Asymmetric Targeted DBS for PD With PIGD

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to compare the effectiveness of the deep brain stimulation of asymmetric targets [subthalamic nucleus (STN) in the right hemisphere while globus pallidus interna (GPi) in the left] versus the bilateral STN for the treatment of Parkinson's disease (PD) with postural instability/gait difficulty (PIGD) in a randomized, double-blinded manner.

Detailed Description
-----------------
This is a double-blinded, randomized, controlled trial aiming at comparing the efficacy of asymmetric targets and bilateral STN DBS in treating PD with PIGD. After being informed about the study and potential risks, enrolled patients giving written informed consent will be screened to determine eligibility for study entry. Patients who meet the eligibility requirements will be randomized into two groups in a 1:1 ratio using a minimization randomization method in a double-blinded manner, and later undergo bilateral DBS surgery. One group of patients will receive stimulation of left GPi and right STN, while the other will receive STN stimulation bilaterally. The follow-up period will be one year, with corresponding clinical assessments completed at six months and one year postoperatively.

Official Title
-----------------
Deep Brain Stimulation of Asymmetric Targets Versus Bilateral Subthalamic Nucleus (STN) for Parkinson's Disease With Postural Instability/Gait Difficulty: a Prospective, Randomized, Double-blinded Trial

Conditions
-----------------
Parkinson Disease

Intervention / Treatment
-----------------
* Device: Deep brain stimulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: diagnosis of idiopathic Parkinson's disease postural instability/gait difficulty (PIGD) phenotypes in the on-medication condition Exclusion Criteria: Atypical parkinsonism History of stroke, encephalitis, neuroleptic uses, MRI scan with evidence of significant brain atrophy, lacunar infracts, or other conditions that might interfere with intracranial surgery Presence of cognitive, or psychiatric or other co-morbidities (e.g., dementia, epilepsy, cranial traumatism, brain tumor, schizophrenia, severe depression or bipolar disorder, personality disorder, etc.) that might interfere with the patient's ability to complete the evaluations or to provide informed consent Presence of anatomical abnormalities in the target region Clinically significant medical history that would increase pre-/post-operative complications Other conditions considered by the investigators that might interfere with the surgery procedure, the follow-ups, and the interpretation of the data

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: L-GPi/R-STN<br>Participants randomized in this arm will receive L-GPi/R-STN stimulation for 1 year. | Device: Deep brain stimulation<br>* active DBS with optimal stimulating parameters<br>|
| Active Comparator: Bi-STN<br>Participants randomized in this arm will receive bilateral STN stimulation for 1 year. | Device: Deep brain stimulation<br>* active DBS with optimal stimulating parameters<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in the Movement Disorder Society-sponsord Unified Parkinson's Disease Rating Scale Part III at 12 months | In the off-medication condition, scores could range from 0 (no movement symptoms) to 72 (severe movement symptoms). | Baseline and 12 months | 
| Change from Baseline in balance ability on the Burg Balance Scale (BBS) at 12 months | In the off-medication condition, the scores could range from 0 (severe balance problem) to 56 (no balance problem). | Baseline and 12 months | 
| Change from Baseline in the number of freezing episodes on the Timed Up and Go test at 12 months | in the off-medication condition | Baseline and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in completion time on the Timed Up and Go test at 12 months | in the off-medication condition | Baseline and 12 months | 
| Change from Baseline in completion time on the Timed Up and Go test at 6 months | in the off-medication condition | Baseline and 6 months | 
| Change from Baseline in the number of steps on the Timed Up and Go test at 12 months | in the off-medication condition | Baseline and 12 months | 
| Change from Baseline in the number of steps on the Timed Up and Go test at 6 months | in the off-medication condition | Baseline and 6 months | 
| Change from Baseline in the Movement Disorder Society-sponsord Unified Parkinson's Disease Rating Scale Part III at 6 months | In the off-medication condition, scores could range from 0 (no movement symptoms) to 72 (severe movement symptoms). | Baseline and 6 months | 
| Change from Baseline in balance confidence on the Activities-Specific Balance Confidence Scale (ABC) at 12 months | The scores could range from 0 (no balance confidence) to 100 (good balance confidence). | Baseline and 12 months | 
| Change from Baseline in balance confidence on the Activities-Specific Balance Confidence Scale (ABC) at 6 months | The scores could range from 0 (no balance confidence) to 100 (good balance confidence). | Baseline and 6 months | 
| Change from Baseline in freezing of gait on the New Freezing of Gait Questionnaire (NFOG-Q) at 12 months | The scores could range from 0 (no freezing of gait) to 28 (severe freezing of gait). | Baseline and 12 months | 
| Change from Baseline in freezing of gait on the New Freezing of Gait Questionnaire (NFOG-Q) at 6 months | The scores could range from 0 (no freezing of gait) to 28 (severe freezing of gait). | Baseline and 6 months | 
| Change from Baseline in dysphagia severity on the Swallowing Disturbance Questionnaire (SDQ) at 12 months | The scores could range from 0 (no dysphagia) to 44.5 (severe dysphagia). | Baseline and 12 months | 
| Change from Baseline in dysphagia severity on the Swallowing Disturbance Questionnaire (SDQ) at 6 months | The scores could range from 0 (no dysphagia) to 44.5 (severe dysphagia). | Baseline and 6 months | 
| Change from Baseline in gait impairment on the Gait and Fall Questionnaire (GFQ) at 12 months | The scores could range from 0 (no gait impairment) to 64 (severe gait impairment). | Baseline and 12 months | 
| Change from Baseline in gait impairment on the Gait and Fall Questionnaire (GFQ) at 6 months | The scores could range from 0 (no gait impairment) to 64 (severe gait impairment). | Baseline and 6 months | 
| Change from Baseline in medication usage on the Levodopa Equivalent Daily Dose at 12 months |  | Baseline and 12 months | 
| Change from Baseline in medication usage on the Levodopa Equivalent Daily Dose at 6 months |  | Baseline and 6 months | 
| Change from Baseline in maximal phonatory time at 12 months |  | Baseline and 12 months | 
| Change from Baseline in maximal phonatory time at 6 months |  | Baseline and 6 months | 
| Change from Baseline in dysphonia severity index (DSI) at 12 months | DSI=0.13 x MPT + 0.0053 x F-High - 0.26 x I-Low - 1.18 x Jitter (%) + 12.4. The DSI for perceptually normal voices equals +5 and for severely dysphonic voices -5. The more negative the patient's index is, the worse is his or her vocal quality. | Baseline and 12 months | 
| Change from Baseline in dysphonia severity index (DSI) at 6 months | DSI=0.13 x MPT + 0.0053 x F-High - 0.26 x I-Low - 1.18 x Jitter (%) + 12.4. The DSI for perceptually normal voices equals +5 and for severely dysphonic voices -5. The more negative the patient's index is, the worse is his or her vocal quality. | Baseline and 6 months | 
| Change from Baseline in cognition on the Montreal Cognitive Assessment at 12 months | The scores could range from 0 (severe cognition impairment) to 30 (no cognition impairment). | Baseline and 12 months | 
| Change from Baseline in cognition on the Montreal Cognitive Assessment at 6 months | The scores could range from 0 (severe cognition impairment) to 30 (no cognition impairment). | Baseline and 6 months | 
| Adverse events |  | up to 12 months after surgery | 
| Change from Baseline in balance ability on the Burg Balance Scale (BBS) at 6 months | In the off-medication condition, the scores could range from 0 (severe balance problem) to 56 (no balance problem). | Baseline and 6 months | 
| Change from Baseline in the number of freezing episodes on the Timed Up and Go test at 6 months | in the off-medication condition | Baseline and 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
postural instability/gait difficulty, deep brain stimulation, subthalamic nucleus, globus pallidus internus