CANadian Adaptive DBS TriAl

Study Overview
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Brief Summary
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Parkinsonian symptoms, such as freezing of gait (FOG) or hypophonia, play a significant role in reducing quality of life for Parkinson disease (PD) patients, and are poorly responsive or can worsen with deep brain stimulation (DBS). Repeated adjustments of stimulation parameters may be beneficial however, continuous DBS (cDBS) does not adapt to the patients' rapidly fluctuating clinical status and does not take into account reliable and consistent state-trait biomarkers. These biomarkers can be recorded by the electrode itself as local field potentials (LFP). These LFPs can be used to guide stimulation output by means of a 'closed loop' or 'adaptive' DBS (aDBS). This is a pilot, two-phase, double-blinded, cross-over study of chronic Adaptive vs. Continuous STN DBS in patients with PD by using a novel implantable DBS system that can automatically adjust stimulation parameters based on the patient's clinical condition. The study will test the hypothesis that aDBS stimulation will treat motor fluctuations similarly to continuous stimulation but it will be superior to the latter in the treatment of speech, gait impairment and falls.

Official Title
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Adaptive/Closed Loop vs. Continuous/Open Loop Deep Brain Stimulation of Subthalamic Nucleus: a Two-Phase, Cross-Over, Double-Blind Trial in Patients With Parkinson's Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Device: Adaptive DBS
* Device: Continuous DBS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PD treated with bilateral STN DBS using Medtronic lead Able to provide informed consent and comply with study protocol Need to replace the implantable pulse generator (IPG) due to battery end of life Presence of disabling gait and/or balance and/or speech issues, as clinically judged by the PI and the patient Evidence that these disabling gait and/or balance and/or speech issues are worsened by DBS, i.e. they improve after turning DBS off. Use of contact 1 and/or 2 on one hemisphere and/or 9 and/or 10 on the other one Good LFP signal (assessable only after IPG replacement with Percept) in at least one hemisphere Exclusion Criteria: Previous DBS surgery without Medtronic products Potential use of any therapeutic stimulation configuration (such as bipolar) during the study which will prevent the use of aDBS Presence of any other disorders potentially impacting the outcome measures (e.g. orthopaedic issues) Medically unstable Severe non-motor problems, such as depression, dementia, etc.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

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 |
| --- | --- |
| Other: Continuous DBS<br> | Device: Continuous DBS<br>* aDBS vs cDBS<br>|
| Active Comparator: Adaptive DBS<br> | Device: Adaptive DBS<br>* aDBS vs cDBS<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Activities of Daily Living using the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part II | Unified Parkinson's Disease Rating Scale (MDS-UPDRS) II: Motor Aspects of Experiences of Daily Living (M-EDL), range 0-52. Lower scores reflect better motor experience. | Baseline, 5 months after IPG change, 8 months after battery change | 
| Change in Quality of Life (QoL) using Parkinson's Disease Questionnaire (PDQ39) | Parkinson's Disease Questionnaire (PDQ39): 8 dimensions, 5-point ordinal scoring system, each dimension total score range from 0 to 100. Lower scores reflect better QoL. | Baseline, 5 months after IPG change, 8 months after battery change | 
| Change in Gait using the Zeno Walkway by Protokinetics | Gait analysis (off and on medication) using the Zeno Walkway by Protokinetics. | Baseline, 5 months after IPG change, 8 months after battery change | 
| Change in Speech Quality using the Praat software (Phonetic Sciences) | Phonetic speech analysis (off and on medication) using the Praat software (Phonetic Sciences, Amsterdam, The Netherlands). Increased phonation reflects better speech quality. | Baseline, 5 months after IPG change, 8 months after battery change | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Motor Outcomes (adaptive DBS vs continuous DBS arms) using Unified Parkinson's Disease Rating Scale part III (motor examination) | Unified Parkinson's Disease Rating Scale motor examination (MDS-UPDRS III) score, range 0-132. Lower scores reflect less motor impairment. | Baseline, 2-5 months after IPG change, 8 months after battery change |