Expanding the Therapeutic Window of Deep Brain Stimulation in Parkinson's Disease by Means of Directional Leads

Expanding the Therapeutic Window of Deep Brain Stimulation in Parkinson's Disease by Means of Directional Leads: a Double-blind Cross-over Pilot Study

Exploring directional lead

Study Overview

• Status: Unknown
• Conditions: Parkinson Disease
• Intervention / Treatment: Device: Deep brain stimulation

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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 2S8
      • Recruiting
      • Movement disorders Centre, Toronto Western Hospital
      • Contact: Alfonso Fasano, MD, PhD; Phone Number: 5961 +1 416 603 5800; Email: alfonso.fasano@uhn.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard Stimulation; Participants will receive stimulation using the best contact combination in ring mode.	Device: Deep brain stimulation; Steered stimulation using directional leads
Experimental: Directional Stimulation; Participants will receive stimulation using the best segmented (steered) contacts.	Device: Deep brain stimulation; Steered stimulation using directional leads

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number/incidence of adverse events	Number/incidence of adverse events	Throughout the study, averaging 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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
Patients Global Impression of Change (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, lower values indicating worsening and higher values, improvement.	After 3 months of each intervention
Change in articulation rate of speech using a Phonetics Software	Sample speeches will be recorded and digitalized at 44,000Hz using a microphone and analyzed with a Phonetics software. Articulation rate is calculated as the number of syllables produced/total time without pauses.	After 3 months of each intervention
Change in dysfluency of speech using a Phonetics Software	Sample speeches will be recorded and digitalized at 44,000Hz using a microphone and analyzed ina Phonetics software. Dysfluency is calculated as percentage of dysfluent words/total number of words. Dysfluent words are defined as part-words, word or phrase repetitions, revisions, hesitations or fillers.	After 3 months of each intervention
Change in intelligibility of speech using a Phonetics Software	Sample speeches will be recorded and digitalized at 44,000Hz using a microphone and analyzed in a Phonetics software. Intelligibility is a subjective measure of speech quality, and will be measured by a single rater trained in speech-language pathology.	After 3 months of each intervention
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.	The MDS-UPDRS scores range from 0 to 272, with higher scores meaning more severe disease	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 measured with the 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 with the 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
Double support time measured with the 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
Cadence measured with the 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
Percentage of ON time without troublesome dyskinesias during waking hours	ON time without dyskinesias is defined as the period of time is which patients have good mobility, associated with a good response to treatments and without troublesome involuntary movements (dyskinesias). This will be measured as percentage of ON time during the waking hours of the day, Patients will complete 24-hours motor diaries during 3 consecutive days, in which they are asked to rate their motor functions every 30 minutes.	After 3 months of each intervention
Number of falls or near-falls	Participants will be asked to keep track of all falls and near-falls (an event in which a person feels a fall is imminent but avoids it by compensatory action, such as grabbing a nearby object or controlling the fall) on a written diary throughout the intervention period.	Collected after 3 months of each intervention, but assessing all intervention period, averaging 6 months
Change in levodopa equivalent daily dose (LEDD)	LEDD is calculated using a conversion formula to transform all medications used for treatment of Parkinson's disease to an equivalent dose of levodopa	After 3 months of each intervention
Measure of resting-state local field potentials and functional connectivity of the brain using magnetoencephalography (MEG)	MEG will be used to measure the average absolute power and the power spectrum density of neuronal activity of the brain, both measures will be used to assess the effect of deep brain stimulation on the functional activity and oscillatory synchronization of various movement-related areas of the brain.	After 3 months of each intervention

Collaborators and Investigators

• Sponsor: University of Toronto
• Investigators: Principal Investigator: Alfonso Fasano, MD, University of Toronto

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2018
• Primary Completion (Anticipated): May 15, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: September 7, 2019
• First Submitted That Met QC Criteria: September 16, 2019
• First Posted (Actual): September 18, 2019

Study Record Updates

• Last Update Posted (Actual): September 18, 2019
• Last Update Submitted That Met QC Criteria: September 16, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: deep brain stimulation
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: 17-5705

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes