Flexible vs. Standard Deep Brain Stimulation Programming in Parkinson Disease Patients

Study Overview
=================
Brief Summary
-----------------
Exploring the benefits of the linear lead in deep brain stimulation.

Detailed Description
-----------------
Detailed Description: This is a single-centre, double-blinded cross-over study comparing the 4 contact vs 8 contact electrodes of deep brain stimulation (DBS) patients. The study will follow 2 phases. Phase 1: Visit 1 Screening/Baseline (T0): As per current standard care for patients undergoing subthalamic deep brain stimulation (STN-DBS), participants will be screened 3-6 months before the surgery (T0) according to the inclusion/exclusion criteria. Visits for standard programming of VerciseTM system between 1 to 3 months after the surgery of 10 patients will be done in an open label fashion in order to find the best program for optimization of patient motor symptoms without side effects. This will be done according to the standard of practice currently adopted at Toronto Western Hospital. Phase 2: Visit 1 Randomization: 4 months +/- 4weeks of the surgery, patients will be randomized to two type of stimulation: Standard : only contacts 3-6 will be used in either unipolar or bipolar configuration; pulse width lower than 60μsec will not be used; all types of frequencies will be used but keeping the value constant for the both hemispheres at each active contact. The same amount of current for each of the active contacts will be used, however, in case of different currents at different contacts, an interleaved type of stimulation will be used and frequency will kept lower than 125Hz ( Fig 2A). Flexible : contacts 1-8 will be used in any possible configuration and using different amount of current for each of the active one as well as different frequencies; pulse width lower than 60μsec can be used. In conclusion, all the capabilities of the VerciseTM system will be used. Possible adjustments to stimulation parameters (e.g. Pulse width, amplitude threshold) will be performed to achieve an optimal therapeutic window for each patient. Visit 2 Follow up visit at 6 months +/- 4 weeks of the surgery for neurological examination if required. Visit 3 (T1): Cross over : 7 months +/- 4 weeks after the surgery patients will be switched to the other type of stimulation . Raters and patients will be blinded to the group allocation. Visit 4: Follow up visit at 9 months +/- 4 weeks of the surgery for neurological examination if required. Visit 5 (T2): End of study visit at month 10 +/- 4 weeks after the surgery. Raters and patients will be blinded to the group allocation. There might be unscheduled visits in case of unexpected clinical conditions (i.e. occurrence of side effects or worsening of motor conditions). Participants will be in this study for a maximum of 17 months. Throughout the whole study, participants will visit the clinic without their regular medication for PD as part of standard treatment practice. All the stimulation adjustment will be performed by the same unblinded physician using the GuideTM software provided by the company.

Official Title
-----------------
Flexible vs. Standard Programming in Parkinson's Disease Patients Receiving Subthalamic Implant: a Double-blind Cross-over Trial

Conditions
-----------------
Parkinson Disease

Intervention / Treatment
-----------------
* Device: Deep brain stimulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1) Patients with a diagnosis of PD according to the British Parkinson's Disease Society Brain Bank criteria (Hughes, Daniel, Kilford, & Lees, 1992), who fulfilled the inclusion and exclusion criteria proposed by the core assessment programme for surgical interventional therapies in PD panel (Defer, Widner, Marié, Rémy, & Levivier, 1999) Male and female patients with idiopathic PD, who have symptoms responsive to L-dopa medications, but who have significant impairment related to PD that is no longer well controlled with pharmacotherapy (i.e., refractory to optimized medical therapy) Patients considered as STN-DBS candidates as per current standard of care. These patients will subsequently undergo STN-DBS surgery and maintain stimulation therapy. Quality of life and social functioning influenced by levodopa-responsive signs No major comorbidities Exclusion Criteria: 1) Exclusion criteria will include patients with other significant neurologic or psychiatric illnesses or cognitive deficit.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Stimulation<br>Standard stimulation using contact 3-6 to achieve best therapeutic stimulation | Device: Deep brain stimulation<br>* Stimulation using VerciseTM system<br>|
| Experimental: Flexible stimulation<br>Flexible stimulation using all available stimulation strategies provided by the VerciseTM system including stimulation of contacts 1-8 and variable pulse width and frequency. | Device: Deep brain stimulation<br>* Stimulation using VerciseTM system<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Overall Global functioning (PGIC) | The PGIC evaluates all aspects of patients' health and assesses if there has been an improvement or decline in clinical status relative to baseline. This is a seven point scale with lower values indicating worsening and higher values, improvement. | After 3 months of each intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure of Quality of life (PDQ-39) | The PDQ-39 assesses individuals experiences across 8 dimensions of daily living. Each dimension is scored from 0 to 100. Lower scores mean better quality of life. | After 3 months of each intervention | 
| Clinical change in motor symptoms using Unified Parkinson Disease Rating Scale I-IV | The Unified Parkinson Disease Rating Scale I-IV ranges from 0-199, with higher scores meaning more severe disease | After 3 months of each intervention | 
| Clinical change in motor symptoms | Clinical change in motor symptoms as measured using falls diaries | After 3 months of each intervention | 
| Number of falls | Using a falls diary | After 3 months of each intervention | 
| Change in the presence and severity of depressive symptoms using the Beck Depression Inventory (BDI) | The BDI is a 21-question multiple-choice self-report inventory for measuring the severity of depression. Scores range from 0 to 63, with higher scores meaning worse depression. | After 3 months of each intervention | 
| Walking speed measure using Prokinetics gait analysis/Zeno Walkway | The Zeno Walkway is a 20 feet walking mat containing 16-pressure sensing pads and circuitry that allows for measurement of various gait and balance variables during straight walking. Patients will be asked to walk on the mat at a self selected pace. Walking speed will be measured. | After 3 months of each intervention | 
| Step length measured using Prokinetics gait analysis/Zeno Walkway | The Zeno Walkway is a 20 feet walking mat containing 16-pressure sensing pads and circuitry that allows for measurement of various gait and balance variables during straight walking. Patients will be asked to walk on the mat at a self selected pace. Mean and coefficients of variation (standard deviation divided by the mean x 100) of step length will be measured. | After 3 months of each intervention | 
| Cadence measured using Prokinetics gait analysis/Zeno Walkway | The Zeno Walkway is a 20 feet walking mat containing 16-pressure sensing pads and circuitry that allows for measurement of various gait and balance variables during straight walking. Patients will be asked to walk on the mat at a self selected pace. Mean and coefficients of variation (standard deviation divided by the mean x 100) of cadence will be measured. Cadence is the number of steps per minute of walking. | After 3 months of each intervention | 
| Double support time measured using Prokinetics gait analysis/Zeno Walkway | The Zeno Walkway is a 20 feet walking mat containing 16-pressure sensing pads and circuitry that allows for measurement of various gait and balance variables during straight walking. Patients will be asked to walk on the mat at a self selected pace. Mean and coefficients of variation (standard deviation divided by the mean x 100) of double support time will be measured. The double support time is the the time during gait where both feet are in contact to the ground | After 3 months of each intervention | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Deep brain stimulation, Parkinson disease, Novel strategies