Effect of Levodopa on Postural Motor Learning in Parkinson Disease

• Sponsor: VA Office of Research and Development (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT02239978
• Collaborator: Oregon Health and Science University (Other)
• Enrollment: 42
• Locations: 3
• Duration (Months): 25
• Patients Per Site: 14
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The primary goal of this project is to gain a better understanding of whether and how levodopa (a common anti-Parkinson disease medication) alters postural motor learning in people with Parkinson disease. A secondary goal is to assess whether motor cortical excitability, measured via Transcranial magnetic stimulation, is related to postural motor learning.

Participants with Parkinson disease will complete between 50 and 100 postural perturbations (via support surface translations), ON and OFF their dopamine replacement therapy (i.e. levodopa). Adaptation of responses to these perturbations will be tracked. Participants will also undergo transcranial magnetic stimulation to capture cortical excitability of the brain (in particular the motor cortex). Cortical excitability will be correlated to adaptation of stepping (i.e. postural motor learning) ON and OFF levodopa. Investigators will also capture postural motor learning and cortical excitability in age-matched healthy adults.

Investigators hypothesize that dopamine will have a negative effect on postural motor learning, and the cortical excitability will be correlated to postural motor learning.

Condition or Disease	Intervention/Treatment	Phase
Parkinson Disease	Behavioral: Postural perturbation

Study Design

• Study Type: Observational
• Actual Enrollment: 42 participants
• Observational Model: Cohort
• Time Perspective: Cross-Sectional
• Official Title: Effect of Levodopa on Postural Motor Learning in Parkinson Disease
• Study Start Date: Aug 1, 2014
• Actual Primary Completion Date: Jan 1, 2016
• Actual Study Completion Date: Sep 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Parkinsons disease Individuals with Parkinsons disease	Behavioral: Postural perturbation; Participants will undergo between 50 and 100 postural perturbations (quick movements of the support surface) in multiple directions. These perturbations will be between 9 and 24cm, and between 18 and 56 cm/s depending on participant tolerance.
Control Age-matched healthy adults	Behavioral: Postural perturbation; Participants will undergo between 50 and 100 postural perturbations (quick movements of the support surface) in multiple directions. These perturbations will be between 9 and 24cm, and between 18 and 56 cm/s depending on participant tolerance.

Outcome Measures

Primary Outcome Measures

1. Change in Movement of Center of Mass (COM) After Postural Perturbation [Baseline and follow up (24 hours later) both ON and OFF antiparkinson medication]

   Investigators will assess (via automated and custom Matlab software) the magnitude of COM movement after a postural perturbation is delivered via motion of the support surface. This will be measured throughout the intervention, as well as at follow up (24 hour later).

2. Change in Steps After Postural Perturbation [Baseline and follow up (24 hours later) both ON and OFF antiparkinson medication]

   Investigators will assess (via automated and custom Matlab software) the number of steps taken after a postural perturbation is delivered via motion of the support surface. This will be measured throughout the intervention, as well as at follow up (24 hour later).

Secondary Outcome Measures

1. Change in First Step Length [Baseline and follow up (24 hours later) both ON and OFF antiparkinson medication]

   Investigators will assess (via automated and custom Matlab software) the length of the first step after a postural perturbation is delivered via motion of the support surface. This will be measured throughout the intervention, as well as at follow up (24 hour later).

2. Cortical Excitability [TMS data was collected ON and OFF medication during one visit. This visit occurred within 3 weeks of the initial postural control assessments.]

   Investigators will assess the cortical excitability of the primary motor cortex in a subset of participants both ON and OFF levodopa. Specifically, we used transcranial magnetic stimulation to stimulate the motor cortex, where we measure muscular activity of the arm (i.e. motor evoked potentials; MEPs). The primary outcome variable noted below is the lowest stimulation setting (measured as a percentage) which results in an MEP in 5 of 10 trials.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Between 18 and 90 years of age.

• Individuals with Parkinson Disease

• Healthy adults age-matched to PD participants

• Participants with PD will be currently taking dopamine replacement (i.e. Levodopa)

Exclusion Criteria:

All subjects exclusion criteria:

• Deep brain stimulation

• Recent (within 6 months) orthopedic injuries influencing standing or balance

• Inability to stand independently

Transcranial magnetic stimulation exclusion criteria (for the subset of individuals taking part in the Transcranial Magnetic Stimulation portion of the study):

• History of epilepsy or currently taking any epileptic medication,

• History of seizures

• Family history of epilepsy or seizures

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Oregon Health & Science University	Portland	Oregon	United States	97210
2	VA Portland Health Care System, Portland, OR	Portland	Oregon	United States	97239
3	VA Salt Lake City Health Care System, Salt Lake City, UT	Salt Lake City	Utah	United States	84148

Sponsors and Collaborators

• VA Office of Research and Development
• Oregon Health and Science University

Investigators

• Principal Investigator: Daniel S Peterson, PhD MS BS, VA Salt Lake City Health Care System, Salt Lake City, UT

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT02239978
• Other Study ID Numbers: N1480-M
• First Posted: Sep 15, 2014
• Last Update Posted: Feb 23, 2017
• Last Verified: Jan 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by VA Office of Research and Development: Parkinson Disease; Posture Balance; Learning; Dopamine
• Additional relevant MeSH terms: Parkinson Disease

Study Results

Participant Flow

Recruitment Details	A total of 42 individuals were enrolled in the study (30 people with Parkinson's disease and 12 healthy older adults)

Arm/Group Title	Parkinsons Disease	Control
Arm/Group Description	Individuals with Parkinsons disease Postural perturbation: Participants will undergo between 50 and 100 postural perturbations (quick movements of the support surface) in multiple directions. These perturbations will be between 9 and 24cm, and between 18 and 56 cm/s depending on participant tolerance.	Age-matched healthy adults Postural perturbation: Participants will undergo between 50 and 100 postural perturbations (quick movements of the support surface) in multiple directions. These perturbations will be between 9 and 24cm, and between 18 and 56 cm/s depending on participant tolerance.
Period Title: Overall Study
STARTED	30	12
COMPLETED	28	12
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	Parkinsons Disease	Control	Total
Arm/Group Description	Individuals with Parkinsons disease Postural perturbation: Participants will undergo between 50 and 100 postural perturbations (quick movements of the support surface) in multiple directions. These perturbations will be between 9 and 24cm, and between 18 and 56 cm/s depending on participant tolerance.	Age-matched healthy adults Postural perturbation: Participants will undergo between 50 and 100 postural perturbations (quick movements of the support surface) in multiple directions. These perturbations will be between 9 and 24cm, and between 18 and 56 cm/s depending on participant tolerance.	Total of all reporting groups
Overall Participants	30	12	42
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	11 36.7%	3 25%	14 33.3%
>=65 years	19 63.3%	9 75%	28 66.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.05 (9.67)	68.04 (6.62)	67.16 (7.10)
Gender (Count of Participants)
Female	10 33.3%	6 50%	16 38.1%
Male	20 66.7%	6 50%	26 61.9%
Region of Enrollment (participants) [Number]
United States	30 100%	12 100%	42 100%

Outcome Measures

1. Primary Outcome

Title	Change in Movement of Center of Mass (COM) After Postural Perturbation
Description	Investigators will assess (via automated and custom Matlab software) the magnitude of COM movement after a postural perturbation is delivered via motion of the support surface. This will be measured throughout the intervention, as well as at follow up (24 hour later).
Time Frame	Baseline and follow up (24 hours later) both ON and OFF antiparkinson medication

Outcome Measure Data

Analysis Population Description

We were unable to collect reliable data on some of the people with PD while OFF medication, which is why there is a discrepancy between the "Parkinson's disease" and "Parkinson's disease Off Medication" arms.

Arm/Group Title	Parkinsons Disease	Control	Parkinson's Disease Off Medication
Arm/Group Description	Individuals with Parkinsons disease Postural perturbation: Participants will undergo between 50 and 100 postural perturbations (quick movements of the support surface) in multiple directions. These perturbations will be between 9 and 24cm, and between 18 and 56 cm/s depending on participant tolerance.	Age-matched healthy adults Postural perturbation: Participants will undergo between 50 and 100 postural perturbations (quick movements of the support surface) in multiple directions. These perturbations will be between 9 and 24cm, and between 18 and 56 cm/s depending on participant tolerance.	These are the same individuals in the "Parkinson's disease" group, but Off their levodopa
Measure Participants	28	12	24
Start Train	0.31 (0.11)	0.28 (0.05)	0.32 (0.13)
End Train	0.26 (0.10)	0.23 (0.03)	0.31 (0.12)

2. Primary Outcome

Title	Change in Steps After Postural Perturbation
Description	Investigators will assess (via automated and custom Matlab software) the number of steps taken after a postural perturbation is delivered via motion of the support surface. This will be measured throughout the intervention, as well as at follow up (24 hour later).
Time Frame	Baseline and follow up (24 hours later) both ON and OFF antiparkinson medication

Outcome Measure Data

Analysis Population Description

We were unable to collect reliable data on some of the people with PD while OFF medication, which is why there is a discrepancy between the "Parkinson's disease" and "Parkinson's disease Off Medication" arms.

Arm/Group Title	Parkinsons Disease	Control	Parkinson's Disease Off Medication
Arm/Group Description	Individuals with Parkinsons disease Postural perturbation: Participants will undergo between 50 and 100 postural perturbations (quick movements of the support surface) in multiple directions. These perturbations will be between 9 and 24cm, and between 18 and 56 cm/s depending on participant tolerance.	Age-matched healthy adults Postural perturbation: Participants will undergo between 50 and 100 postural perturbations (quick movements of the support surface) in multiple directions. These perturbations will be between 9 and 24cm, and between 18 and 56 cm/s depending on participant tolerance.	These are the same individuals in the "Parkinson's disease" group, but Off their levodopa
Measure Participants	28	12	24
Start Train	2.22 (0.9)	2.03 (0.63)	2.09 (0.77)
End Train	1.92 (1.15)	1.15 (0.28)	2.05 (1.12)

3. Secondary Outcome

Title	Change in First Step Length
Description	Investigators will assess (via automated and custom Matlab software) the length of the first step after a postural perturbation is delivered via motion of the support surface. This will be measured throughout the intervention, as well as at follow up (24 hour later).
Time Frame	Baseline and follow up (24 hours later) both ON and OFF antiparkinson medication

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Parkinsons Disease	Control	Parkinson's Disease Off Medication
Arm/Group Description	Individuals with Parkinsons disease Postural perturbation: Participants will undergo between 50 and 100 postural perturbations (quick movements of the support surface) in multiple directions. These perturbations will be between 9 and 24cm, and between 18 and 56 cm/s depending on participant tolerance.	Age-matched healthy adults Postural perturbation: Participants will undergo between 50 and 100 postural perturbations (quick movements of the support surface) in multiple directions. These perturbations will be between 9 and 24cm, and between 18 and 56 cm/s depending on participant tolerance.	These are the same individuals in the "Parkinson's disease" group, but Off their levodopa
Measure Participants	28	12	24
Start of Training	0.18 (0.06)	0.25 (0.11)	0.21 (0.08)
End of Training	0.20 (0.08)	0.27 (0.08)	0.21 (0.08)

4. Secondary Outcome

Title	Cortical Excitability
Description	Investigators will assess the cortical excitability of the primary motor cortex in a subset of participants both ON and OFF levodopa. Specifically, we used transcranial magnetic stimulation to stimulate the motor cortex, where we measure muscular activity of the arm (i.e. motor evoked potentials; MEPs). The primary outcome variable noted below is the lowest stimulation setting (measured as a percentage) which results in an MEP in 5 of 10 trials.
Time Frame	TMS data was collected ON and OFF medication during one visit. This visit occurred within 3 weeks of the initial postural control assessments.

Outcome Measure Data

Analysis Population Description

As noted in our protocol, TMS was assessed in a subgroup of participants with PD. Seven of the 28 PD participants and 0 of the "control" group (healthy adults) were assessed. PD participants were assessed ON and OFF levodopa. We chose this approach because 1) this aim was exploratory in nature, and 2) MEPs of healthy adults are well characterized.

Arm/Group Title	Parkinsons Disease	Parkinson's Disease Off Medication
Arm/Group Description	Individuals with Parkinsons disease Postural perturbation: Participants will undergo between 50 and 100 postural perturbations (quick movements of the support surface) in multiple directions. These perturbations will be between 9 and 24cm, and between 18 and 56 cm/s depending on participant tolerance.	These are the same participants as in the Parkinson's disease group, assessed "Off" their levodopa medication
Measure Participants	7	7
Mean (Standard Deviation) [% max stim output]	40.57 (8.73)	40.71 (9.97)

Adverse Events

Arm/Group Title	Parkinsons Disease		Control
Arm/Group Description	Individuals with Parkinsons disease Postural perturbation: Participants will undergo between 50 and 100 postural perturbations (quick movements of the support surface) in multiple directions. These perturbations will be between 9 and 24cm, and between 18 and 56 cm/s depending on participant tolerance.		Age-matched healthy adults Postural perturbation: Participants will undergo between 50 and 100 postural perturbations (quick movements of the support surface) in multiple directions. These perturbations will be between 9 and 24cm, and between 18 and 56 cm/s depending on participant tolerance.
All Cause Mortality
	Parkinsons Disease		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Parkinsons Disease		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Parkinsons Disease		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.