Optimizing Adaptive DBS for Parkinson's Disease
ConditionPARKINSON DISEASE (Disorder)
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of California, Davis
About this trial
Parkinson's disease (PD) affects more than 10 million people worldwide and causes progressive motor symptoms such as slowness, stiffness and tremor. For patients whose symptoms are no longer adequately controlled with medication, deep brain stimulation (DBS) can substantially improve motor function. More recently, adaptive DBS (aDBS) has become available. Unlike conventional DBS, which delivers continuous stimulation, aDBS automatically adjusts stimulation in response to brain activity recorded by the implanted device.
Current clinical aDBS programming is based primarily on brief recordings obtained during clinic visits. However, Parkinson's symptoms and the underlying brain signals change throughout the day in response to medication, daily activities and other factors. As a result, recordings collected during a single clinic visit may not fully capture the neural activity that best reflects a patient's symptoms in everyday life.
The purpose of this study is to determine whether incorporating long-term brain recordings collected during daily life improves adaptive DBS programming and clinical outcomes. Participants will first undergo in-clinic testing to identify brain signals associated with their symptoms. Brain activity and symptoms will then be monitored during everyday life using the sensing capabilities of the implanted DBS device. Participants with suitable brain signals will enter a randomized, blinded crossover study comparing three stimulation approaches: conventional continuous DBS, adaptive DBS programmed using the current clinic-based approach and adaptive DBS programmed using both clinic and at-home recordings.
The study will compare the effects of these approaches on motor fluctuations and quality of life. It will also determine how frequently different brain signals occur in people with Parkinson's disease and how well they reflect motor symptoms, providing information that may improve future adaptive DBS therapies.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Subjects will be 18 and over
Clinical diagnosis of idiopathic Parkinson's disease (PD), consistent with MDS diagnostic criteria
Motor fluctuations in response to medication
Bilateral subthalamic nucleus (STN) DBS using a commercial sensing-enabled device
Disqualifiers
Atypical or secondary parkinsonism (e.g., multiple system atrophy, progressive supranuclear palsy, vascular parkinsonism)
Prior brain surgery other than STN DBS
Clinically significant cognitive impairment or dementia, defined as MoCA < 24 or equivalent, or lacking capacity to provide informed consent
Active psychiatric illness that could compromise safety or participation (e.g., uncontrolled depression, psychosis, severe anxiety disorder)
Trial design
Design model
Crossover
Treatments tested in this trial
aDBS-Extended (Medtronic Percept™)
DeviceAll parameters are derived from Steps 2-4. Amplitude modulation is based on individualized biomarker thresholds established through in-clinic and at-home testing, within the participant's effective stimulation amplitude range. Delivered via implanted Medtronic Percept™ DBS system using FDA-approved settings.
aDBS-Standard (Medtronic Percept™)
DeviceaDBS-Standard, with stimulation parameters optimized by an independent clinician using the current standard clinical programming procedure, with iterative programming across multiple visits as needed.
Continuous DBS (cDBS) - Active Control (Medtronic Percept™)
DeviceParticipants receive their clinically optimized continuous DBS settings without adaptive modulation. Adaptive DBS parameters are configured to maintain blinding, but stimulation amplitude remains fixed at the standard cDBS level. Active stimulation is delivered throughout the study via the implanted Medtronic Percept™ DBS system.
Treatment groups
35 Participants
are divided into 3 treatment groupsGroup A: aDBS-ExtendedExperimental treatment 1 intervention
Group B: aDBS-StandardActive comparator 1 intervention
Group C: Continuous DBS (cDBS) - Active ControlActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
Prevalence and Spectral Properties of STN Local Field Potential Peaks
Prevalence and spectral properties of STN local field potential (LFP) peaks (beta: 13-30 Hz; gamma: 60-90 Hz), and their modulation by dopaminergic medication state.
Time frame
Neural recordings obtained during 1 in-clinic session. For participants in Part 2, selected neural biomarker will be recorded for 14 days, and symptom and medication logs completed on 3 of those days. Events are recorded for predefined symptoms.2
Percent Time With Most Bothersome Motor Symptom
Percent time of the most bothersome motor symptom, assessed via electronic self-ratings (Oehrn et al., Nature Medicine, 2024). Primary outcome measures will be derived from nightly self-reports, including time spent with the most bothersome motor symptom (hours/day) and time awake (hours/day). The outcome is calculated as the percentage of waking hours spent with the most bothersome motor symptom (hours with symptom ÷ waking hours × 100).
Time frame
Daily assessment over each 1-week treatment block; repeated 8 times per condition over approximately 6 months.3
Severity of Most Bothersome Motor Symptom
Self-reported severity of the most bothersome motor symptom. Symptom severity (0-10 scale). Scores range from 0 (no symptoms) to 10 (worst possible symptoms); higher scores indicate worse outcome.
Time frame
Daily assessment over each 1-week treatment block; repeated 8 times per condition over approximately 6 months4
Quality of Life (EQ-5D-5L)
Quality of life will be assessed using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L), including the EQ Visual Analogue Scale (EQ VAS; range 0-100), with higher scores indicating better perceived health.
Time frame
Daily assessment over each 1-week treatment block; repeated 8 times per condition over approximately 6 monthsSecondary outcomes
1
Medication-Related Modulation of STN Local Field Potential Spectral Power
Subthalamic nucleus (STN) local field potential spectral power will be compared between ON- and OFF-medication states using cluster-based permutation testing across frequencies. Data will be pooled across movement and rest conditions and across two stimulation levels to identify medication-related spectral differences that are independent of movement state and stimulation level. For significant frequency clusters, the magnitude of the medication-related difference will be quantified using Cohen's d. The frequency or frequency range with the largest Cohen's d will be selected as the patient-specific neural biomarker for subsequent at-home analyses.
Time frame
During the in-clinic testing session2
Wearable-Derived Motor Symptoms Across DBS Conditions
During testing of the DBS algorithms, the effect on motor symptoms will be objectively assessed using a validated wrist-worn movement sensor during each treatment condition. A single wearable-derived motor measure will be selected for each participant based on their predefined most bothersome motor symptom (bradykinesia, dyskinesia, or tremor). Tremor, bradykinesia, and dyskinesia are quantified using validated proprietary algorithm-derived scores (reported in device-defined score units) calculated for consecutive 2-minute epochs. Differences in the selected wearable-derived motor measure across conventional DBS, standard adaptive DBS, and extended adaptive DBS will be evaluated at the group level using a linear mixed-effects model, with participant included as a random effect.
Time frame
Continuous wearable monitoring during each 1-week treatment block, repeated 8 times per condition over approximately 6 months.3
Regression of Wearable-Derived Motor Measures on Patient-Specific STN Neural Biomarker Activity
The patient-specific subthalamic nucleus (STN) neural biomarker identified during in-clinic testing will be recorded during daily life together with motor symptoms objectively assessed using a validated wrist-worn movement sensor. Tremor, bradykinesia, and dyskinesia are quantified using validated proprietary algorithm-derived scores (reported in device-defined score units) calculated for consecutive 2-minute epochs. Regression analyses will quantify the relationships between patient-specific STN neural biomarker activity and wearable-derived measures of tremor, bradykinesia, and dyskinesia, with the regression coefficients reported as the outcomes.
Time frame
At-home neural and wearable recordings over 14 days.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov