Trial Outcomes & Findings for Effects of Aerobic Exercise in Parkinson's Disease (NCT NCT00784563)

NCT ID: NCT00784563

Last Updated: 2015-09-15

Results Overview

VO2max after the training - VO2max at baseline (Adjusted for levodopa-equivalent, year, training mode, setting). Please see publication PMID: 24991037 for details.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 104 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2015-09-15

Participant Flow

After phone screening, we evaluated 104 eligible candidates in-person (90 community responders to newspaper advertisements and 14 clinic patients).

Of the 104 consented candidates, 60 participants started the intervention. Thirty-six candidates did not meet eligibility criteria and 8 declined participation due to time commitment.

Participant milestones

Measure	Continuous Training - Years 1 & 2 The duration of exercise sessions (3x/week) was advanced from 15 to 45 minutes over the first 6 weeks. Participants were asked to wear electronic heart rate and walking speed monitors (Polar RS400, Kempele, Finland) and fill out diaries for each session. The goal for continuous training was to remain within 70-80% of HRmax throughout the session.	Interval Training - Years 1 & 2 The duration of exercise sessions (3x/week) was advanced from 15 to 45 minutes over the first 6 weeks. Participants were asked to wear electronic heart rate and walking speed monitors (Polar RS400, Kempele, Finland) and fill out diaries for each session. Interval trainees alternated every 3 minutes between slower (60-70% of HRmax) and faster (80-90% of HRmax) walking.	Continuous Training - Year 3 Participant were assigned to continuous training without randomization.
Years 1 & 2 STARTED	21	22	0
Years 1 & 2 COMPLETED	18	17	0
Years 1 & 2 NOT COMPLETED	3	5	0
Year 3 STARTED	0	0	17
Year 3 COMPLETED	0	0	14
Year 3 NOT COMPLETED	0	0	3

Reasons for withdrawal

Measure	Continuous Training - Years 1 & 2 The duration of exercise sessions (3x/week) was advanced from 15 to 45 minutes over the first 6 weeks. Participants were asked to wear electronic heart rate and walking speed monitors (Polar RS400, Kempele, Finland) and fill out diaries for each session. The goal for continuous training was to remain within 70-80% of HRmax throughout the session.	Interval Training - Years 1 & 2 The duration of exercise sessions (3x/week) was advanced from 15 to 45 minutes over the first 6 weeks. Participants were asked to wear electronic heart rate and walking speed monitors (Polar RS400, Kempele, Finland) and fill out diaries for each session. Interval trainees alternated every 3 minutes between slower (60-70% of HRmax) and faster (80-90% of HRmax) walking.	Continuous Training - Year 3 Participant were assigned to continuous training without randomization.
Years 1 & 2 Withdrawal by Subject	3	2	0
Years 1 & 2 Adverse Event	0	3	0
Year 3 Withdrawal by Subject	0	0	2
Year 3 Adverse Event	0	0	1

Baseline Characteristics

Effects of Aerobic Exercise in Parkinson's Disease

Baseline characteristics by cohort

Measure	Continuous Training-Years 1 & 2 n=21 Participants Participants who were randomized to continuous training in the first 2 years of the study.	Interval Training -Years 1 & 2 n=22 Participants Participants who were randomized to interval training in the first 2 years of the study.	Continuous-Year 3 n=17 Participants Participants who were assigned to continuous training in the third year of the study without randomization. Due to potentially increased risk of knee pain without additional fitness benefits, we dropped the interval group for the third year.	Total n=60 Participants Total of all reporting groups
Age, Continuous	67.6 Years STANDARD_DEVIATION 7.5 • n=5 Participants	64.7 Years STANDARD_DEVIATION 5.2 • n=7 Participants	63.7 Years STANDARD_DEVIATION 4.9 • n=5 Participants	65.4 Years STANDARD_DEVIATION 6.2 • n=4 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	7 Participants n=7 Participants	6 Participants n=5 Participants	19 Participants n=4 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	15 Participants n=7 Participants	11 Participants n=5 Participants	41 Participants n=4 Participants
Region of Enrollment United States	21 participants n=5 Participants	22 participants n=7 Participants	17 participants n=5 Participants	60 participants n=4 Participants
Education	15.9 years STANDARD_DEVIATION 2.3 • n=5 Participants	14.6 years STANDARD_DEVIATION 2.3 • n=7 Participants	14.8 years STANDARD_DEVIATION 2.1 • n=5 Participants	15.1 years STANDARD_DEVIATION 2.3 • n=4 Participants
Disease duration (years)	8.0 years STANDARD_DEVIATION 6.3 • n=5 Participants	5.3 years STANDARD_DEVIATION 3.5 • n=7 Participants	2.8 years STANDARD_DEVIATION 2.5 • n=5 Participants	5.5 years STANDARD_DEVIATION 4.9 • n=4 Participants
modified Hoehn-Yahr Scale	2.0 units on a scale n=5 Participants	2.0 units on a scale n=7 Participants	1.0 units on a scale n=5 Participants	2.0 units on a scale n=4 Participants
UPDRS- Section III score	19.6 units on a scale STANDARD_DEVIATION 9.9 • n=5 Participants	18.9 units on a scale STANDARD_DEVIATION 10.5 • n=7 Participants	17.0 units on a scale STANDARD_DEVIATION 10.0 • n=5 Participants	18.6 units on a scale STANDARD_DEVIATION 10.0 • n=4 Participants
Levodopa equivalent/day	531 mg/day STANDARD_DEVIATION 383 • n=5 Participants	601 mg/day STANDARD_DEVIATION 273 • n=7 Participants	394 mg/day STANDARD_DEVIATION 334 • n=5 Participants	540 mg/day STANDARD_DEVIATION 380 • n=4 Participants
VO2max	23.4 ml/min/kg STANDARD_DEVIATION 5.6 • n=5 Participants	25.1 ml/min/kg STANDARD_DEVIATION 8.2 • n=7 Participants	27.8 ml/min/kg STANDARD_DEVIATION 3.7 • n=5 Participants	25.2 ml/min/kg STANDARD_DEVIATION 6.5 • n=4 Participants
Montreal Cognitive Assessment	24.7 units on a scale STANDARD_DEVIATION 2.8 • n=5 Participants	24.2 units on a scale STANDARD_DEVIATION 3.0 • n=7 Participants	24.5 units on a scale STANDARD_DEVIATION 2.9 • n=5 Participants	24.5 units on a scale STANDARD_DEVIATION 2.9 • n=4 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Because all treatment arms were designed to deliver a similar average aerobic intensity, we planned to pool a priori all completers from the Continuous and Interval Training Arms for all analyses.

VO2max after the training - VO2max at baseline (Adjusted for levodopa-equivalent, year, training mode, setting).

Please see publication PMID: 24991037 for details.

Outcome measures

Measure	Completers n=49 Participants The participants who completed 6 months of aerobic training
Change in Aerobic Fitness	1.56 ml/min/kg Standard Deviation 2.74

SECONDARY outcome

Timeframe: 6 months

Population: See PMID: 24991037

Time complete the 7 m Walk test after 6 months aerobic training - Time complete the 7 m Walk test at baseline

Outcome measures

Measure	Completers n=49 Participants The participants who completed 6 months of aerobic training
Change in 7 Meter Walk Time	-0.85 seconds Standard Deviation 0.94

SECONDARY outcome

Timeframe: 6 months

=Score after 6 months training - baseline score Unified Parkinson's Disease Rating Scale (UPDRS) is an ordinal scale with all items scored from 0=normal function to 4=very severely disabled. It has 3 sections: I) Mental, Behavior, and Mood: Comprises four questions on intellectual impairment, thought disorder, depression, and apathy (scores range 0-16). II) The Activities of Daily Living (ADL) subscale is based on interview and comprises 13 items (scores range 0-52). III) UPDRS motor section is based on physical examination evaluates the components of parkinsonism (tremor, rigidity, bradykinesia, gait/posture). There are 27 items resulting in a maximum score of 108. Higher scores are worse.

Outcome measures

Measure	Completers n=49 Participants The participants who completed 6 months of aerobic training
Change in the UPDRS Section I Score	-0.5 units on a scale Standard Deviation 1.6

SECONDARY outcome

Timeframe: 6 months

=Score after 6 months training - baseline score Unified Parkinson's Disease Rating Scale (UPDRS) is an ordinal scale with all items scored from 0=normal function to 4=very severely disabled. It has 3 sections: I) Mental, Behavior, and Mood: Comprises four questions on intellectual impairment, thought disorder, depression, and apathy (scores range 0-16). II) The Activities of Daily Living (ADL) subscale is based on interview and comprises 13 items (scores range 0-52). III) UPDRS motor section is based on physical examination evaluates the components of parkinsonism (tremor, rigidity, bradykinesia, gait/posture). There are 27 items resulting in a maximum score of 108. Higher scores are worse.

Outcome measures

Measure	Completers n=49 Participants The participants who completed 6 months of aerobic training
Change in UPDRS Section II Score	-0.4 units on a scale Standard Deviation 2.4

SECONDARY outcome

Timeframe: 6 months

=Score after 6 months training - baseline score Unified Parkinson's Disease Rating Scale (UPDRS) is an ordinal scale with all items scored from 0=normal function to 4=very severely disabled. It has 3 sections: I) Mental, Behavior, and Mood: Comprises four questions on intellectual impairment, thought disorder, depression, and apathy (scores range 0-16). II) The Activities of Daily Living (ADL) subscale is based on interview and comprises 13 items (scores range 0-52). III) UPDRS motor section is based on physical examination evaluates the components of parkinsonism (tremor, rigidity, bradykinesia, gait/posture). There are 27 items resulting in a maximum score of 108. Higher scores are worse.

Outcome measures

Measure	Completers n=49 Participants The participants who completed 6 months of aerobic training
Change in the UPDRS Section III Score	-3.4 units on a scale Standard Deviation 7.0

SECONDARY outcome

Timeframe: 6 months

=Score after 6 months training - baseline score The total UPDRS score is calculated by adding Section I, Section II, and Section III scores (below). Higher scores are worse. The score ranges 0-176.

Unified Parkinson's Disease Rating Scale (UPDRS) is an ordinal scale with all items scored from 0=normal function to 4=very severely disabled. It has 3 sections: I) Mental, Behavior, and Mood: Comprises four questions on intellectual impairment, thought disorder, depression, and apathy (scores range 0-16). II) The Activities of Daily Living (ADL) subscale is based on interview and comprises 13 items (scores range 0-52). III) UPDRS motor section is based on physical examination evaluates the components of parkinsonism (tremor, rigidity, bradykinesia, gait/posture). There are 27 items resulting in a maximum score of 108.

Outcome measures

Measure	Completers n=49 Participants The participants who completed 6 months of aerobic training
Change in the Total UPDRS Score	-3.8 units on a scale Standard Deviation 7.4

SECONDARY outcome

Timeframe: 6 months

=Score after 6 months training - baseline score. MOCA=Montreal Cognitive Training Assessment Scores range 0-30, higher is better.

Outcome measures

Measure	Completers n=49 Participants The participants who completed 6 months of aerobic training
Change in the MOCA Score	0.4 units on a scale Standard Deviation 1.8

SECONDARY outcome

Timeframe: 6 months

performance on the Eriksen's flanker task (see PMID: 24991037). Participants were asked to identify the orientation of a central arrow cue ('<' or '>'), which was flanked on both sides by two arrow cues that either pointed in the same direction (congruent: <<<<<) or a different direction (incongruent: >><>>). Using reaction times (RT) during congruent and incongruent trials, the PIS was calculated as =((RT_incongruent - RT_congruent) / RT_congruent) * 100. Higher PIS is worse.

Outcome measures

Measure	Completers n=49 Participants The participants who completed 6 months of aerobic training
Change in Percent Increase Score (PIS) on Eriksen's Flanker Task	-2.41 Percentage of Increase score Standard Deviation 7.26

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 months

=Score after 6 months of training - baseline score. The Fatigue Severity Scale (FSS) is a self-administered unidimensional generic 9-item fatigue rating scale. These are rated on a seven-grade Likert scale of which only the respective ends are defined (''completely disagree''=1 to ''completely agree''=7). The total FSS score represents the mean score of each of the nine items, yielding a score range between 1 and 7, higher scores indicating a higher level of fatigue.

Outcome measures

Measure	Completers n=49 Participants The participants who completed 6 months of aerobic training
Change in Fatigue Severity Scale Score	-0.29 units on a scale Standard Deviation 1.29

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 months

=Score after 6 months training - score at baseline. The Geriatric Depression Scale (GDS)-short form is a 15 item yes/no questionnaire. The range is 0-15 and scores >5 suggest depression. Higher scores are worse.

Outcome measures

Measure	Completers n=49 Participants The participants who completed 6 months of aerobic training
Change in Geriatric Depression Scale Score	-2.09 units on a scale Standard Deviation 2.33

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 months

= PDQUALIF score after 6 months training - baseline score The PDQUALIF is a 32 item questionnaire resulting in 7 factors. . Subjects rate themselves between 1 (most favorable) and 5 (least favorable) on a Likert scale. Factor scores are standardized to100 and lower scores are better. The outcome measure is the average of these 7 factor scores.

Outcome measures

Measure	Completers n=49 Participants The participants who completed 6 months of aerobic training
Change in Parkinson's Disease Quality of Life Scale (PDQUALIF) Score	-1.62 units on a scale Standard Deviation 3.95

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 months

=amount after 6 months training - amount at baseline Total antiparkinsonian treatment daily dose expressed in levodopa equivalents per Tomlinson et al (PMID:21069833). Higher scores are worse.

Outcome measures

Measure	Completers n=49 Participants The participants who completed 6 months of aerobic training
Change in LEDD (Levodopa Equivalent Daily Dose)	34 mg/day Standard Deviation 114

Adverse Events

Continuous Training

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Interval Training

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Continuous Training n=38 participants at risk This group consists of 21 subjects who were randomized to continuous training in the first two years of the study and 17 subjects who were assigned to continuous training without randomization in the third year of the study. Thus, total group size is 38.	Interval Training n=22 participants at risk This group consists of 22 subjects who were randomized to interval training in the first two years of the study. No subjects were assigned to the interval training in the third year of the study.
Musculoskeletal and connective tissue disorders musculoskeletal pain	2.6% 1/38 • Number of events 1 • 6 months	13.6% 3/22 • Number of events 3 • 6 months

Additional Information

Ergun Y. Uc, MD

Veterans Affairs Medical Center of Iowa City

Phone: 319-356-8753

Email: ergun-uc@uiowa.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place