Clinical trial NCT03181282: Physical Therapy and Deep Brain Stimulation in Parkinson Disease
Official title: Physical Therapy and Deep Brain Stimulation in Parkinson Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Parkinson Disease
Keywords: Deep brain stimulation
Balance
Gait
Physical Therapy
Parkinson disease
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2017-06-08
Enrollment: 31
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events [Safety & Tolerability]
timeFrame: 8 weeks
Secondary outcomes:
measure: Treatment-Related Adherence [Feasibility]
timeFrame: 8 weeks
measure: Balance
timeFrame: 8 weeks
measure: Gait
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University in St. Louis School of Medicine - Program in Physical Therapy
state: Missouri
Study officials:
affiliation: Washington University in St. Louis School of Medicine - Program in Physical Therapy
name: Ryan P Duncan, DPT
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.