Back to resultsAsymmetric Subthalamic Deep Brain Stimulation for Axial Motor Dysfunction in Parkinson's Disease
Primary Purpose
Parkinson Disease
Status
Completed
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Asymmetric STN-DBS
Sponsored by
About this trial
This is an interventional treatment trial for Parkinson Disease focused on measuring Parkinson's disease, axial motor dysfunction, asymmetric neuromodulation, subthalamic nucleus deep brain stimulation
Eligibility Criteria
Inclusion Criteria:
- Patients with Parkinson's disease (PD) (previously diagnosed according to the UK brain bank criteria) who develop treatment-resistant postural instability gait dysfunction (PIGD) more than 6 months but less than 5 years after bilateral subthalamic nucleus deep brain stimulation (STN-DBS).
- Treatment-resistant PIGD will be defined as freezing of gait and UPDRS or MDS-UPDRS PIGD subscales of more than 6 points despite optimization of medications and bilateral STN-DBS programming.
Exclusion Criteria:
- Treatment-resistant PIGD less than 6 months or more than 5 years after STN-DBS surgery.
- PIGD responsive to optimization of medications and/or bilateral STN-DBS programming.
- Cognitive impairment or psychiatric comorbidities (including substance abuse) that would interfere with the informed consent process, study adherence or outcome assessments.
- Advanced PD or any other neurological, cardiovascular or musculoskeletal co-morbidities that would preclude or require assistance to complete the 10-meter walking test.
- Patients not able to comply with 4-week interval evaluations following their potential enrollment due to personal reasons.
- Serious illness (requiring systemic treatment and/or hospitalization) until subject either completes therapy or is clinically-stable on therapy, in the opinion of the site investigator, for at least 30 days prior to study entry.
- Inability or unwillingness of subject or legal guardian/representative to give written informed consent.
Sites / Locations
- Movement disorders Centre, Toronto Western Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
No Intervention
Experimental
Experimental
Arm Label
Baseline STN-DBS
Asymmetric STN-DBS 1
Asymmetric STN-DBS 2
Arm Description
Maintenance of baseline bilateral STN-DBS settings.
Unilateral 50% reduction of voltage (e.g. right side)
Unilateral 50% reduction of voltage (e.g. left side)
Outcomes
Primary Outcome Measures
Change in Gait Velocity
As measured during the 10-meter walk test. In this test, participants walk at their usual, regular pace over a total distance of 10 meters. The middle 6-meters (between the 2-meter and 8-meter marks) are timed to measure gait velocity during steady-state gait.
Secondary Outcome Measures
Change in Motor Function
As measured by the MDS-UPDRS (Movement Disorders Society Unified Parkinson's Disease Rating Scale), which is a clinical and research tool to measure symptoms and signs of Parkinson's disease. It has 4 parts: I (non-motor experiences of daily living), II (motor experiences of daily living), III (motor exam) and IV (motor complications). The MDS-UPDRS has 60 items, scored from 0-4 each. The minimum score is 0 and the maximum score is 240.
The MDS-UPDRS (motor) is Part III and measures motor signs. It has 28 items, scored from 0-4 each, so the minimum score is 0 and the maximum score is 112.
The MDS-UPDRS (axial motor) is composed of items 3.1 to 3.3a and 3.9 to 3.13 of Part III of the MDS-UPDRS and measures axial motor signs. It has 8 items, scored from 0-4 each, so the minimum score is 0 and the maximum score is 32.
In the MDS-UPDRS total, motor and axial motor sub-scales, lower scores indicate better symptoms/signs and higher scores indicate worse symptoms/signs, respectively.
Change in Axial Motor Function (1)
As measured by the Mini-BESTest. The Mini-BESTest is a shorter version of the BESTest (Balance Evaluation Systems Test). It is a clinical and research tool to measure balance control. The Mini-BESTest has 14 items, scored from 0-2 each, so the minimum score is 0 and the maximum score is 28. Lower scores indicate worse balance control and higher scores indicate better balance control.
Change in Axial Motor Function (2)
As measured by the UPDRS-PIGD sub-scale. The UPDRS-PIGD is the Postural Instability Gait Dysfunction (PIGD) sub-scale of the Unified Parkinson's Disease Rating Scale (UPDRS). It is a clinical and research tool to measure PIGD. The UPDRS-PIGD has 5 items, scored from 0-4 each, so the minimum score is 0 and the maximum score is 20. Lower scores indicate better PIGD and higher scores indicate worse PIGD.
Change in Axial Motor Function (3)
As measured by the Freezing of Gait Questionnaire. The Freezing of Gait Questionnaire is a clinical and research tool to measure freezing of gait. It has 6 items, scored from 0-4 each, so the minimum score is 0 and the maximum score is 24. Lower scores indicate better and higher scores indicate worse freezing of gait, respectively.
Change in Quantitative Gait Analysis (1)
Changes in gait velocity in m/s as measured by a quantitative gait analysis system (Zeno walkway).
Change in Quantitative Gait Analysis (2)
Changes in step length in cm (mean, right, left) as measured by a quantitative gait analysis system (Zeno walkway).
Step length difference = [right - left step length]
Change in Quantitative Gait Analysis (3)
Step length ratio = [right step length] / [left step length]
Step length symmetry = ([right - left step length] / [right + left step length])
Change in Quantitative Speech Analysis (1)
Changes in pitch in Hertz (Hz) as measured by the Praat software.
Change in Quantitative Speech Analysis (2)
Changes in loudness in decibels (dB) as measured by the Praat software.
Change in Quantitative Speech Analysis (3)
Changes in jitter measured in percentage by the Praat software. In this case, jitter is the percentage change in the stability of the frequency of speech tone (i.e. speech cycle-to-cycle frequency variation)
Change in Quantitative Speech Analysis (4)
Changes in shimmer measured in percentage by the Praat software. In this case, shimmer is the percentage change in the stability of the amplitude of speech tone (i.e. speech cycle-to-cycle amplitude variation)
Change in Quality of Life
As measured by the Total Score of the 39-item Parkinson's Disease Quality of Life Questionnaire (PDQ-39). The PDQ-39 is a clinical and research tool to measure quality of life in Parkinson's disease. It has 39 questions, which patients score as never (0% of the time), occasionally (25% of the time), sometimes (50% of the time), often (75% of the time) or always (100% of the time). The PDQ-39 Total Score or Summary Index is the average of the 39 questions, expressed. The minimum score is 0% (never) and the maximum score is 100% (always). Lower scores indicate better quality of life and higher scores indicate worse quality of life.
Change in Select Cognitive Tasks
Left brain cognitive function: Hopkins Verbal Learning Test-Revised: Total recall trials 1-3 (0-36), delayed recall (0-12); Phonemic Verbal Fluency (0-no max); Semantic Verbal Fluency (Animal cue) (0-no max); Letter 1-back and 2-back working memory tasks (0-100%). Right brain cognitive function: Brief Visual Memory Test-Revised: Total recall trials 1-3 (0-36), delayed recall (0-12); Computerized landmark line bisection (-10 to 10); Spatial 1-back and 2-back working memory tasks (0-100%). Ranges in parentheses. Line bisection: closer to 0 is more accurate. For the rest: higher values are better
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03462082
Brief Title
Asymmetric Subthalamic Deep Brain Stimulation for Axial Motor Dysfunction in Parkinson's Disease
Official Title
A Single-center, Randomized, Double-blinded, Double-crossover Trial of Asymmetric Subthalamic Deep Brain Stimulation for Axial Motor Dysfunction in Parkinson's Disease
Study Type
Interventional
2. Study Status
Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
March 14, 2018 (Actual)
Primary Completion Date
April 15, 2019 (Actual)
Study Completion Date
April 15, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Toronto
4. Oversight
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.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This single-center, randomized, quadruple-blinded, double-crossover comparative efficacy trial will study the effects of unilateral 50% voltage reduction in axial motor dysfunction for patients with Parkinson's disease that develop treatment-resistant postural stability gait dysfunction after bilateral subthalamic nucleus deep brain stimulation surgery.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease
Keywords
Parkinson's disease, axial motor dysfunction, asymmetric neuromodulation, subthalamic nucleus deep brain stimulation
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Baseline STN-DBS
Arm Type
No Intervention
Arm Description
Maintenance of baseline bilateral STN-DBS settings.
Arm Title
Asymmetric STN-DBS 1
Arm Type
Experimental
Arm Description
Unilateral 50% reduction of voltage (e.g. right side)
Arm Title
Asymmetric STN-DBS 2
Arm Type
Experimental
Arm Description
Unilateral 50% reduction of voltage (e.g. left side)
Intervention Type
Other
Intervention Name(s)
Asymmetric STN-DBS
Intervention Description
Asymmetric deep brain stimulation
Primary Outcome Measure Information:
Title
Change in Gait Velocity
Description
As measured during the 10-meter walk test. In this test, participants walk at their usual, regular pace over a total distance of 10 meters. The middle 6-meters (between the 2-meter and 8-meter marks) are timed to measure gait velocity during steady-state gait.
Time Frame
Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
Secondary Outcome Measure Information:
Title
Change in Motor Function
Description
As measured by the MDS-UPDRS (Movement Disorders Society Unified Parkinson's Disease Rating Scale), which is a clinical and research tool to measure symptoms and signs of Parkinson's disease. It has 4 parts: I (non-motor experiences of daily living), II (motor experiences of daily living), III (motor exam) and IV (motor complications). The MDS-UPDRS has 60 items, scored from 0-4 each. The minimum score is 0 and the maximum score is 240.
The MDS-UPDRS (motor) is Part III and measures motor signs. It has 28 items, scored from 0-4 each, so the minimum score is 0 and the maximum score is 112.
The MDS-UPDRS (axial motor) is composed of items 3.1 to 3.3a and 3.9 to 3.13 of Part III of the MDS-UPDRS and measures axial motor signs. It has 8 items, scored from 0-4 each, so the minimum score is 0 and the maximum score is 32.
In the MDS-UPDRS total, motor and axial motor sub-scales, lower scores indicate better symptoms/signs and higher scores indicate worse symptoms/signs, respectively.
Time Frame
Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
Title
Change in Axial Motor Function (1)
Description
As measured by the Mini-BESTest. The Mini-BESTest is a shorter version of the BESTest (Balance Evaluation Systems Test). It is a clinical and research tool to measure balance control. The Mini-BESTest has 14 items, scored from 0-2 each, so the minimum score is 0 and the maximum score is 28. Lower scores indicate worse balance control and higher scores indicate better balance control.
Time Frame
Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
Title
Change in Axial Motor Function (2)
Description
As measured by the UPDRS-PIGD sub-scale. The UPDRS-PIGD is the Postural Instability Gait Dysfunction (PIGD) sub-scale of the Unified Parkinson's Disease Rating Scale (UPDRS). It is a clinical and research tool to measure PIGD. The UPDRS-PIGD has 5 items, scored from 0-4 each, so the minimum score is 0 and the maximum score is 20. Lower scores indicate better PIGD and higher scores indicate worse PIGD.
Time Frame
Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
Title
Change in Axial Motor Function (3)
Description
As measured by the Freezing of Gait Questionnaire. The Freezing of Gait Questionnaire is a clinical and research tool to measure freezing of gait. It has 6 items, scored from 0-4 each, so the minimum score is 0 and the maximum score is 24. Lower scores indicate better and higher scores indicate worse freezing of gait, respectively.
Time Frame
Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
Title
Change in Quantitative Gait Analysis (1)
Description
Changes in gait velocity in m/s as measured by a quantitative gait analysis system (Zeno walkway).
Time Frame
Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
Title
Change in Quantitative Gait Analysis (2)
Description
Changes in step length in cm (mean, right, left) as measured by a quantitative gait analysis system (Zeno walkway).
Step length difference = [right - left step length]
Time Frame
Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
Title
Change in Quantitative Gait Analysis (3)
Description
Step length ratio = [right step length] / [left step length]
Step length symmetry = ([right - left step length] / [right + left step length])
Time Frame
Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
Title
Change in Quantitative Speech Analysis (1)
Description
Changes in pitch in Hertz (Hz) as measured by the Praat software.
Time Frame
Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
Title
Change in Quantitative Speech Analysis (2)
Description
Changes in loudness in decibels (dB) as measured by the Praat software.
Time Frame
Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
Title
Change in Quantitative Speech Analysis (3)
Description
Changes in jitter measured in percentage by the Praat software. In this case, jitter is the percentage change in the stability of the frequency of speech tone (i.e. speech cycle-to-cycle frequency variation)
Time Frame
Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
Title
Change in Quantitative Speech Analysis (4)
Description
Changes in shimmer measured in percentage by the Praat software. In this case, shimmer is the percentage change in the stability of the amplitude of speech tone (i.e. speech cycle-to-cycle amplitude variation)
Time Frame
Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
Title
Change in Quality of Life
Description
As measured by the Total Score of the 39-item Parkinson's Disease Quality of Life Questionnaire (PDQ-39). The PDQ-39 is a clinical and research tool to measure quality of life in Parkinson's disease. It has 39 questions, which patients score as never (0% of the time), occasionally (25% of the time), sometimes (50% of the time), often (75% of the time) or always (100% of the time). The PDQ-39 Total Score or Summary Index is the average of the 39 questions, expressed. The minimum score is 0% (never) and the maximum score is 100% (always). Lower scores indicate better quality of life and higher scores indicate worse quality of life.
Time Frame
Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
Title
Change in Select Cognitive Tasks
Description
Left brain cognitive function: Hopkins Verbal Learning Test-Revised: Total recall trials 1-3 (0-36), delayed recall (0-12); Phonemic Verbal Fluency (0-no max); Semantic Verbal Fluency (Animal cue) (0-no max); Letter 1-back and 2-back working memory tasks (0-100%). Right brain cognitive function: Brief Visual Memory Test-Revised: Total recall trials 1-3 (0-36), delayed recall (0-12); Computerized landmark line bisection (-10 to 10); Spatial 1-back and 2-back working memory tasks (0-100%). Ranges in parentheses. Line bisection: closer to 0 is more accurate. For the rest: higher values are better
Time Frame
Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with Parkinson's disease (PD) (previously diagnosed according to the UK brain bank criteria) who develop treatment-resistant postural instability gait dysfunction (PIGD) more than 6 months but less than 5 years after bilateral subthalamic nucleus deep brain stimulation (STN-DBS).
Treatment-resistant PIGD will be defined as freezing of gait and UPDRS or MDS-UPDRS PIGD subscales of more than 6 points despite optimization of medications and bilateral STN-DBS programming.
Exclusion Criteria:
Treatment-resistant PIGD less than 6 months or more than 5 years after STN-DBS surgery.
PIGD responsive to optimization of medications and/or bilateral STN-DBS programming.
Cognitive impairment or psychiatric comorbidities (including substance abuse) that would interfere with the informed consent process, study adherence or outcome assessments.
Advanced PD or any other neurological, cardiovascular or musculoskeletal co-morbidities that would preclude or require assistance to complete the 10-meter walking test.
Patients not able to comply with 4-week interval evaluations following their potential enrollment due to personal reasons.
Serious illness (requiring systemic treatment and/or hospitalization) until subject either completes therapy or is clinically-stable on therapy, in the opinion of the site investigator, for at least 30 days prior to study entry.
Inability or unwillingness of subject or legal guardian/representative to give written informed consent.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alfonso Fasano, MD, PhD
Organizational Affiliation
University of Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
Movement disorders Centre, Toronto Western Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T 2S8
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
To be shared as supplementary data upon publication of the results of the trial.
IPD Sharing Time Frame
To be shared as supplementary data upon publication of the results of the trial.
Citations:
PubMed Identifier
21370271
Citation
Fasano A, Herzog J, Seifert E, Stolze H, Falk D, Reese R, Volkmann J, Deuschl G. Modulation of gait coordination by subthalamic stimulation improves freezing of gait. Mov Disord. 2011 Apr;26(5):844-51. doi: 10.1002/mds.23583. Epub 2011 Mar 2.
Results Reference
background
PubMed Identifier
27278062
Citation
Lizarraga KJ, Jagid JR, Luca CC. Comparative effects of unilateral and bilateral subthalamic nucleus deep brain stimulation on gait kinematics in Parkinson's disease: a randomized, blinded study. J Neurol. 2016 Aug;263(8):1652-6. doi: 10.1007/s00415-016-8191-3. Epub 2016 Jun 8.
Results Reference
background
PubMed Identifier
29184712
Citation
Lizarraga KJ, Luca CC, De Salles A, Gorgulho A, Lang AE, Fasano A. Asymmetric neuromodulation of motor circuits in Parkinson's disease: The role of subthalamic deep brain stimulation. Surg Neurol Int. 2017 Oct 24;8:261. doi: 10.4103/sni.sni_292_17. eCollection 2017.
Results Reference
background
PubMed Identifier
35156734
Citation
Lizarraga KJ, Gnanamanogaran B, Al-Ozzi TM, Cohn M, Tomlinson G, Boutet A, Elias GJB, Germann J, Soh D, Kalia SK, Hodaie M, Munhoz RP, Marras C, Hutchison WD, Lozano AM, Lang AE, Fasano A. Lateralized Subthalamic Stimulation for Axial Dysfunction in Parkinson's Disease: A Randomized Trial. Mov Disord. 2022 May;37(5):1079-1087. doi: 10.1002/mds.28953. Epub 2022 Feb 13.
Results Reference
derived
Learn more about this trial
Asymmetric Subthalamic Deep Brain Stimulation for Axial Motor Dysfunction in Parkinson's Disease
We'll reach out to this number within 24 hrs