Diffusion tensor imaging in the SPRINT-MS clinical trial: Advancing trial methodology.

Area of Science:

• Neuroimaging
• Radiology
• Neurology

Background:

• SPRINT-MS was a phase 2 trial investigating ibudilast for progressive multiple sclerosis (MS).
• Multimodal imaging, including diffusion tensor imaging (DTI), was used to assess brain tissue integrity in the trial.
• This study refines DTI analysis methods for enhanced application in clinical trials for MS.

Purpose of the Study:

• To reassess diffusion tensor imaging (DTI) data from the SPRINT-MS trial.
• To evaluate the utility of specific DTI metrics as outcome measures in progressive multiple sclerosis clinical trials.

Main Methods:

• Advanced postprocessing of DTI data included corrections for motion and distortions.
• White matter regions of interest, including the cingulum and cerebellar peduncles, were analyzed.
• Median radial diffusivity was the primary outcome, analyzed using linear mixed-effects models with Holm correction.

Main Results:

• Significant differences in the rate of change of radial diffusivity were observed between ibudilast and placebo groups in the cingulum and cerebellar peduncles.
• Radial diffusivity changes indicated tissue preservation in the treatment group and deterioration in the placebo group.
• The observed changes were statistically significant (p < 0.04).

Conclusions:

• Diffusion tensor imaging (DTI) metrics, specifically radial diffusivity in the cingulum and cerebellar peduncles, show potential as outcome measures.
• These DTI findings suggest a role in assessing treatment efficacy in neuroprotective clinical trials for progressive multiple sclerosis.