Clinical trial NCT04093544: Expanding the Therapeutic Window of Deep Brain Stimulation in Parkinson's Disease by Means of Directional Leads
Official title: Expanding the Therapeutic Window of Deep Brain Stimulation in Parkinson's Disease by Means of Directional Leads: a Double-blind Cross-over Pilot Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Parkinson Disease
Keywords: deep brain stimulation
Lead sponsor: University of Toronto
Sponsor class: OTHER
First posted: 2019-09-18
Enrollment: 20
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 directional lead

Detailed description: This is a single-centre, double-blinded cross-over study comparing the standard electrode configuration (ring-mode) vs. directional electrode configuration for steered stimulation 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 DBS STN implant surgery (T0) according to the inclusion/exclusion criteria.

Visits for standard practiced care for programing of DBS Between 1 to 3 months after the surgery, programing of the DBS system for the 20 patients will be done in an open label fashion in order to find the contact able to reduce the motor symptoms without the 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 after the surgery, patients will be randomized to two type of stimulation:

1. Standard : The percentage of current allocated to the central split contacts will be evenly distributed in order to perfectly mimic a standard ring contact. All possible types of frequencies and pulse widths will be used. The same amount of current for each of the active contacts will be used.
2. Directional: 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. In conclusion, all the capabilities of the DBS 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. 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 16 months. Throughout the whole study, participants will visit the clinic without their regular medication as part of standard treatment practice. All the stimulation adjustment will be performed by the same unblinded physician or sub-investigator.

Eligibility criteria: 1. Patients with a diagnosis of Parkinson's disease (PD) according to the British Parkinson's Disease Society Brain Bank criteria, who fulfilled the inclusion and exclusion criteria proposed by the core assessment programme for surgical interventional therapies in PD panel
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 subthalamic nucleus deep brain stimulation (STN-DBS) candidates as per current standard of care. These patients will subsequently undergo STN-DBS surgery and maintain stimulation therapy.
4. Patients aged 18 to 80 years.
5. Quality of life and social functioning influenced by levodopa-responsive symptoms 6) No major comorbidities

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

Primary outcomes:
measure: Number/incidence of adverse events
timeFrame: Throughout the study, averaging 6 months
Secondary outcomes:
measure: Change from baseline in a measure of health related quality of life and non-motor symptoms of Parkinson's disease using the Parkinson's disease Questionnaire (PDQ-39)
timeFrame: After 3 months of each intervention
measure: Patients Global Impression of Change (PGIC)
timeFrame: After 3 months of each intervention
measure: Change in articulation rate of speech using a Phonetics Software
timeFrame: After 3 months of each intervention
measure: Change in dysfluency of speech using a Phonetics Software
timeFrame: After 3 months of each intervention
measure: Change in intelligibility of speech using a Phonetics Software
timeFrame: After 3 months of each intervention
measure: Change in the Movement Disorders sponsored Unified Parkinson's disease Rating Scale (MDS-UPDRS), a measure of various motor and non-motor symptoms used to assess the clinical course of Parkinson's longitudinally.
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 measured with the Zeno Walkway
timeFrame: After 3 months of each intervention
measure: Step length measured with the Zeno Walkway
timeFrame: After 3 months of each intervention
measure: Double support time measured with the Zeno Walkway
timeFrame: After 3 months of each intervention
measure: Cadence measured with the Zeno Walkway
timeFrame: After 3 months of each intervention
measure: Percentage of ON time without troublesome dyskinesias during waking hours
timeFrame: After 3 months of each intervention
measure: Number of falls or near-falls
timeFrame: Collected after 3 months of each intervention, but assessing all intervention period, averaging 6 months
measure: Change in levodopa equivalent daily dose (LEDD)
timeFrame: After 3 months of each intervention
measure: Measure of resting-state local field potentials and functional connectivity of the brain using magnetoencephalography (MEG)
timeFrame: After 3 months of each intervention
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Movement disorders Centre, Toronto Western Hospital
state: Ontario
Study officials:
affiliation: University of Toronto
name: Alfonso Fasano, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fasano A, Daniele A, Albanese A. Treatment of motor and non-motor features of Parkinson's disease with deep brain stimulation. Lancet Neurol. 2012 May;11(5):429-42. doi: 10.1016/S1474-4422(12)70049-2.
citation: Herzog J, Pinsker M, Wasner M, Steigerwald F, Wailke S, Deuschl G, Volkmann J. Stimulation of subthalamic fibre tracts reduces dyskinesias in STN-DBS. Mov Disord. 2007 Apr 15;22(5):679-84. doi: 10.1002/mds.21387.
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: 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.
citation: Contarino MF, Bour LJ, Verhagen R, Lourens MA, de Bie RM, van den Munckhof P, Schuurman PR. Directional steering: A novel approach to deep brain stimulation. Neurology. 2014 Sep 23;83(13):1163-9. doi: 10.1212/WNL.0000000000000823. Epub 2014 Aug 22.
citation: Steigerwald F, Muller L, Johannes S, Matthies C, Volkmann J. Directional deep brain stimulation of the subthalamic nucleus: A pilot study using a novel neurostimulation device. Mov Disord. 2016 Aug;31(8):1240-3. doi: 10.1002/mds.26669. Epub 2016 May 31.
citation: Pollo C, Kaelin-Lang A, Oertel MF, Stieglitz L, Taub E, Fuhr P, Lozano AM, Raabe A, Schupbach M. Directional deep brain stimulation: an intraoperative double-blind pilot study. Brain. 2014 Jul;137(Pt 7):2015-26. doi: 10.1093/brain/awu102. Epub 2014 May 19.