tDCS as Treatment for Motor Function in PSP (NCT07291687)

Overview

This study evaluates transcranial direct current stimulation (tDCS) as a potential treatment for motor dysfunction in Progressive Supranuclear Palsy (PSP). PSP is a progressive neurodegenerative disorder characterized by vertical supranuclear gaze palsy, axial rigidity, postural instability, and bradykinesia. Despite extensive research, no disease-modifying treatments exist, making symptomatic management a critical area of investigation.

tDCS is a non-invasive brain stimulation technique that modulates cortical excitability through weak direct electrical currents delivered via electrodes placed on the scalp. The technique has shown promise in various neurological conditions including Parkinson's disease, stroke, and Alzheimer's disease.

Study Details

Overview

This study evaluates transcranial direct current stimulation (tDCS) as a potential treatment for motor dysfunction in Progressive Supranuclear Palsy (PSP). PSP is a progressive neurodegenerative disorder characterized by vertical supranuclear gaze palsy, axial rigidity, postural instability, and bradykinesia. Despite extensive research, no disease-modifying treatments exist, making symptomatic management a critical area of investigation.

tDCS is a non-invasive brain stimulation technique that modulates cortical excitability through weak direct electrical currents delivered via electrodes placed on the scalp. The technique has shown promise in various neurological conditions including Parkinson's disease, stroke, and Alzheimer's disease.

Study Details

• NCT Number: NCT07291687
• Status: Recruiting
• Study Type: Interventional
• Intervention: tDCS (Transcranial Direct Current Stimulation)
• Conditions: PSP (Progressive Supranuclear Palsy)
• Phase: Not applicable (Medical device study)
• Allocation: Randomized

Background

tDCS Mechanism of Action

tDCS works through several mechanisms:

Rationale for PSP

In PSP, motor dysfunction manifests as:

• Bradykinesia: Slowness of voluntary movements
• Axial rigidity: Stiffness of trunk and neck muscles
• Postural instability: Impaired balance and increased fall risk
• Gait disturbance: Shuffling gait with reduced arm swing

Previous Evidence

Research on tDCS in PSP has yielded mixed results:

Positive findings:

• Language improvement with tDCS over dorsolateral prefrontal cortex (DLPFC)[@cabre2019]
• Improved walking speed with 4 mA tDCS[@roncelo2021]
• Enhanced cognitive function in some studies

• A 2024 randomized, double-blinded, sham-controlled trial found no effectiveness of prefrontal tDCS in PSP[@cappiello2024]

Study Objectives

Primary Objectives

Secondary Objectives

Treatment Protocol

Study Design

• Randomized, double-blind, sham-controlled design
• Active tDCS vs. sham stimulation
• Parallel group assignment

Stimulation Parameters (Typical)

• Current intensity: 1-2 mA (or 4 mA based on emerging evidence)
• Duration: 20-30 minutes per session
• Electrode placement: Motor cortex (M1) targeting primary motor and premotor areas
• Session schedule: Multiple sessions over 2-4 weeks
• Total sessions: 10-20 sessions

Outcome Measures

Motor assessments:

• Unified Parkinson's Disease Rating Scale (UPDRS) Part III
• PSP Rating Scale (PSPRS)
• Timed Up and Go (TUG) test
• 10-Meter Walk Test
• Berg Balance Scale

• MoCA (Montreal Cognitive Assessment)
• Trail Making Test
• Stroop Test

• PDQ-39
• PSP Quality of Life Questionnaire

Eligibility Criteria

Inclusion Criteria

• Diagnosis of clinically definite or probable PSP
• Age 40-85 years
• Stable medication regimen for at least 4 weeks
• No contraindications to tDCS (see below)
• Ability to provide informed consent

Exclusion Criteria

• tDCS contraindications:
• Metal implants in the head
• Seizure history
• Active epilepsy
• Skin lesions at electrode sites
• Pacemaker or other electronic devices
• Significant psychiatric comorbidity
• Severe cognitive impairment preventing participation
• Orthopedic conditions limiting motor assessment

Safety Profile

tDCS is generally well-tolerated with a favorable safety profile:

Common Side Effects (typically mild)

• Scalp tingling or itching at electrode sites
• Mild headache
• Transient skin redness
• Fatigue

Rare Adverse Events

• Skin irritation or burns (rare with proper protocols)
• Mood changes
• Sleep disturbances

Clinical Significance

tDCS offers several potential advantages as a therapeutic approach:

Non-Invasiveness

Adjunctive Potential

• Standard pharmacological treatments
• Physical therapy
• Cognitive rehabilitation

Accessibility

• Home-based treatment protocols
• Cost-effective healthcare delivery
• Broader patient access

Disease Modification

See Also

• [Progressive Supranuclear Palsy](/diseases/progressive-supranuclear-palsy)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Transcranial Direct Current Stimulation](/therapeutics/tdcs)
• [Non-invasive Brain Stimulation](/mechanisms/non-invasive-brain-stimulation)

External Links

• [ClinicalTrials.gov: NCT07291687](https://clinicaltrials.gov/study/NCT07291687)
• [PubMed: tDCS and PSP](https://pubmed.ncbi.nlm.nih.gov/?term=tDCS+PSP+progressive+supranuclear+palsy)
• [tDCS Research Database](https://clinicaltrials.gov/search?cond=PSP&intr=tDCS)

References

tDCS in Other Neurodegenerative Conditions

Parkinson's Disease

tDCS has been more extensively studied in PD:

• Motor cortex stimulation improves UPDRS-III scores
• Prefrontal tDCS may enhance cognitive function
• Evidence for gait and balance benefits
• Cumulative effects with repeated sessions

Alzheimer's Disease

tDCS research in AD focuses on:

• Cognitive enhancement (memory, attention)
• Neural plasticity modulation
• Combination with cognitive training
• Disease-modifying potential through neurotrophic effects

Amyotrophic Lateral Sclerosis

tDCS studies in ALS are limited:

• Motor cortex stimulation safety established
• Potential for maintaining function
• Need for larger trials

Technical Parameters and Optimization

Electrode Configuration

Standard Montages

Current Density

• Target: 0.029-0.08 mA/cm²
• Session duration: 20-30 minutes
• Typical current: 1-2 mA (up to 4 mA in research)

Session Protocols

Acute Protocol

• Single session administration
• Immediate effects assessment
• Useful for proof-of-concept

Chronic Protocol

• Multiple sessions over 2-6 weeks
• Sustained effects evaluation
• Optimal for therapeutic trials

Individual Factors Affecting Response

| Factor | Effect on Response |
|--------|-------------------|
| Age | Older age may reduce plasticity |
| Disease severity | More severe disease may reduce response |
| Genetics | BDNF Val66Met affects outcomes |
| Medication | Dopaminergic drugs may enhance effects |
| Cognitive reserve | Higher reserve may improve benefits |

Comparison with Other Neuromodulation Approaches

tDCS vs. tACS (Transcranial Alternating Current Stimulation)

• tDCS: Direct current, primarily modulates excitability
• tACS: Alternating current, entrains neural oscillations
• Different mechanisms: tDCS affects resting membrane potential, tACS affects synchrony

tDCS vs. rTMS (Repetitive Transcranial Magnetic Stimulation)

| Feature | tDCS | rTMS |
|---------|------|------|
| Invasiveness | Non-invasive | Non-invasive |
| Mechanism | Neuromodulation | Neurostimulation |
| Spatial resolution | Broader | More focal |
| Pain | Minimal | Some discomfort |
| Cost | Lower | Higher |

tDCS vs. Deep Brain Stimulation

• DBS: Invasive, requires surgery
• tDCS: Non-invasive, surface electrodes
• DBS effects: More potent, direct
• tDCS advantages: Safer, easier to implement

Future Directions in tDCS Research

Novel Approaches

Emerging Applications

• Prevention trials: Targeting pre-symptomatic individuals
• Combination therapies: tDCS with disease-modifying drugs
• Home-based treatment: Remote tDCS protocols
• Pediatric applications: Early-onset neurodegeneration