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

Parkinson Disease Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04093544
• Other study ID #: 17-5705
• Status: Recruiting
• Phase: N/A
• Start date: May 15, 2018
• Est. completion date: December 31, 2020

Study information

• Verified date: September 2019
• Source: University of Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Exploring directional lead

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 31, 2020
• Est. primary completion date: May 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Device:
• Deep brain stimulation
Steered stimulation using directional leads

Locations

Country	Name	City	State
Canada	Movement disorders Centre, Toronto Western Hospital	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University of Toronto

Country where clinical trial is conducted

Canada, 

References & Publications (7)

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. — View 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. — View 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. Review. — View 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. — View Citation

Pollo C, Kaelin-Lang A, Oertel MF, Stieglitz L, Taub E, Fuhr P, Lozano AM, Raabe A, Schüpbach 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. — View Citation

Steigerwald F, Müller 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. — View Citation

Timmermann L, Jain R, Chen L, Maarouf M, Barbe MT, Allert N, Brücke T, Kaiser I, Beirer S, Sejio F, Suarez E, Lozano B, Haegelen C, Vérin 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number/incidence of adverse events	Number/incidence of adverse events	Throughout the study, averaging 6 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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