrophy rates.
Purpose of the Study:
- To evaluate MRI-derived whole brain and regional atrophy rates as progression markers in PSP and the Parkinsonian variant of MSA (MSA-P).
- To estimate sample sizes for clinical trials investigating disease-modifying treatments for PSP and MSA-P.
Main Methods:
- 17 PSP patients, 9 MSA-P patients, and 18 healthy controls underwent two MRI brain scans.
- Brain and regional atrophy rates (midbrain, pons, cerebellum, ventricles) were measured using registered MRI scans.
- The impact of scan interval on atrophy rate variance and sample size was analyzed.
Main Results:
- Regional atrophy rates, specifically in the midbrain for PSP and pons/cerebellum for MSA-P, require fewer subjects for detecting treatment effects compared to whole brain atrophy rates.
- A longer scan interval reduced the variance of measured atrophy rates, enhancing statistical power.
- Regional atrophy metrics offer a more practical and powerful approach for monitoring disease progression in clinical trials.
Conclusions:
- Volumetric serial MRI, particularly using regional atrophy rates, is a more efficient method for monitoring disease progression in PSP and MSA-P.
- This approach can optimize the design and reduce the sample size requirements for clinical trials targeting these neurodegenerative diseases.
