Safety and Efficacy of Adaptive Deep Brain Stimulation

Study Overview
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Brief Summary
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The aim of this study is to assess the safety and the potential efficacy of personalized Local Field Potential (LFP)-based adaptive Deep Brain Stimulation (aDBS), using the implantable pulse generator (IPG) of the AlphaDBS System, in Parkinson's Disease patients, chronically implanted in subthalamic nucleus (STN) for DBS, at the time of IPG replacement.

Detailed Description
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The study protocol is organized in two phases: the short-term follow-up and the long-term follow-up. PD patients in need of IPG replacement will be screened for enrollment eligibility. For the short-term follow-up, randomized patients will undergo 2 days of experimental sessions (i.e. one per each type of stimulation mode, cDBS and aDBS), in a well-controlled environment (i.e. during hospitalization). This part of the study will collect information on safety and potential efficacy endpoints as assessed by experienced neurologists. The short term follow-up phase will be considered complete when the endpoint assessment has been performed for all patients. Patients, who will not experience severe side effects and who will be deemed suitable by the neurologist, will be eligible to continue in the long-term follow-up phase (i.e. 1 month) in their home environment. The AlphaDBS System will deliver the stimulation in aDBS or cDBS mode, for two weeks in each mode.

Official Title
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A Double-blind Crossover Study to Evaluate the Safety and Efficacy of Adaptive Deep Brain Stimulation Delivered Through AlphaDBS System in Patients With Parkinson's Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Device: AlphaDBS System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of idiopathic PD; Subject is bilaterally treated with DBS in the STN using a Medtronic Activa PC or Activa RC IPG (mono-channnel or dual channel); DBS implant for at least 3 years and in need of battery replacement within 12 months after consent; Patients must be able to understand and sign the informed consent document Exclusion Criteria: Patients with severe cognitive decline, as resulting from MoCA assessment (MoCA score < 10); Patients with major psychiatric issues or any other condition that, based on the physician opinion, could interfere with the study conduct (e.g. severe depression, psychosis, etc.); Patients with any medical conditions potentially interfering with DBS battery replacement surgery (e.g. severe hypertension, active cancer, intake of drugs interfering with the coagulation etc.); Need to replace or reposition the leads during the IPG replacement procedure; Patients with > 10 recurrent falls experienced in the 3 months prior to consent; Patients that cannot tolerate an interruption of DBS stimulation for at least 30 min; Patients taking less than one levodopa dose per day; Patients without suitable LFPs recordings or with significant artifacts; Pregnant or breastfeeding women.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: conventional DBS<br> | Device: AlphaDBS System<br>* AlphaDBS can be programmed with two different types of stimulation: conventional DBS and adaptive DBS, that automatically adjusts the energy delivered to patient using a biosignal, local field potential (LFP), in a close loop configuration.<br>|
| Experimental: adaptive DBS<br> | Device: AlphaDBS System<br>* AlphaDBS can be programmed with two different types of stimulation: conventional DBS and adaptive DBS, that automatically adjusts the energy delivered to patient using a biosignal, local field potential (LFP), in a close loop configuration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of the AlphaDBS System, when used in cDBS and aDBS mode | Occurrence of device related adverse events | 1 month | 
| Change in the TEED to the patient | Change in the Total Electrical Energy Delivered (TEED) to the patient | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PD-related motor symptoms and their fluctuations | Evaluation of PD-related motor symptoms using the Unified Parkinson's Disease Rating Scale - UPDRS Part III. | 1 month | 
| Dyskinesia | Evaluation of dyskinesia and their fluctuations through repeated clinical assessments using the Unified Dyskinesia Rating Scale - UDysRS | 1 month | 
| Dyskinesia | Evaluation of the performance of a wearable accelerometer in detecting dyskinesia (compared to patient reported dyskinesia in the patient diary) | up to 1 month | 
| Time on with and without dyskinesia | Evaluation of time on with and without dyskinesia, assessed through Patient Diary | 1 month | 
| Time off | Evaluation of time off, assessed through Patient Diary | 1 month | 
| Patient controller usability | Usability will be evaluated by means of a usability questionnaire | 1 month | 
| Usability of the system for the physician | Usability will be evaluated by means of a usability questionnaire | 1 month |