N-of-1 Clinical Trial Design for CBS/PSP

SUMMARY

# N-of-1 Clinical Trial Design for CBS/PSP ## Background and Rationale N-of-1 trials represent a personalized medicine approach using rigorous single-patient crossover designs to optimize treatment for individual patients. This methodology addresses the critical challenge of conducting meaningful clinical research in rare neurodegenerative diseases like corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP), where traditional randomized controlled trials are impractical due to limi

METHODOLOGY NOTES

Phase 1: Patient screening and baseline assessment (Weeks 1-4). Recruit 20 CBS/PSP patients meeting established diagnostic criteria. Conduct comprehensive evaluations including UPDRS-III, PSP Rating Scale, cognitive batteries, lumbar puncture for CSF biomarkers, and brain MRI. Establish individual baseline variability through repeated measures. Phase 2: Randomization and first treatment period (Weeks 5-8). Randomize each patient to either experimental intervention or control condition using computer-generated sequences. Administer treatments daily with weekly clinical assessments and continuous digital monitoring via ActiGraph accelerometers. Phase 3: First washout period (Weeks 9-10). Discontinue active treatments while maintaining safety monitoring and outcome measurements. Phase 4: Crossover treatment period (Weeks 11-14). Switch patients to alternative treatment arm with identical monitoring protocols. Phase 5: Second washout and optional repeat cycle (Weeks 15-18). Additional wash