Clinical trial NCT04116177: Flexible vs. Standard Deep Brain Stimulation Programming in Parkinson Disease Patients
Official title: Flexible vs. Standard Programming in Parkinson's Disease Patients Receiving Subthalamic Implant: a Double-blind Cross-over Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Parkinson Disease
Keywords: Deep brain stimulation
Parkinson disease
Novel strategies
Lead sponsor: University of Toronto
Sponsor class: OTHER
First posted: 2019-10-04
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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:

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change of Overall Global functioning (PGIC)
timeFrame: After 3 months of each intervention
Secondary outcomes:
measure: Measure of Quality of life (PDQ-39)
timeFrame: After 3 months of each intervention
measure: Clinical change in motor symptoms using Unified Parkinson Disease Rating Scale I-IV
timeFrame: After 3 months of each intervention
measure: Clinical change in motor symptoms
timeFrame: After 3 months of each intervention
measure: Number of falls
timeFrame: After 3 months of each intervention
measure: Change in the presence and severity of depressive symptoms using the Beck Depression Inventory (BDI)
timeFrame: After 3 months of each intervention
measure: Walking speed measure using Prokinetics gait analysis/Zeno Walkway
timeFrame: After 3 months of each intervention
measure: Step length measured using Prokinetics gait analysis/Zeno Walkway
timeFrame: After 3 months of each intervention
measure: Cadence measured using Prokinetics gait analysis/Zeno Walkway
timeFrame: After 3 months of each intervention
measure: Double support time measured using Prokinetics gait analysis/Zeno Walkway
timeFrame: After 3 months of each intervention
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Movement disorders Centre, Toronto Western Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
Study officials:
References:
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citation: Barbe MT, Maarouf M, Alesch F, Timmermann L. Multiple source current steering--a novel deep brain stimulation concept for customized programming in a Parkinson's disease patient. Parkinsonism Relat Disord. 2014 Apr;20(4):471-3. doi: 10.1016/j.parkreldis.2013.07.021. Epub 2013 Sep 14. No abstract available.
citation: Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology. 1967 May;17(5):427-42. doi: 10.1212/wnl.17.5.427. No abstract available.
citation: Jenkinson C, Fitzpatrick R, Peto V, Greenhall R, Hyman N. The Parkinson's Disease Questionnaire (PDQ-39): development and validation of a Parkinson's disease summary index score. Age Ageing. 1997 Sep;26(5):353-7. doi: 10.1093/ageing/26.5.353.
citation: Timmermann L, Jain R, Chen L, Maarouf M, Barbe MT, Allert N, Brucke T, Kaiser I, Beirer S, Sejio F, Suarez E, Lozano B, Haegelen C, Verin M, Porta M, Servello D, Gill S, Whone A, Van Dyck N, Alesch F. Multiple-source current steering in subthalamic nucleus deep brain stimulation for Parkinson's disease (the VANTAGE study): a non-randomised, prospective, multicentre, open-label study. Lancet Neurol. 2015 Jul;14(7):693-701. doi: 10.1016/S1474-4422(15)00087-3. Epub 2015 May 28.