Genetic Influences on Response to Gait Rehabilitation in Parkinson's Disease
| Status: | Recruiting |
|---|---|
| Conditions: | Parkinsons Disease |
| Therapuetic Areas: | Neurology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 1/2/2019 |
| Start Date: | February 1, 2018 |
| End Date: | March 31, 2020 |
| Contact: | James Phillips, BS |
| Email: | James.Phillips663@va.gov |
| Phone: | (206) 627-6139 |
Genetic Influences on Response to Gait Rehabilitation in Parkinson?s Disease
The aging Veteran population, together with high exposure to Agent Orange or other herbicides
during military service, has made diseases such as Parkinson's disease (PD), currently
affecting more than 80,000 Veterans, a major health issue in the Veterans' health system.
Mobility and cognitive limitations are a common problem in PD and are associated with
significant disability, increased fall risk, reduced quality of life, and increased caregiver
burden. While less is known about its benefit on cognition, physical therapy has proven to be
an effective treatment to mitigate mobility limitations, though the response to
rehabilitation interventions is highly variable. The proposed research will inform the
investigators' understanding of the impact of certain genetic profiles associated with
learning impairments on motor and cognitive benefits in response to gait rehabilitation, and
will provide an important foundation for more personalized and improved gait rehabilitation
programs for different subgroups of PD patients.
during military service, has made diseases such as Parkinson's disease (PD), currently
affecting more than 80,000 Veterans, a major health issue in the Veterans' health system.
Mobility and cognitive limitations are a common problem in PD and are associated with
significant disability, increased fall risk, reduced quality of life, and increased caregiver
burden. While less is known about its benefit on cognition, physical therapy has proven to be
an effective treatment to mitigate mobility limitations, though the response to
rehabilitation interventions is highly variable. The proposed research will inform the
investigators' understanding of the impact of certain genetic profiles associated with
learning impairments on motor and cognitive benefits in response to gait rehabilitation, and
will provide an important foundation for more personalized and improved gait rehabilitation
programs for different subgroups of PD patients.
The completion of the Human Genome Project in 2003 marked the beginning of the genomic era
and the birth of "personalized" (precision) medicine. In the last decade, genetics have
provided a new understanding of predicting, diagnosing, and treating individual health
conditions. Indeed, such precision medicine has begun to impact virtually all areas of
medicine, with significant potential to influence the timing, dosage, and intensity of
physical rehabilitation.
The long-term goals of this research are: (1) to determine if certain genetic variants
associated to learning impairments impact the motor and cognitive benefit experienced in
response to physical rehabilitation in Veterans with Parkinson's disease (PD), and (2) to use
that knowledge to identify subpopulations of patients that may require rehabilitative
strategies tailored to their genotype to optimize physical rehabilitation. To achieve these
goals the investigators will enroll 30 Veterans with PD in a 10-week moderate intensity gait
training program consisting of 2 times per week treadmill training with verbal cues for gait
quality. Aim 1 will examine the association between variants in 2 genes known to affect
cognition and motor learning (APOE- 4 and BDNF-Met66), and motor improvements after gait
training. Specifically, changes in walking from during and after training will be sensitively
and objectively assessed using state-of-the-art quantitative gait analysis, and compared
between three genotype groups (carriers of BDNF-Met66 (N=10), carriers of APOE- 4 (N=10) and
those not carrying either of those variants (N=10)). Aim 2 will examine the effect of APOE- 4
and BDNF-Met66 genetic variants on cognitive changes in response to this training program. In
order to do this the investigators will measure cognitive performance pre- and post-training
using a brief, targeted battery aimed at assessing attention, processing speed, executive
function, and learning/memory, the domains more affected, and more likely to improve with
physical exercise in PD. The investigators will test the hypothesis that Veterans with PD who
carry an APOE- 4 or BDNF-Met66 allele will demonstrate smaller improvements in gait (Aim 1)
and cognition (Aim 2) in response to a 10-week gait training program. Overall the results of
this project will enhance the investigators' knowledge regarding the influence of different
genetic profiles in the response to physical rehabilitation in Veterans with PD, and will
generate supporting data that will translate to more personalized and effective
rehabilitation programs for people with PD.
and the birth of "personalized" (precision) medicine. In the last decade, genetics have
provided a new understanding of predicting, diagnosing, and treating individual health
conditions. Indeed, such precision medicine has begun to impact virtually all areas of
medicine, with significant potential to influence the timing, dosage, and intensity of
physical rehabilitation.
The long-term goals of this research are: (1) to determine if certain genetic variants
associated to learning impairments impact the motor and cognitive benefit experienced in
response to physical rehabilitation in Veterans with Parkinson's disease (PD), and (2) to use
that knowledge to identify subpopulations of patients that may require rehabilitative
strategies tailored to their genotype to optimize physical rehabilitation. To achieve these
goals the investigators will enroll 30 Veterans with PD in a 10-week moderate intensity gait
training program consisting of 2 times per week treadmill training with verbal cues for gait
quality. Aim 1 will examine the association between variants in 2 genes known to affect
cognition and motor learning (APOE- 4 and BDNF-Met66), and motor improvements after gait
training. Specifically, changes in walking from during and after training will be sensitively
and objectively assessed using state-of-the-art quantitative gait analysis, and compared
between three genotype groups (carriers of BDNF-Met66 (N=10), carriers of APOE- 4 (N=10) and
those not carrying either of those variants (N=10)). Aim 2 will examine the effect of APOE- 4
and BDNF-Met66 genetic variants on cognitive changes in response to this training program. In
order to do this the investigators will measure cognitive performance pre- and post-training
using a brief, targeted battery aimed at assessing attention, processing speed, executive
function, and learning/memory, the domains more affected, and more likely to improve with
physical exercise in PD. The investigators will test the hypothesis that Veterans with PD who
carry an APOE- 4 or BDNF-Met66 allele will demonstrate smaller improvements in gait (Aim 1)
and cognition (Aim 2) in response to a 10-week gait training program. Overall the results of
this project will enhance the investigators' knowledge regarding the influence of different
genetic profiles in the response to physical rehabilitation in Veterans with PD, and will
generate supporting data that will translate to more personalized and effective
rehabilitation programs for people with PD.
Inclusion Criteria:
- Meet UK Brain Bank (UKBB) criteria for the diagnosis of PD (modified so that having
more than one affected relative was not considered an exclusion criteria)
- Have a Hoehn & Yahr score of 3
- Have the ability to walk 400 m without physical assistance from a device or another
person
- Do not have other health conditions (e.g., orthopedic, cardiopulmonary) that impact
the ability to safely participate in a moderately intense gait training program
Exclusion Criteria:
- The investigators will exclude those patients presenting clinical diagnosis of
dementia.
We found this trial at
1
site
Seattle, Washington 98108
Principal Investigator: Ignacio Fernandez-Mata
Phone: 206-627-6167
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