Exercise and Cognitive Training in Parkinson's Disease

• ClinicalTrials.gov Identifier: NCT01156714
• Recruitment Status: Completed
• First Posted: July 5, 2010
• Results First Posted: March 5, 2019
• Last Update Posted: March 5, 2019
• Sponsor: VA Office of Research and Development
• Collaborator: University of Maryland
• Information provided by (Responsible Party): VA Office of Research and Development

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Parkinson's Disease
• Interventions: Behavioral: Treadmill training with aerobic exercise; Behavioral: Memory training with computerized memory program; Behavioral: Combination of treadmill training and computerized memory
• Enrollment: 59

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Arm 1: Treadmill Training	Arm 2: Memory Training	Arm 3: Treadmill and Memory Training
Arm/Group Description	Treadmill training with aerobic exercise treadmill training: walk on treadmill for aerobic exercise	Memory training with computerized memory program computerized memory training: memory testing and training on computer program	Combination of treadmill training and computerized memory program treadmill training: walk on treadmill for aerobic exercise computerized memory training: memory testing and training on computer program
Period Title: Overall Study
Started	20	19	20
Completed	11	15	17
Not Completed	9	4	3
Reason Not Completed
Withdrawal by Subject	9	4	3

Baseline Characteristics

Arm/Group Title		Arm 1: Treadmill Training	Arm 2: Memory Training	Arm 3: Treadmill and Memory Training	Total
Arm/Group Description		Treadmill training with aerobic exercise treadmill training: walk on treadmill for aerobic exercise	Memory training with computerized memory program computerized memory training: memory testing and training on computer program	Combination of treadmill training and computerized memory program treadmill training: walk on treadmill for aerobic exercise computerized memory training: memory testing and training on computer program	Total of all reporting groups
Overall Number of Baseline Participants		20	19	20	59
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	20 participants	19 participants	20 participants	59 participants
		63.2 (11.28)	73.68 (8.38)	64.55 (7.07)	67.00 (9.36)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	20 participants	19 participants	20 participants	59 participants
	Female	6 30.0%	5 26.3%	4 20.0%	15 25.4%
	Male	14 70.0%	14 73.7%	16 80.0%	44 74.6%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	20 participants	19 participants	20 participants	59 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	2 10.0%	0 0.0%	1 5.0%	3 5.1%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	3 15.0%	5 26.3%	1 5.0%	9 15.3%
	White	15 75.0%	14 73.7%	18 90.0%	47 79.7%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Hoehn & Yahr Parkinson's Disease Severity Rating [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	20 participants	19 participants	20 participants	59 participants
		2.34 (.41)	2.42 (.42)	2.35 (.54)	2.42 (.55)
		[1] Measure Description: The Hoehn & Yahr scale measures general staging of Parkinson's disease progression. Classification ranges from 1 to 5, with higher scores indicating greater disability. The range of scale scores acceptable for this study was 1 to 3 (1 = Unilateral involvement only, usually with minimal or no functional impairment, 2 = Bilateral or midline involvement, without impairment of balance, 3= First sign of impaired righting reflexes; patients are physically capable of leading independent lives, and their disability is mild to moderate). This assessment was performed by a movement disorders specialist.

Outcome Measures

1. Primary Outcome

Title	Dual Task Function #1
Description	Dual task tested functional and cognitive performance while walking and talking simultaneously. Walking spatial and temporal parameters were measured using the Gaitrite 24 foot gaitmat with existing hardware and software for analysis. Cycle time refers to the amount of time taken for a participant to complete a single stride. Lower scores indicate better outcomes. The range of scores for Cycle Time is: Pre (0.73-2.47), Post (0.72-1.45).
Time Frame	baseline and 3 months

Outcome Measure Data

Analysis Population Description

**Please note that initiation of dual-task testing was delayed by the original PI at the start of this study, such that some early participants were missed. This caused the dual-task outcome category to have lower numbers analyzed than other outcomes.

Arm/Group Title	Arm 1: Treadmill Training	Arm 2: Memory Training	Arm 3: Treadmill and Memory Training
Arm/Group Description:	Treadmill training with aerobic exercise treadmill training: walk on treadmill for aerobic exercise	Memory training with computerized memory program computerized memory training: memory testing and training on computer program	Combination of treadmill training and computerized memory program treadmill training: walk on treadmill for aerobic exercise computerized memory training: memory testing and training on computer program
Overall Number of Participants Analyzed	8	13	15
Mean (Standard Error); Unit of Measure: seconds
Cycle Time- baseline	1.15 (0.152)	1.12 (.04)	.987 (.037)
Cycle Time- 3 months	1.068 (.0375)	1.09 (.052)	.951 (.035)

2. Primary Outcome

Title	Dual Task Function #2
Description	Dual task tested functional and cognitive performance while walking and talking simultaneously. Walking spatial and temporal parameters were measured using the Gaitrite 24 foot gaitmat with existing hardware and software for analysis. Velocity was calculated by dividing the distance by the time it takes to travel that same distance, with consideration for direction. Higher values represent better outcomes. The range of scores for this study was: Pre (36.4 - 269.4), Post (76.3 - 267.6).
Time Frame	baseline and 3 months

Outcome Measure Data

Analysis Population Description

**Please note that initiation of dual-task testing was delayed by the original PI at the start of this study, such that some early participants were missed. This caused the dual-task outcome category to have lower numbers analyzed than other outcomes.

Arm/Group Title	Arm 1: Treadmill Training	Arm 2: Memory Training	Arm 3: Treadmill and Memory Training
Arm/Group Description:	Treadmill training with aerobic exercise Treadmill training with aerobic exercise: walk on treadmill for aerobic exercise	Memory training with computerized memory program Memory training with computerized memory program: memory testing and training on computer program	Combination of treadmill training and computerized memory program Combination of treadmill training and computerized memory: both exercise and cognitive computer training
Overall Number of Participants Analyzed	8	13	15
Mean (Standard Error); Unit of Measure: cm/sec
Velocity- baseline	131.194 (19.921)	116.944 (8.213)	165.165 (11.179)
Velocity- 3 months	134.7 (9.016)	127.353 (10.177)	174.581 (12.985)

3. Primary Outcome

Title	Cognitive Function #1
Description	2-Choice Reaction Time measures patients' ability to shift mental set. One of two stimuli are presented on the screen ("+ "or "*"). Subjects press a specified response button on the keyboard corresponding to the presented stimulus. Units are "Throughput", which reflects efficiency of performance by being based on both accuracy and speed. Throughput represents correct responses/ minute.
Time Frame	baseline and 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1: Treadmill Training	Arm 2: Memory Training	Arm 3: Treadmill and Memory Training
Arm/Group Description:	Treadmill training with aerobic exercise treadmill training: walk on treadmill for aerobic exercise	Memory training with computerized memory program computerized memory training: memory testing and training on computer program	Combination of treadmill training and computerized memory program treadmill training: walk on treadmill for aerobic exercise computerized memory training: memory testing and training on computer program
Overall Number of Participants Analyzed	11	15	17
Mean (Standard Error); Unit of Measure: correct responses/ minute
Two Choice Reaction- baseline	89.3535 (6.939)	93.413 (6.227)	101.236 (4.588)
Two Choice Reaction- 3 months	105.677 (7.278)	103.4767 (5.497)	119.6465 (5.117)

4. Primary Outcome

Title	Cognitive Function #2
Description	The Stroop is a measure of selective attention and cognitive flexibility in which the subject must inhibit a preponderant response. Subjects are asked to complete three parts under timed conditions: (1) reading words describing colors written in black-and-white, (2) naming those colors when printed as X's, (3) naming the ink color when words describing the colors are mismatched with the colors (suppressing verbal content). Stroop interference scores from condition 3 are t-scores and higher scores equate with better outcomes.
Time Frame	baseline and 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1: Treadmill Training	Arm 2: Memory Training	Arm 3: Treadmill and Memory Training
Arm/Group Description:	Treadmill training with aerobic exercise Treadmill training with aerobic exercise: walk on treadmill for aerobic exercise	Memory training with computerized memory program Memory training with computerized memory program: memory testing and training on computer program	Combination of treadmill training and computerized memory program Combination of treadmill training and computerized memory: both exercise and cognitive computer training
Overall Number of Participants Analyzed	11	15	17
Mean (Standard Error); Unit of Measure: t-score
Stroop- baseline	48.37 (1.278)	41.74 (2.581)	48.4 (1.54)
Stroop- 3 months	48.9 (1.642)	47.8 (2.522)	47.941 (1.93)

5. Primary Outcome

Title	Timed Instrumental Activities of Daily Living (TIADL) Function #1
Description	The Timed IADL involves the timing of performance of 5 tasks that mimic everyday instrumental activities of daily living: 1) finding a telephone number in the telephone directory, 2) counting out correct change from a group of coins, 3) finding then reading the ingredients on a food can label, 4) finding two food items in an array of food items (shopping), 5) finding then reading the directions on a medicine container. For each task there is a 2 minute time limit, with the exception of the telephone number task which has a limit of 3 mins. If the task is not completed within the time limit it is terminated. Error codes are assigned for each task. For the tasks completed with minor errors, a time penalty of 1 SD of those who completed the task is added to the completion time. Higher single item scores mean worse performance.The times for each of the tasks are transformed into Z scores which are then summed to form a composite score. Range for shopping item (0.61- 69.9 sec)
Time Frame	baseline and 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1: Treadmill Training	Arm 2: Memory Training	Arm 3: Treadmill and Memory Training
Arm/Group Description:	Treadmill training with aerobic exercise treadmill training: walk on treadmill for aerobic exercise	Memory training with computerized memory program computerized memory training: memory testing and training on computer program	Combination of treadmill training and computerized memory program treadmill training: walk on treadmill for aerobic exercise computerized memory training: memory testing and training on computer program
Overall Number of Participants Analyzed	11	15	17
Mean (Standard Error); Unit of Measure: z-score
Timed IADL's Composite- baseline	0.131 (0.203)	.234 (.164)	-.2435 (0.080)
Timed IADL's Composite- 3 months	0.075 (.370)	.1928 (.13866)	-.34 (0.065)

6. Primary Outcome

Title	Timed Instrumental Activities of Daily Living (TIADL) Function #2
Description	The Timed IADL for Shopping involved finding two food items in an array of food items. The task was timed in seconds and if completed with minor errors, a time penalty was added to the completion time. Higher scores/times meant worse performance. The range for shopping task completion was 0.61 to 69.9 seconds.
Time Frame	baseline and 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1: Treadmill Training	Arm 2: Memory Training	Arm 3: Treadmill and Memory Training
Arm/Group Description:	Treadmill training with aerobic exercise Treadmill training with aerobic exercise: walk on treadmill for aerobic exercise	Memory training with computerized memory program Memory training with computerized memory program: memory testing and training on computer program	Combination of treadmill training and computerized memory program Combination of treadmill training and computerized memory: both exercise and cognitive computer training
Overall Number of Participants Analyzed	11	15	17
Mean (Standard Error); Unit of Measure: seconds
TIADL Shopping- baseline	7.339 (3.856)	6.01 (1.62)	3.213 (1.05)
TIADL Shopping- 3 months	3.493 (0.980)	4.746 (1.346)	2.39 (0.591)

Adverse Events

Time Frame	Adverse events were collected during a 5 month subject participation period which included 1 month of baseline testing, 3 months of intervention, and 1 month of post-testing.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Arm 1: Treadmill Training		Arm 2: Memory Training		Arm 3: Treadmill and Memory Training
Arm/Group Description	Treadmill training with aerobic exercise treadmill training: walk on treadmill for aerobic exercise		Memory training with computerized memory program computerized memory training: memory testing and training on computer program		Combination of treadmill training and computerized memory program treadmill training: walk on treadmill for aerobic exercise computerized memory training: memory testing and training on computer program
All-Cause Mortality
	Arm 1: Treadmill Training		Arm 2: Memory Training		Arm 3: Treadmill and Memory Training
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/20 (0.00%)		0/19 (0.00%)		0/20 (0.00%)
Serious Adverse Events
	Arm 1: Treadmill Training		Arm 2: Memory Training		Arm 3: Treadmill and Memory Training
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0.00%)		0/19 (0.00%)		1/20 (5.00%)
Cardiac disorders
Idiopathic orthostatic hypotension † [1]	0/20 (0.00%)	0	0/19 (0.00%)	0	1/20 (5.00%)	1
† Indicates events were collected by systematic assessment; [1] Participant arrived for study visit and per protocol blood pressure readings were taken which endorsed orthostasis. Participant was taken to ER accompanied by study staff and recovered. Orthostasis is a symptom of PD.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Arm 1: Treadmill Training		Arm 2: Memory Training		Arm 3: Treadmill and Memory Training
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/20 (25.00%)		3/19 (15.79%)		4/20 (20.00%)
General disorders
migraine headache † [1]	1/20 (5.00%)	2	0/19 (0.00%)	0	1/20 (5.00%)	1
Musculoskeletal and connective tissue disorders
fell at home † [2]	3/20 (15.00%)	5	1/19 (5.26%)	2	4/20 (20.00%)	11
Fell outside at study site † [3]	0/20 (0.00%)	0	1/19 (5.26%)	1	0/20 (0.00%)	0
muscular pain in arm † [4]	1/20 (5.00%)	3	0/19 (0.00%)	0	0/20 (0.00%)	0
aggravated pre-existing back pain † [5]	1/20 (5.00%)	2	0/19 (0.00%)	0	1/20 (5.00%)	1
dystonia † [6]	2/20 (10.00%)	2	0/19 (0.00%)	0	0/20 (0.00%)	0
Skin and subcutaneous tissue disorders
Grover's disease † [7]	0/20 (0.00%)	0	1/19 (5.26%)	1	0/20 (0.00%)	0
mild skin irritation † [8]	0/20 (0.00%)	0	0/19 (0.00%)	0	1/20 (5.00%)	1
† Indicates events were collected by systematic assessment; [1] participant experienced migraine headache at home.; [2] fall; [3] Participant fell outside study site on curb following intervention visit.; [4] participant reported arm pain while doing treadmill intervention. Physician assessed participant and suggested he might be holding too tightly to the railing. Participant reported this event on 3 different occasions.; [5] During treadmill intervention participants reported aggravated back pain.; [6] increase in PD symptom; [7] Pt diagnosed during study participation, sought treatment, and was provided prescription topical treatment.; [8] skin irritation from harness used in treadmill training intervention. Participant sought treatment, was given topical ointment, rash cleared.

Limitations and Caveats

High drop-out rate across the board, but particularly in Arm 1.

More Information

Certain Agreements

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

Results Point of Contact

• Name/Title: Fred Ivey
• Organization: VAORD
• Phone: 410-605-7000 ext 6582
• EMail: Frederick.Ivey@va.gov

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT01156714
• Other Study ID Numbers: E7158-R
• First Submitted: March 11, 2010
• First Posted: July 5, 2010
• Results First Submitted: January 19, 2018
• Results First Posted: March 5, 2019
• Last Update Posted: March 5, 2019