This Phase 2 clinical trial investigates the use of repetitive transcranial magnetic stimulation (rTMS) as a potential treatment for motor and cognitive symptoms in Progressive Supranuclear Palsy[1]. The trial represents an innovative non-pharmacological approach to addressing the significant unmet medical needs in PSP, a rapidly progressive atypical parkinsonian disorder with limited treatment options.
Progressive supranuclear palsy (PSP) is a 4R-tauopathy characterized by vertical supranuclear gaze palsy, postural instability with falls, parkinsonism, and frontal cognitive dysfunction[2]. Current pharmacological treatments provide minimal benefit, making non-invasive brain stimulation an attractive therapeutic avenue.
| Parameter | Value |
|---|---|
| NCT Number | NCT04468932 |
| Status | Recruiting |
| Study Type | Interventional (Phase 2) |
| Intervention | Repetitive Transcranial Magnetic Stimulation (rTMS) |
| Conditions | Progressive Supranuclear Palsy (PSP) |
| Design | Randomized, Sham-controlled |
| Allocation | Parallel |
| Blinding | Double-blind |
PSP involves progressive degeneration of subcortical and cortical structures[3]:
| Brain Region | Pathology | Clinical Correlate |
|---|---|---|
| Substantia nigra | Tau-positive NFTs | Parkinsonism |
| Globus pallidus | Neuronal loss | Rigidity, bradykinesia |
| Superior colliculus | Tau pathology | Gaze palsy |
| Frontal cortex | Neuronal loss | Cognitive dysfunction |
| Brainstem | Tau pathology | Dysphagia, sleep issues |
The frontal cortex plays a critical role in PSP pathophysiology[4]:
Executive Dysfunction
Behavioral Changes
Motor Planning
Repetitive transcranial magnetic stimulation uses electromagnetic induction to modulate cortical excitability[5]. Key mechanisms include:
Multiple studies have evaluated rTMS in Parkinson's disease and related disorders[6]:
Safety and Tolerability
Motor Function
Cognitive Function
Behavioral Measures
Quality of Life
| Timepoint | Assessments |
|---|---|
| Baseline | Full clinical assessment |
| Mid-treatment | Safety, preliminary efficacy |
| Post-treatment | Primary endpoints |
| Follow-up | Durability assessment (1-3 months) |
rTMS may benefit PSP through several mechanisms:
| PSP Symptom | rTMS Target | Expected Benefit |
|---|---|---|
| Bradykinesia | M1 | Improved movement initiation |
| Rigidity | M1 | Reduced muscle tone |
| Gaze palsy | Frontal eye fields | Limited direct benefit |
| Falls | DLPFC/motor | Postural control |
| Cognitive decline | DLPFC | Executive function |
| Apathy | DLPFC | Mood and motivation |
TMS Contraindications
Medical Contraindications
rTMS is generally well-tolerated[7:1]:
PSP has limited treatment options[11]:
| Trial | Intervention | Phase | Status | Outcome |
|---|---|---|---|---|
| NCT04468932 | rTMS | Phase 2 | Recruiting | Motor, cognitive |
| NCT05318985 | Bepranemab | Phase 2 | Active | Tau reduction |
| NCT04564555 | CoQ10 | Phase 3 | Completed | Minimal benefit |
| NCT05297202 | Lithium | Phase 2 | Completed | Negative |
rTMS may be combined with:
Future trials may incorporate:
Progressive supranuclear palsy: current management and future treatments. Lancet Neurology. 2019. ↩︎
Current concepts in the treatment of progressive supranuclear palsy. Movement Disorders. 2018. ↩︎
Neuroimaging in progressive supranuclear palsy. Journal of Neurology. 2015. ↩︎
Frontal cognitive dysfunction in atypical parkinsonism. Journal of Neural Transmission. 2020. ↩︎
Repetitive transcranial magnetic stimulation in neurodegenerative diseases. Clinical Neurophysiology. 2019. ↩︎
Transcranial magnetic stimulation in Parkinson's disease and atypical parkinsonism. Parkinsonism & Related Disorders. 2019. ↩︎
Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation. Clinical Neurophysiology. 2014. ↩︎ ↩︎
Transcranial magnetic stimulation in corticobasal degeneration and progressive supranuclear palsy. Brain Stimulation. 2019. ↩︎
Repetitive transcranial magnetic stimulation for motor symptoms in Parkinson's disease. Neurology. 2020. ↩︎
Transcranial magnetic stimulation as a biomarker in Parkinson's disease. Parkinsonism & Related Disorders. 2022. ↩︎
Progressive supranuclear palsy: management and palliative care. Current Treatment Options in Neurology. 2014. ↩︎