Clinical trial NCT03462082: 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
Overall status: COMPLETED
Phase: NA
Conditions: Parkinson Disease
Keywords: Parkinson's disease
axial motor dysfunction
asymmetric neuromodulation
subthalamic nucleus deep brain stimulation
Lead sponsor: University of Toronto
Sponsor class: OTHER
First posted: 2018-03-12
Enrollment: 22
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Change in Gait Velocity
timeFrame: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
Secondary outcomes:
measure: Change in Motor Function
timeFrame: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
measure: Change in Axial Motor Function (1)
timeFrame: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
measure: Change in Axial Motor Function (2)
timeFrame: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
measure: Change in Axial Motor Function (3)
timeFrame: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
measure: Change in Quantitative Gait Analysis (1)
timeFrame: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
measure: Change in Quantitative Gait Analysis (2)
timeFrame: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
measure: Change in Quantitative Gait Analysis (3)
timeFrame: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
measure: Change in Quantitative Speech Analysis (1)
timeFrame: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
measure: Change in Quantitative Speech Analysis (2)
timeFrame: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
measure: Change in Quantitative Speech Analysis (3)
timeFrame: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
measure: Change in Quantitative Speech Analysis (4)
timeFrame: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
measure: Change in Quality of Life
timeFrame: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
measure: Change in Select Cognitive Tasks
timeFrame: Baseline and 3 to 4 weeks after switching to each of the DBS conditions (Bilateral, Asymmetric 1, Asymmetric 2)
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, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.