Deep Brain Stimulation Effects on Gait and Balance in Patients With Parkinson's Disease
Phase: NA
Conditions: Parkinson's Disease
Sponsor: University of Miami

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PROTOCOL 
 
Official Title: Deep brain stimulation effects on gait and balance in patients with 
Parkinson's disease 
 
PI: Corneliu Luca MD, PhD 
 
Document Date: January 4, 2016 
 
NCT Number: NCT02022735 
 
 
1. STUDY DESIGN AND SCHEMA:  
 
Gait and balance problems are dopamine resistant features of Parkinson’s disease (PD). 
Deep brain stimulation of sub-thalamic nucleus (STN–DBS) is an established surgical 
method that improves motor symptoms and gait in PD, however it may produce 
unexpected freezing of gait and balance problems in some patients, presumably due to 
overstimulation and gait incoordination.  The aim of this study is to identify the 
differential effects of unilateral STN stimulation versus bilateral stimulation on gait 
kinematics in patients with PD and associated gait dysfunction.  
2. BACKGROUND AND RATIONALE :    
 
Freezing of gait (FOG) and walking difficulties represent perhaps the most difficult 
challenges in the treatment of Parkinson’s disease (PD).  PD patients experience frequent 
difficulty initiating walking, shuffling and postural instability (Vu, Nutt et al. 2012). In 
spite of dopaminergic therapy, walking difficulties continue to progress and only rarely 
do non-dopaminergic treatments provide benefit.  Deep brain stimulation of sub-thalamic 
nucleus (STN-DBS) improves motor scores, walking and FOG  (St George, Nutt et al. 
2010). In some patients, even after appropriate fine tuning of programming, walking and 
balance continue to be a problem. One explanation can be the progression of the disease, 
however in some cases the FOG appears soon after the DBS. This has been attributed to 
overstimulation and perhaps asymmetric stimulation in the networks involved in gait 

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control. Several studies have looked at the parameters of stimulation and have concluded 
that reducing the frequency of stimulation would ameliorate walking difficulties  (Fasano, 
Herzog et al. 2011).  Similarly, reducing the amplitude contralateral to the most affected 
side is associated with less FOG  (Moreau, Defebvre et al. 2008). 
A growing body of literature suggests that right-hemisphere circuitry seems to be more 
affected than the left in patients with FOG  (Fling, Cohen et al. 2013)  and  that patients 
with worse symptoms on the left are more likely to develop postural instability gait 
dysfunction (PIGD)  (Giladi, McDermott et al. 2001) 
3. OBJECTIVES 
In this study we aim to evaluate the effects of differential STN stimulation on walking. 
We hypothesize that in patients with FOG, unilateral stimulation on the most affected 
hemisphere will ameliorate walking in a higher degree than bilateral stimulation. 
Functional asymmetry of STN was shown before by other studies  (Castrioto, Meaney et 
al. 2011) and is thought that unilateral STN stimulation has effects that are similar with 
bilateral STN on UPDRS motor scores, effect called dominant STN.  Since the effects of 
unilateral stimulation on walking are not completely understood, we plan to determine if 
unilateral stimulation has differential effects on gait kinematics. 
4.  STUDY POPULATION 
 
Inclusion criteria are: patients with idiopathic PD  with Hoehn and Yahr Stage 1-3 that 
have undergone STN-DBS and had developed difficulty walking 6-12 months after the 
DBS on stable dosage dopamine agonist/levodopa, expected to remain on the same 
dosage of treatment for the next 3 months; age 45-70. 

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Exclusion criteria are: past medical history of seizures, renal insufficiency and history of 
cardiac arrhythmia, previous DBS, severe arthritis, women of childbearing potential, 
dementia and less than 45 and over 70 years old. 
 
 
5. MEASUREMENTS AND EVALUATION  
 
This study is meant to see if there is improvement in gait or freezing of gait after changes in 
the stimulation parameters.   
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In the first part of the study subjects (1 visit) will be randomly assigned to four different 
stimulation parameters: both stimulators ON, both stimulators off, right stimulator ON, 
left stimulator ON. We will assess participants’ gait using clinical scales as well as 
wearable sensors attached to the body. Assessments will be done one hour after each 
change in the stimulation parameters.  
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In the second part of the study that participants may be asked to participate in, changes in 
the frequency of stimulation and contact stimulation will be performed.  Four different 
stimulation settings will be tested. In this part evaluations will be done.  
 
PART 1 
Screening: At this visit, the study investigator will discuss the details of the research study and 
the consent form with the study participant.   
The following procedures will also be completed: 
• 
Sign informed consent form. 
• 
Collection of a complete medical history and a neurological exam. 
• 
United Parkinson’s disease rating scale (UPDRS) will be performed by a Movement 
Disorder Specialist to assess the severity of Parkinson’s disease.  

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• 
Timed Up and Go test (TUG) - a mobility test that is used to measure the basic mobility 
skills of people who are elderly or have neurological conditions such as PD and it includes 
a sit-to-stand component as well as walking 3m, turning and returning to the chair.   
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Freezing of Gait Questionnaire (FOGQ) which is a self-report questionnaire consisting of 
16 items regarding falls and walking problems.  
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Gait analysis using wearable sensors (Mobility Lab) to measure the walking speed and 
step length. 
If study subjects meet the eligibility criteria, they will be asked to sign the informed consent 
and asked to come to clinic for part 1 or for part 2 of the study without taking their 
Parkinson’s medication for 12 hours. 
Visit 1 Changes to the DBS stimulator will be done every 60 minutes for 4 hours in a random 
order. 
• 
Bilateral stimulators ON, bilateral stimulators OFF, Right ON-Left OFF, Right OFF-Left 
ON. 
• 
UPDRS scale  
• 
Gait analysis using wearable sensors (Mobility Lab) to measure the walking speed and 
step length. 
This visit will take about 5 hours. At the end of the visit study participants will go home with 
their initial settings. 
 
PART 2 
Screening: At this visit, the study investigator will discuss the details of the research study.  
The following procedures will be completed: 
• 
United Parkinson’s disease rating scale (UPDRS) will be performed by a Movement 
Disorder Specialist to assess the severity of their Parkinson’s disease.  

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• 
Timed Up and Go test (TUG) - a mobility test that is used to measure the basic mobility 
skills of people who are elderly or have neurological conditions such as PD that includes a 
sit-to-stand component as well as walking 3m, turning and returning to the chair.   
• 
Freezing of Gait Questionnaire (FOGQ) which is a self-report questionnaire consisting of 
16 items regarding falls and walking problems.  
• 
Gait analysis using wearable sensors (Mobility Lab) to measure the walking speed and 
step length. 
• 
The PI will review the medical records to assess if precise localization of the electrode 
contacts can be done using the CT scan that was performed post-operatively and will decide 
if an MRI of the brain is necessary to perform. 
Visits 1, 2, 3 and 4  
During these visits the stimulation settings will be changed to one of the following 
conditions: Low frequency stimulation-dorsal STN, Low frequency stimulation- ventral STN, 
High frequency stimulation- dorsal STN, High frequency stimulation –ventral STN 
After each change the following tests will be performed: 
• 
United Parkinson’s disease rating scale (UPDRS) will be performed by a Movement 
Disorder Specialist to assess the severity of Parkinson’s disease.  
• 
Timed Up and go test (TUG) - a mobility test that is used to measure the basic mobility 
skills of people who are elderly or have neurological conditions such as PD and it includes 
a sit-to-stand component as well as walking 3m, turning and returning to the chair.   
• 
Freezing of Gait Questionnaire (FOGQ) which is a self-report questionnaire consisting of 
16 items regarding falls and walking problems. 
• 
Gait analysis using wearable sensors (Mobility Lab) to measure the walking speed and 
step length. 
• 
Clinical Global Improvement Scale 

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6. ASSESSMENT AND REPORTING OF ADVERSE EVENTS 
 
Patients will be monitored in the office for three hours to assess for any side effects, which 
may include worsening tremors, voice changing or worsening rigidity.   
Serious Adverse Events (SAE): Adverse Events will be monitored and logged and 
reported to the IRB. 
 
7. STATISTICAL ANALYSIS   
 
For the data analysis, we will estimate frequencies of adverse events, central tendency and 
variability for patient’s demographic characteristics, velocity, stride length, TUG and the 
UPDRS score. All analyses will be conducted using SAS (version 9.2, SAS Institute Inc., Cary, 
NC).  
 
 
8. ADHERENCE TO ETHICAL, REGULATORY AND ADMINISTRATIVE 
CONSIDERATIONS  
 
Written IRB approval will be obtained from the University of Miami Institutional Review Board 
(IRB) and from each IRB with jurisdiction over the participating Nodes as well as the individual 
CTPs when indicated.  Approval will be obtained for all aspects of the study, including the 
assessment of the risk/benefit ratio, informed consent process and document, procedures and 
rating instruments, randomization, clinical services, and videotaping.  Informed consent will also 
be obtained from the therapists to permit analyses of data by therapist characteristics and 
therapy process. Any changes that impact the risk/benefit ratio of the study as well as changes to 
the protocol or to the consent process will be submitted and approved by each IRB prior to 
implementation. No advertising or direct soliciting of participants will be initiated without IRB 
approval of all written flyers/brochures/ documents. 
 
9. 
REFERENCES  
 
(1) Vu TC, Nutt JG, Holford NHG. Progression of motor and nonmotor features of parkinson's 
disease and their response to treatment. Br J Clin Pharmacol. 2012;74(2):267-83.  
(2). St George RJ, Nutt JG, Burchiel KJ, et al. A meta-regression of the long-term effects of 
deep brain stimulation on balance and gait in PD. Neurology. 2010 Oct 5;75(14):1292-9.  

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(3). Fasano A, Herzog J, Seifert E, et al. Modulation of gait coordination by subthalamic 
stimulation improves freezing of gait. Mov Disord. 2011 Apr;26(5):844-51.  
(4). Moreau C, Defebvre L, Destee A, et al. STN-DBS frequency effects on freezing of gait in 
advanced parkinson disease. Neurology. 2008 Jul 8;71(2):80-4.  
(5). Fling BW, Cohen RG, Mancini M, et al. Asymmetric pedunculopontine network 
connectivity in parkinsonian patients with freezing of gait. Brain. 2013 Aug;136(Pt 8):2405-
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(6). Giladi N, McDermott MP, Fahn S, et al. Freezing of gait in PD: Prospective assessment in 
the DATATOP cohort. Neurology. 2001 Jun 26;56(12):1712-21.  
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(9). Moreau C, Defebvre L, Destee A, et al. STN-DBS frequency effects on freezing of gait in 
advanced parkinson disease. Neurology. 2008 Jul 8;71(2):80-4.  
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