Closed-Loop Therapeutic Refinement Using Local Field Potentials in Parkinson's Disease

Not Applicable

Not yet recruiting

• Conditions: Parkinson's Disease (PD)

• Registration Number: NCT07105280
• Lead Sponsor: HagaZiekenhuis

Brief Summary

This multi-center pilot study compares conventional DBS (cDBS) and adaptive DBS (aDBS) in Parkinson's disease patients using the Medtronic Percept™ system.

The aim of the study is to identify which patients benefit most from aDBS, and to explore patient and LFP signal characteristics as well as stimulation parameters as potential predictors of treatment preference and efficacy. The study utilizes a blinded, randomized N-of-1 trial design, where each patient tests the following:

* Original cDBS settings (cDBS);

* Optimized cDBS settings (O-cDBS);

* Optimized aDBS settings (O-aDBS) Each setting is evaluated for a minimum of 2 and maximum of 7 days at home in a randomized order (patient blinded).

The main study outcome consists of the patient's final preference among the three DBS programs: original cDBS, O-cDBS, or O-aDBS. Secondary outcomes focus on differences between cDBS, O-cDBS and O-aDBS regarding the following parameters (among others):

* Quality of life (PDQ-39);

* Patient satisfaction (5-point Likert Scale);

* (Non)-motor fluctuations (MDS-UPDRS-III + MDS-NMS-Q);

* Time spent in "ON"/"OFF" motor phases (symptom diary + MDS-UPDRS IV);

* Time spent experiencing dyskinesia (symptom diary + MDS-UPDRS IV);

* Time spent with the most bothersome symptom (symptom diary + MDSUPDRS IV);

* Stimulation parameters;

* Local field potentials.

The study also incorporates real-world home-based assessments using the Experience Sampling Method (ESM) to capture motor and non-motor symptom fluctuations in daily life and identify differences among the three settings.

Detailed Description

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established treatment for patients with Parkinson's disease (PD), particularly for those experiencing motor fluctuations that do not respond adequately to medication. Optimal clinical outcomes depend on precise programming of stimulation parameters to effectively reduce motor symptoms, while avoiding side effects by minimizing stimulation of adjacent brain structures. During surgery, an electrode with eight contact points (1-3-3-1 design) is permanently implanted.

At the Haga Teaching Hospital, Maastricht UMC+, and Amsterdam UMC, the Medtronic Percept™ PC/RC system is commonly used for PD patients. This system provides not only stimulation but also the ability to record brain signals in the form of local field potentials (LFPs). This recording functionality can offer valuable insights for clinicians to fine-tune DBS parameters. For instance, elevated beta activity (13-35 Hz) in LFPs has been shown to correlate with the severity of symptoms such as rigidity and bradykinesia in PD patients.

In January 2025, a software update was introduced for the Percept™ system, enabling more advanced LFP measurements. This update allows the system to deliver adaptive DBS (aDBS), in which brain signals are used in real-time to continuously and automatically adjust stimulation amplitude. Although aDBS is a promising advancement, comprehensive research comparing its benefits and drawbacks to conventional DBS (cDBS) is still lacking. The only major study, ADAPT-PD, found that aDBS and cDBS result in similar durations of time spent in the "ON" phase, but it did not clarify which subgroup of patients benefits most from aDBS. Interestingly, many participants in the ADAPT-PD study expressed a desire to switch from cDBS to aDBS after the trial, though the factors influencing these preferences remain unclear. This highlights the need for detailed investigation into the relative advantages of aDBS and for whom the current form of aDBS provides the greatest benefit.

This study targets PD patients who have undergone cDBS for at least six months but are not experiencing optimal results due to persistent motor symptoms or stimulation-induced side effects that are insufficiently addressed by standard cDBS. Within this pilot study, using a combined N-of-1 trial design, outcomes of the patient's current cDBS settings and optimized conventional DBS (O-cDBS) will be objectively compared with those of optimized adaptive DBS (O-aDBS).

In an N-of-1 trial, an individual patient undergoes different test and placebo treatments in a randomized order. By conducting multiple N-of-1 trials across several patients, reliable and objective outcomes can be gathered both at the individual and population levels. In this study, each patient will test all three stimulation programs (current cDBS, O-cDBS, and O-aDBS) in a blinded and randomized sequence, each for seven days. The final outcome will be the patient's preferred program, with the patient's personal choice taking priority. To better understand the impact of switching from cDBS to aDBS-and to include effects on patient quality of life-this study will analyze not only motor symptoms but also cognitive and behavioral effects in daily life. This will be assessed through structured questionnaires, including a symptom diary and questions via the Experience Sampling Method (ESM). ESM is a validated, CE-certified digital diary method where patients provide feedback on the patient's symptoms at semi-random times, helping to reduce recall bias. By objectively analyzing the pros and cons of switching from cDBS to aDBS in these specific patient groups, this study aims to support neurologists in the clinical use of this new technology. Furthermore, the findings may contribute to more effective use of the system and ultimately to improved DBS treatment and quality of life for patients with Parkinson's disease.

Study Timeline

• Status Verified: 2025-07
• Study First Submitted: 2025-07-21
• Study First Submitted QC: 2025-07-29
• Study First Posted: 2025-08-05
• Last Update Submitted: 2025-09-30
• Study Start: 2025-10-01
• Last Update Posted: 2025-10-03
• Primary Completion: 2027-06-01
• Study Completion: 2027-06-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Patients with Parkinson's disease with bilateral DBS in the STN
• DBS surgery with implantation of the Percept™ PC/RC system performed at least 6 months ago
• Symptoms such as dysarthria, freezing, or ON-OFF fluctuations that are insufficiently controlled
• A usable LFP signal is present on at least one side

Exclusion Criteria

• Patients for whom switching to aDBS, operating the remote control independently, or making regular visits to the DBS center is deemed clinically unsafe or unreliable by the treating physician - for example, due to active or unstable cognitive or psychiatric conditions.
• High impedance, defective DBS electrodes, or insufficient LFP signal quality, or bilateral stimulation primarily on the most ventral or dorsal contact points, preventing proper functioning of aDBS.
• Patients who have objected to the use of their electronic health record data for medical scientific research.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Primary Outcome Measures

Name	Time	Method
Patient preference of DBS settings	after the three week trial phase of the study	The patient's choice for one of the three program options (standard cDBS, O-cDBS, or O-aDBS)

Secondary Outcome Measures

Name	Time	Method
Quality of life per DBS settings	Reported after each week with one of the DBS settings (at 7 days, 14 days and 21 days)	The 39 item Parkinson's Disease Questionnaire (PDQ-39) score for cDBS, O-cDBS, O-aDBS (score between 0 (good quality) and 100 (bad quality))
General Prompt Experience Sampling Method score per DBS settings	Reported average daily score within each week with one of the DBS settings (at 1-7 days, 8-14 days and 15-21 days)	Custom general prompt daily (non-)motor fluctuations questionnaire via Experience Sampling Method (ESM), with a score ranging from 0 (good) to 270 (poor)
Patient satisfaction per DBS settings	Reported after each week with one of the DBS settings (at 7 days, 14 days and 21 days)	5-point Likert scale score for patient satisfaction with cDBS, O-cDBS and O-aDBS (1=very dissatisfied; 2= dissatisfied; 3=neutral; 4=satisfied; 5=very satisfied)
Time spent in ON/OFF per DBS settings according to symptom diary	Reported after each week with one of the DBS settings (at 7 days, 14 days and 21 days)	Percentage of time spent in OFF during time awake for cDBS, O-cDBS and O-aDBS according to symptom diary (0% (good) to 100% (poor)).
Time spent with dyskinesia per DBS setting according to symptom diary	Reported after each week with one of the DBS settings (at 7 days, 14 days and 21 days)	Percentage of time awake spent with dyskinesia for cDBS, O-cDBS and O-aDBS according to symptom diary (0% (good), 100% (poor)).
Time spent with most bothersome symptom per DBS setting according to symptom diary	Reported after each week with one of the DBS settings (at 7 days, 14 days and 21 days)	Percentage of time awake spent with most bothersome symptom for cDBS, O-cDBS and O-aDBS according to symptom diary. (0% (good), 100% (poor))
Total score for motor fluctuations per DBS setting	Reported at baseline and after optimizing each intervention	Motor score according to Movement Disorder Society - Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) for cDBS, O-cDBS and O-aDBS, with the score ranging from 0 (good) to 132 (poor)
Levodopa equivalent daily dose per DBS setting	Reported after each week with one of the DBS settings (at 7 days, 14 days and 21 days)	According to latest levodopa equivalent daily dose scheme, determined for cDBS, O-cDBS and O-aDBS
Time spent in ON/OFF per DBS settings	Reported after each week with one of the DBS settings (at 7 days, 14 days and 21 days)	Percentage of time spent in OFF during time awake for cDBS, O-cDBS and O-aDBS according to Movement Disorder Society - Unified Parkinson's Disease Rating Scale Part IV (MDS-UPDRS-IV) for cDBS, O-cDBS and O-aDBS (0% (good) to 100% (poor)).
Time spent with dyskinesia per DBS setting	Reported after each week with one of the DBS settings (at 7 days, 14 days and 21 days)	Percentage of time awake spent with dyskinesia for cDBS, O-cDBS and O-aDBS according to Movement Disorder Society - Unified Parkinson's Disease Rating Scale Part IV (MDS-UPDRS-IV) (0% (good), 100% (poor))
Time spent with most bothersome symptom per DBS setting	Reported after each week with one of the DBS settings (at 7 days, 14 days and 21 days)	Percentage of time awake spent with most bothersome symptom for cDBS, O-cDBS and O-aDBS according to Movement Disorder Society - Unified Parkinson's Disease Rating Scale Part IV (MDS-UPDRS-IV) in case of symptom being either "Motor fluctuations", "Dyskinesia", "OFF- dystonia", (0% (good), 100% (poor)).
Total score for non-motor fluctuations per DBS setting	Reported at baseline and after optimizing each intervention	Non-motor score according to Movement Disorder Society - Non-Motor Symptom Questionnaire (MDS-NMS-Q) for cDBS, O-cDBS and O-aDBS, with scores ranging from 0 (good) to 208 (poor)).
Morning Prompt Experience Sampling Method score per DBS settings	Reported average daily score within each week with one of the DBS settings (at 1-7 days, 8-14 days and 15-21 days)	Custom morning prompt daily (non-)motor fluctuations questionnaire via Experience Sampling Method (ESM), with a score ranging from 0 (good) to 35 (poor)
Evening Prompt Experience Sampling Method score per DBS settings	Reported average daily score within each week with one of the DBS settings (at 1-7 days, 8-14 days and 15-21 days)	Custom evening prompt daily (non-)motor fluctuations questionnaire via Experience Sampling Method (ESM), with a score ranging from 0 (good) to 76 (poor)

Trial Locations

Locations (2)

Amsterdam UMC; 🇳🇱 Amsterdam, Netherlands

Maastricht UMC+; 🇳🇱 Maastricht, Netherlands