Given that CBD is a rare disease, minimizing the number of participants in clinical trials is critical. A primary aim of this work was to identify the brain regions that require the lowest sample sizes to detect potential therapeutic effects for CBD clinical trials.
By using both the exploratory voxelwise analysis and regional volumetric measurements of brain atrophy, we have shown:
- The brain regions-of-interest that require the lowest sample sizes to detect potential therapeutic effects for CBD clinical trials.
- Cortical regional volumes and diffusion measures illustrate the rapid progression of CBD with statistically significant changes in structure as early as 6 months from baseline visit.
- Assessment of the regional volume and diffusion changes over time using a neuroimaging processing/analysis pipeline purpose-built for clinical trials can generate smaller sample size requirements compared with other tools.
This work provides a detailed analysis of MRI data from the 4RTNI study. Our results show that progressive, regional brain atrophy can be effectively assessed using quantitative analysis of MR images with reasonable sample sizes over a relatively short timeframe. As such, these imaging biomarkers appear to be promising for assessment of the efficacy of disease-modifying therapeutics in CBD clinical trials.