The MOTIVE-PSP Initiative (NCT04691635) is a multi-center, longitudinal observational study designed to identify reliable biomarkers for progressive supranuclear palsy (PSP) diagnosis, phenotypization, and progression monitoring over a 1-year follow-up period.
This initiative represents a critical effort to address the pressing need for objective biomarkers in PSP clinical research, which has historically relied on subjective clinical assessments that may miss subtle disease progression.
| Parameter |
Value |
| NCT ID |
NCT04691635 |
| Status |
Completed |
| Phase |
Observational |
| Study Design |
Multi-center, prospective longitudinal |
| Duration |
1 year |
| Cohort Size |
~200 PSP patients |
| Sponsor |
Multiple academic centers |
| Collaborators |
CurePSP, PSP Association |
-
Motor Assessment Biomarkers
- Evaluate standardized clinical motor scales as diagnostic biomarkers
- Assess sensitivity to progression over 1 year
- Compare quantitative vs. qualitative measures
-
Cognitive Function Assessment
- Characterize cognitive phenotype changes over time
- Identify cognitive biomarkers for disease staging
-
Language and Speech Biomarkers
- Assess speech and language function using standardized batteries
- Evaluate potential for early detection
-
Cerebrospinal Fluid Biomarkers
- Measure tau species (total tau, phosphorylated tau)
- Identify novel CSF markers of disease progression
- Correlate with clinical measures
-
Neuroimaging Progression Markers
- MRI-based volumetric analysis
- Diffusion tensor imaging changes
- Tau PET signal correlation
| Timepoint |
Assessments |
| Baseline |
Full motor, cognitive, CSF, MRI battery |
| 3 months |
Motor scales, cognitive tests |
| 6 months |
Full battery |
| 9 months |
Motor scales, cognitive tests |
| 12 months |
Full battery (primary endpoint) |
- Diagnosis: Probable PSP (Richardson syndrome or PSP variants)
- Age: 40-85 years
- Disease Duration: Any
- Exclusion: Significant comorbidities affecting assessments
-
Motor Function Assessment
- PSP Rating Scale (PSPRS)
- Unified Parkinson's Disease Rating Scale (UPDRS) Part III
- Timed Up and Go test
- 10-meter walk test
-
Cognitive Evaluation
- Montreal Cognitive Assessment (MoCA)
- Trail Making Test A and B
- Digit Span tests
-
Language Assessment
- Western Aphasia Battery components
- Speech acoustic analysis
-
CSF Biomarker Panel
-
Neuroimaging Markers
- Brain volume changes
- Midbrain atrophy assessment
- White matter integrity
PSP progression is often measured through clinic visits every 6-12 months, but:
- Symptom fluctuations occur daily
- Subtle changes may be missed between visits
- Subjective measures can vary between assessors
- Lack of objective biomarkers hinders clinical trial design
Reliable biomarkers are needed for:
- Early Diagnosis: Earlier identification of PSP vs. PD
- Disease Staging: Objective classification of disease severity
- Clinical Trials: Surrogate endpoints for therapeutic studies
- Patient Stratification: Phenotype-specific subgroups
- Progression Tracking: Sensitive measures of decline
The initiative leverages modern digital health technologies:
- Wearable sensors for continuous monitoring
- Smartphone applications for daily tracking
- Remote assessment capabilities
¶ Results and Implications
The MOTIVE-PSP Initiative has contributed to understanding:
- Motor Biomarkers: Quantitative measures show promise for tracking progression
- Cognitive Phenotypes: Distinct patterns identified across PSP subtypes
- CSF Markers: NfL shows correlation with disease severity
- Imaging: Midbrain atrophy remains key diagnostic marker
The initiative provides:
- Validated biomarker panels for future therapeutic studies
- Standardized assessment protocols
- Baseline data for natural history studies
- Foundation for precision medicine in PSP
The MOTIVE-PSP Initiative contributes to personalized treatment approaches in several ways:
- Biomarker-Driven Diagnosis: Objective measures can confirm clinical diagnosis
- Progression Monitoring: Track individual patient trajectory more accurately
- Treatment Response: Objective endpoints for evaluating therapy effectiveness
- Prognostic Counseling: Better predictions of disease course
Implementing biomarker-based approaches in PSP care could:
- Reduce diagnostic delays through earlierobjective testing
- Enable proactive care planning as disease progresses
- Improve resource allocation based on disease stage
- Facilitate telehealth monitoring between in-person visits
The collaborative nature of this initiative establishes:
- Standardized protocols for multi-site studies
- Shared data repositories for aggregate analysis
- Training programs for consistent assessment
- Infrastructure for future therapeutic trials
A related study (NCT07389018) is evaluating the feasibility of Syde® digital endpoints for monitoring patients with PSP-Richardson syndrome. This study:
- Uses wearable sensors to capture movement data
- Employs machine learning algorithms for analysis
- Aims to develop objective digital biomarkers
- Completes in January 2028