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

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

Exploring the benefits of the linear lead in deep brain stimulation.

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:

1. 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).
2. 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.

Inclusion Criteria:

1) Patients with a diagnosis of PD according to the British Parkinson's Disease Society

1. 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)
2. 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)
3. Patients considered as STN-DBS candidates as per current standard of care. These patients will subsequently undergo STN-DBS surgery and maintain stimulation therapy.
4. Quality of life and social functioning influenced by levodopa-responsive signs
5. No major comorbidities

Exclusion Criteria:

1) Exclusion criteria will include patients with other significant neurologic or psychiatric illnesses or cognitive deficit.