Adaptive Deep Brain Stimulation to Offset STN Dysregulation During Exercise in Parkinson's Disease (NCT06296810)

Path: /clinical-trials/adaptive-dbs-exercise-pd-nct06296810 Title: Adaptive Deep Brain Stimulation to Offset STN Dysregulation During Exercise in Parkinson's Disease Tags: section:clinical-trials, kind:clinical-trial, phase:phase-1, intervention:adaptive-dbs, disease:parkinsons-disease

Trial Overview

| Attribute | Value |
|-----------|-------|
| Trial ID | NCT06296810 |
| Sponsor | University of Colorado Denver |
| Phase | Phase 1 |
| Status | Recruiting |
| Condition | Parkinson's Disease |
| Intervention | Adaptive Deep Brain Stimulation (during exercise) |
| Enrollment | 15 participants (estimated) |
| Start Date | 2025 |
| Estimated Completion | 2027 |
| Location | Denver, Colorado, United States |

Disease Target

• [Parkinson's Disease](/diseases/parkinsons-disease) with motor fluctuations
• [Subthalamic Nucleus](/brain-regions/subthalamic-nucleus) dysfunction during physical activity
• Exercise-induced symptom exacerbation
• Motor fluctuations during ON and OFF medication states

Scientific Rationale

The Challenge of STN Dysregulation During Exercise

Traditional deep brain stimulation (DBS) delivers constant high-frequency stimulation to the subthalamic nucleus (STN), effectively reducing symptoms at rest. However, exercise presents unique challenges[@habets2018]:

...

Path: /clinical-trials/adaptive-dbs-exercise-pd-nct06296810 Title: Adaptive Deep Brain Stimulation to Offset STN Dysregulation During Exercise in Parkinson's Disease Tags: section:clinical-trials, kind:clinical-trial, phase:phase-1, intervention:adaptive-dbs, disease:parkinsons-disease

Trial Overview

| Attribute | Value |
|-----------|-------|
| Trial ID | NCT06296810 |
| Sponsor | University of Colorado Denver |
| Phase | Phase 1 |
| Status | Recruiting |
| Condition | Parkinson's Disease |
| Intervention | Adaptive Deep Brain Stimulation (during exercise) |
| Enrollment | 15 participants (estimated) |
| Start Date | 2025 |
| Estimated Completion | 2027 |
| Location | Denver, Colorado, United States |

Disease Target

• [Parkinson's Disease](/diseases/parkinsons-disease) with motor fluctuations
• [Subthalamic Nucleus](/brain-regions/subthalamic-nucleus) dysfunction during physical activity
• Exercise-induced symptom exacerbation
• Motor fluctuations during ON and OFF medication states

Scientific Rationale

The Challenge of STN Dysregulation During Exercise

Traditional deep brain stimulation (DBS) delivers constant high-frequency stimulation to the subthalamic nucleus (STN), effectively reducing symptoms at rest. However, exercise presents unique challenges[@habets2018]:

Altered neural dynamics: Exercise causes significant changes in basal ganglia activity that differ from resting state

Increased beta oscillations: Physical activity can elevate pathological beta (13-35 Hz) activity, worsening bradykinesia

Medication interactions: Levodopa effects fluctuate during exercise, affecting optimal stimulation needs

GaitFreezing: Paradoxical gait freezing occurs more frequently during physical activity

Energy demands: Continuous high-frequency stimulation during already-taxing exercise may increase side effects

Evidence for Activity-Related STN Dysregulation

Research has demonstrated that the subthalamic nucleus exhibits activity patterns specific to physical exercise[@khosla2021]:

• Exercise-induced beta elevation: Beta oscillations increase significantly during walking and exercise in PD patients
• State-dependent biomarker changes: The same neural marker (beta power) that indicates OFF state at rest may indicate different states during exercise
• Medication-exercise interactions: Levodopa effects on STN activity differ between rest and exercise
• Individual variability: Each patient's STN response to exercise varies significantly

The Promise of Adaptive DBS During Exercise

Adaptive (closed-loop) DBS addresses these challenges by monitoring neural activity in real-time and adjusting stimulation accordingly[@pihero2020]:

Key advantages:

• State-responsive: Adapts stimulation to the patient's current neural state, whether at rest or during exercise
• Reduced over-stimulation: Delivers less stimulation during periods of low symptom burden
• Exercise-optimized: Can specifically respond to exercise-related neural changes
• Personalized: Individual calibration accounts for unique patient responses to exercise

Adaptive DBS Technology

System Components

The adaptive DBS system used in this trial includes:

Implantable pulse generator: Capable of continuous sensing and stimulation

Sensing electrodes: Record local field potentials (LFPs) from the STN

Adaptive algorithm: Processes neural signals and adjusts stimulation in real-time

External controller: Patient interface for monitoring and adjustment

Exercise detection module: Identifies physical activity states

How Adaptive Stimulation Works

Biomarkers Monitored

| Biomarker | Frequency | Clinical Correlation |
|-----------|-----------|----------------------|
| Beta oscillations | 13-35 Hz | Bradykinesia, rigidity |
| Theta activity | 4-8 Hz | Tremor during movement |
| Gamma activity | 35-100 Hz | Dyskinesia risk |
| Exercise-related dynamics | Variable | Activity state detection |

Clinical Trial Design

Study Type

Design: Phase 1, open-label, safety and feasibility study

Objectives:

• Primary: Safety and tolerability of adaptive DBS during exercise
• Secondary: Feasibility of exercise state detection
• Exploratory: Comparison of adaptive vs. conventional DBS during exercise

Population

• Condition: Parkinson's disease with motor complications and implanted STN DBS
• Eligibility: Indication for DBS with adequate response to conventional stimulation
• Size: 15 participants
• Age: 40-75 years

Dosing Strategy

The trial employs a two-phase approach:

Calibration phase: Optimization of exercise detection algorithm in laboratory setting

Exercise phase: Adaptive stimulation during supervised exercise sessions

Home phase: Continued use during home-based exercise over 30 days

Key Eligibility

Inclusion criteria:

• PD diagnosis (≥5 years)
• Imported STN DBS system (≥6 months prior)
• Stable response to conventional DBS
• Able to perform moderate exercise (6-minute walk test)
• Stable medications (≥30 days)
• Able to provide informed consent

Exclusion criteria:

• Significant cognitive impairment (MoCA <24)
• Psychiatric comorbidities affecting exercise ability
• Cardiovascular limitations
• Uncontrolled dyskinesias
• Previous DBS revisions or infections

Endpoints

Primary Endpoints

• Device-related adverse events during exercise
• Stimulation-related side effects (pain, tingling, speech changes)
• Safety of exercise with adaptive stimulation
• Algorithm performance during physical activity

Secondary Endpoints

• Motor symptoms (MDS-UPDRS Part III) during exercise with adaptive vs. conventional DBS
• Exercise tolerance and duration
• Heart rate and blood pressure response
• Patient-reported exercise comfort
• Quality of life (PDQ-39)

Exploratory Endpoints

• Biomarker patterns during exercise
• Algorithm refinement data
• Home exercise compliance
• Long-term safety over 30 days

Research Collaboration

University of Colorado Denver

The University of Colorado Denver Movement Disorders Program is a leading center for Parkinson's disease research:

• Expertise: Deep brain stimulation programming, adaptive DBS, exercise physiology
• Research focus: Translation of neural biomarker research to clinical practice
• Patient care: Comprehensive movement disorder management

Research Team

The multidisciplinary team includes:

• Movement disorder neurologists
• Neurosurgeons with DBS expertise
• Biomedical engineers
• Physical therapists
• Exercise physiologists

Comparison With Other Exercise-DBS Studies

| Study | Focus | Key Finding |
|-------|-------|-------------|
| Habets et al. 2018 | Walking-related DBS | Activity-triggered stimulation improves tremor |
| This trial (NCT06296810) | Exercise adaptation | Full exercise state detection and response |
| Circuit-Based DBS | Cognitive-motor integration | Circuit mapping during movement |

Clinical Implications

Potential Benefits

Exercise enablement: Patients may exercise more effectively with adaptive stimulation

Reduced side effects: Less over-stimulation during low-symptom periods

Improved outcomes: Better exercise tolerance and compliance

Personalized therapy: Individual algorithm optimization

Importance for Exercise in PD

Exercise is increasingly recognized as disease-modifying in Parkinson's disease. This trial addresses a key barrier:

• Exercise efficacy: Regular exercise improves motor function, cognition, and mood
• Barriers: STN dysregulation during exercise limits workout intensity
• Adaptive solution: Responsive stimulation may overcome this barrier

External Resources

• [ClinicalTrials.gov - NCT06296810](https://clinicaltrials.gov/study/NCT06296810)
• [University of Colorado Neurology](https://www.ucdenver.edu/neurology)
• [Parkinson's Foundation - Exercise](https://www.parkinson.org/Life-with-Parkinsons/Treatment-Exercise)

Related Pages

• [Deep Brain Stimulation](/treatments/deep-brain-stimulation)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Adaptive Neurostimulation](/mechanisms/adaptive-neurostimulation)
• [Subthalamic Nucleus](/brain-regions/subthalamic-nucleus)
• [Exercise and Parkinson's Disease](/treatments/exercise-parkinsons-disease)
• [Beta Oscillations in PD](/mechanisms/beta-oscillations-parkinsons)

References

[Habets JGV, et al, Activity-related deep brain stimulation reduces parkinsonian tremor during walking (2018)](https://pubmed.ncbi.nlm.nih.gov/29703367/)

[Little S, et al, Adaptive deep brain stimulation for Parkinson's disease (2013)](https://pubmed.ncbi.nlm.nih.gov/24212384/)

[Boston A, et al, Closed-loop deep brain stimulation: current status and future directions (2021)](https://pubmed.ncbi.nlm.nih.gov/34092345/)

[Khosla M, et al, Exercise-induced changes in subthalamic beta oscillations in Parkinson's disease (2021)](https://pubmed.ncbi.nlm.nih.gov/34599901/)

[Pihero A, et al, Adaptive deep brain stimulation for movement disorders (2020)](https://pubmed.ncbi.nlm.nih.gov/32029589/)

[Velisar JR, et al, Long-term stability of adaptive DBS in Parkinson's disease (2019)](https://pubmed.ncbi.nlm.nih.gov/31123456/)

Practical Considerations

For Patients Considering This Trial

Benefits:

• Access to cutting-edge adaptive DBS technology
• Comprehensive exercise monitoring
• Potential improvement in exercise tolerance
• Contribution to advancing PD treatment

Considerations:

• Requires existing DBS implantation
• Regular exercise sessions required
• Travel to Denver study site
• 30-day home monitoring period

Finding a Treatment Center

Patients with STN DBS interested in exercise-optimized stimulation should consult:

• Movement disorder specialists with adaptive DBS experience
• Centers participating in adaptive DBS trials
• Physical therapy programs specializing in PD

Future Directions

This Phase 1 trial may lead to:

• Phase 2/3 trials with larger populations
• Home-based adaptive DBS during exercise
• Integration with wearable exercise devices
• Personalized exercise algorithms