Physical Therapy and Deep Brain Stimulation in Parkinson Disease (PTDBS)

• ClinicalTrials.gov Identifier: NCT03181282
• Recruitment Status: Completed
• First Posted: June 8, 2017
• Results First Posted: March 22, 2023
• Last Update Posted: March 22, 2023
• Sponsor: Washington University School of Medicine
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): Ryan Duncan, Washington University School of Medicine

Study Description

Brief Summary:

While deep brain stimulation of the subthalamic nucleus (STN-DBS) is commonly used to reduce tremor, muscle stiffness, and bradykinesia in people with Parkinson disease (PD), preliminary studies suggest balance may worsen and falls may increase after STN-DBS. Walking speed, known to be reduced in PD, typically improves after surgery; however, other important gait qualities may not improve. Given the potential for worsening balance and gait and increasing falls after surgery, it is imperative that researchers explore interventions that complement the positive effects of STN-DBS and delay worsening of balance and gait.

Physical therapy (PT) is reported to be effective in improving balance and walking in people with PD. However, there have been no studies to investigate how individuals with STN-DBS respond to PT. As such, it is unclear if exercise in the post-DBS population is safe, feasible, and effective. The purpose of this study is to examine the safety, feasibility, and efficacy of PT in people with PD with STN-DBS.

The investigators hypothesize that PT will be safe and feasible for people with PD with STN-DBS. Further, the investigators hypothesize that those assigned to PT group will demonstrate improvements in balance and gait while those assigned to the control group will demonstrate no change or a decline in balance and gait.

Condition or disease	Intervention/treatment	Phase
Parkinson Disease	Behavioral: Physical Therapy	Not Applicable

Detailed Description:

Deficits in balance and gait may lead to falls, fall-related complications, and physical inactivity in people with PD. These negative effects are thought to lead to a 'malignant' form of PD in which there is reduced quality of life and increased risk for mortality. While people who have had STN-DBS often experience reductions in tremor, rigidity, and bradykinesia, surgical management of PD may not be effective in ameliorating impairments in balance and gait. In fact, investigators have reported that DBS may worsen balance, which may accelerate an individual's decline toward 'malignant' PD. To this end, recent studies indicate physical activity levels did not increase after STN-DBS. This finding should not go unnoticed as physical activity may have a disease modifying effect, slowing the progression of motor disability. As of 2011, approximately 70,000 people with PD have undergone DBS, with the annual number of DBS procedures for PD totaling between 8,000-10,000. In addition, investigators are now studying the effects of STN-DBS in people with early PD. The procedure appears to be safe and effective in this population, which will increase the number of surgical candidates. With the number of people with PD expected to double to more than 8 million by 2030, the number of those receiving DBS is expected to substantially increase.

Given the expected rise in STN-DBS procedures and potential for worsening of postural instability and gait deficits, there is a clear need for interventions that prevent these negative complications of STN-DBS.

Physical therapy, delivered using various treatment approaches (e.g. treadmill training, balance training), is effective in reducing postural instability and improving spatiotemporal gait characteristics among individuals with PD who do not have DBS. To our knowledge, there are no studies to date that assessed the impact of PT for those with PD who have DBS. In fact, the current standard of care following STN-DBS does not include PT. Current care post-DBS includes pharmacologic management and monitoring of DBS settings, which are optimized based on Unified Parkinson's Disease Rating Scale motor subsection (UPDRS III) scores. Despite the introduction of substantial changes to neural activity in areas of the brain governing movement with DBS, formal movement training or assessment of functional mobility and safety are not provided after surgery. As such, patients may not experience significant improvements in postural stability and gait following surgery, and may be at increased risk for falls, fall-related complications, and development of a sedentary lifestyle. Physical therapy is a personalized intervention that can be used to address specific movement impairments that remain even when patients are on optimal regimens of medication and DBS. There is an urgent need to determine if PT is effective in improving postural stability and gait performance over time following STN-DBS. If the intervention is safe and feasible, future studies could evaluate the efficacy of PT for gait and balance deficits in this population before and/or immediately post-surgery, increasing the potential impact of this research.

In this pilot randomized controlled trial, participants will be randomly assigned to either the physical therapy group or control group. Those in the physical therapy group will attend 1-hour sessions of PT twice weekly with a treatment plan designed to improve balance and gait. Those in the control group will not be prescribed an exercise intervention.

Each participant will undergo the same battery of balance and gait tests. Although STN-DBS settings are typically stable at 12 months post-surgery, participants will be allowed to follow up with their neurologists as needed for programming and medication adjustments. All changes in programming settings and medication dosages will be noted. A rater, blinded to group assignment, will collect all outcomes at each time point. Participants will be tested in the following conditions: 1) OFF stimulation and OFF medication and 2) ON stimulation and ON medication. Testing participants OFF stimulation/OFF medication will allow us to determine if the addition of PT after STN-DBS affects balance and gait independent of other treatments. OFF medication is defined as greater than or equal to 12 hours since the last intake of anti-PD medication. For OFF stimulation/OFF medication testing, participants will arrive to the laboratory OFF medication but with stimulators on. The stimulators will be turned OFF upon arrival at the laboratory and testing will commence 45 minutes after the stimulators are turned OFF. Stimulators will be turned back on upon completion of this testing session. The investigators anticipate the total time for this laboratory visit to be 2 hours. Testing ON stimulation/ON medication will provide insight into how participants perform on an everyday basis. ON medication is defined as 1-1.5 hours after medication intake. For ON stimulation/ON medication assessments, participants will arrive to the laboratory 1-1.5 hours after taking their normal anti-PD medication dose with stimulators on and stimulators will remain on throughout the session. Assessments will occur at baseline and at 8 (i.e. post-test) and 12 weeks (i.e. follow up). Assessments will take place on two separate days and the order of testing condition (OFF medication/OFF stimulation vs. ON medication/ON stimulation) will be randomized. The Movement Disorders Society-Unified Parkinson Disease Rating Scale III (MDS-UPDRS III) will be administered in each condition.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Masking Description: Outcomes assessor will be blinded to group assignment.
• Primary Purpose: Treatment
• Official Title: Physical Therapy and Deep Brain Stimulation in Parkinson Disease
• Actual Study Start Date: August 3, 2017
• Actual Primary Completion Date: August 2, 2019
• Actual Study Completion Date: August 2, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Physical Therapy; Participants assigned to Physical Therapy (PT) will attend a 1-hour visit with a physical therapist twice weekly for 8 weeks. The PT intervention, which will mirror traditional PT for those with PD, will include exercises designed to improve balance and gait.	Behavioral: Physical Therapy; Postural stability exercises will follow a framework targeting quiet stance, anticipatory and reactive postural adjustments, and dynamic postural control. Gait exercises will include treadmill walking and practice with dual-task gait. A home exercise program (HEP), to be completed twice weekly, will be provided on each participant's initial visit with the physical therapist following STN-DBS surgery. The HEP will include the following exercises: trunk rotation, standing hip flexion, standing hip abduction, standing plantarflexion, and standing squat.; Other Name: Physical Rehabilitation
No Intervention: Control; Participants in the control group will receive the current standard of care following STN-DBS. As such, STN-DBS settings and anti-PD medications will be optimized according to the determination of their neurologist in the same fashion as they will be in the experimental group. Those in the control group will not receive prescribed exercise from a physical therapist.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Treatment-Emergent Adverse Events [Safety & Tolerability] [ Time Frame: 8 weeks ]
   Number of participants with falls, orthopedic injuries, or other adverse events that are related to treatment.

Secondary Outcome Measures :

1. Treatment-Related Adherence [Feasibility] [ Time Frame: 8 weeks ]
   Feasibility of the treatment as measured by the number of PT sessions attended.
2. Balance [ Time Frame: 8 weeks ]

   Change in Balance Evaluation Systems Test score. The scale is scored from 0-100% with higher scores indicating better balance. Here, the higher the change score, the greater the improvement in balance.

   A change score of 0.04 would correspond to a 4% improvement in the BESTest score. A change score of -0.02 would correspond to a 2% decline in BESTest score.

3. Gait [ Time Frame: 8 weeks ]
   Change in gait velocity (cm/sec). Higher gait speeds are associated with better mobility. The greater the value for the change in gait speed, the greater the improvement in gait speed. Negative values would indicate a decline in gait speed.

Eligibility Criteria

• Ages Eligible for Study: 30 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Diagnosis of idiopathic Parkinson disease
• Hoehn & Yahr stages II-IV
• At least 1 year post-STN-DBS
• Able to provide informed consent

Exclusion Criteria:

• Diagnosis of atypical parkinsonism
• Hoehn & Yahr stages I or V
• Evidence of dementia (MMSE < 24/30)
• Inability to walk 10 meters with or without assistive device

Contacts and Locations

Locations

United States, Missouri

Washington University in St. Louis School of Medicine - Program in Physical Therapy

Saint Louis, Missouri, United States, 63108

Sponsors and Collaborators

Washington University School of Medicine

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: Ryan P Duncan, DPT; Washington University in St. Louis School of Medicine - Program in Physical Therapy

  Study Documents (Full-Text)

Documents provided by Ryan Duncan, Washington University School of Medicine:

Study Protocol and Statistical Analysis Plan  [PDF] May 11, 2017

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Duncan RP, Van Dillen LR, Garbutt JM, Earhart GM, Perlmutter JS. Physical therapy and deep brain stimulation in Parkinson's Disease: protocol for a pilot randomized controlled trial. Pilot Feasibility Stud. 2018 Feb 21;4:54. doi: 10.1186/s40814-018-0243-2. eCollection 2018.

• Responsible Party: Ryan Duncan, Assistant Professor of Physical Therapy, Assistant Professor of Neurology, Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT03181282
• Other Study ID Numbers: 201609148; K12HD055931 ( U.S. NIH Grant/Contract )
• First Posted: June 8, 2017
• Results First Posted: March 22, 2023
• Last Update Posted: March 22, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ryan Duncan, Washington University School of Medicine:

Deep brain stimulation; Balance; Gait; Physical Therapy; Parkinson disease

Additional relevant MeSH terms:

Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases