Aerobic Exercise in Parkinson's Disease

NCT03808675 | Completed Results DMC

• 2 other identifiers: E2987-R1I01RX002987-01A1
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 2

Brief Summary

Parkinson's disease (PD) is an incurable brain illness that afflicts more than one million Americans, including many aging Veterans. PD places an unbearable burden on the individual due to progressive impairment of movement and mental function. As a result, patients lose critical abilities such as driving and can become isolated. Although drugs and surgery help movement problems, their benefits are temporary and may cause side effects. Drugs provide limited and temporary benefit for cognition and do not prevent dementia. Animal and preliminary human studies on aerobic exercise show promising results in helping a broad spectrum of symptoms. However, due to limited and inconsistent research results, the long term effects of aerobic exercise on brain health and clinical features in PD is unknown. The investigators will conduct a clinical trial to test the long term effects of aerobic exercise on the brain tissue, movement, mental functions, and driving in PD. If effective, aerobic exercise can be implemented immediately as a low cost, easily accessible treatment in PD.

Conditions

Parkinson's Disease

Keywords

Parkinson's disease; Exercise; Aerobic exercise; Cognition; Driving; Diffusion tensor imaging; DTI; MRI; Depression; Cardiorespiratory Fitness; Quality of life; Health education; Executive functions

Outcome Measures

Primary Outcomes (7)

• Change in MDS-UPDRS Part III Motor (OFF) Score

  Measures change in the severity of parkinsonism. Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Motor section (Part III), measured in the "practically defined" OFF state (after overnight, \~12 hours, withdrawal of PD medications). It measures specific signs like rigidity, tremor, bradykinesia (slowness of movement), and gait abnormalities by a certified rater. Each item is rated 0-4: 0 - Normal (no impairment), 1 - Slight, 2- Mild, 3 - Moderate, 4 - Severe. Total score is reported (range 0-132). Higher scores worse for individual data points. Lower value better for change score.

  Final Visit at 1 year - Baseline

• Change in Flanker Task

  Measures change in the executive function domains of inhibitory control and attention. Uncorrected Standard Score of the NIH Toolbox Flanker Inhibitory Control and Attention Test. The Raw Score is based on number correct × average reaction time (accuracy \& speed composite). The Uncorrected Standard Score is based on age-normed raw score with mean = 100 and SD = 15. Score range 40-160 with interpretation below: ≥ 130 - Very Superior, 115-129 - Superior, 85-114 - Average, 70-84 - Below Average, \< 70 - Impaired / markedly low attention control. Higher scores better for individual data points. Higher value better for change score.

  Final visit at 1 year - Baseline

• Change in Road Safety Error Count

  Number of safety errors made during an experimental real-world road drive test, scored by a certified driving instructor per criteria in the Iowa Department of Transportation's Drive Test Scoring Standards. Higher error count score worse. Lower scores better for change score.

  Final Visit at 1 year - Baseline

• Change in the Parkinson's Disease Questionnaire-39 (PDQ-39) Score

  Questionnaire regarding activities of daily living and ability within the last month. PDQ-39 has 8 domains: Mobility (10 items) → max = 40, Activities of daily living (6 items) → max = 24, Emotional well-being (6 items) → max = 24, Stigma (4 items) → max = 16, Social support (3 items) → max = 12, Cognitions (4 items) → max = 16, Communication (3 items) → max = 12, Bodily discomfort (3 items) → max = 12. Domain Score=(Sum of item scores/Maximum possible)\*100 . The main outcome measure is PDQ-39 Summary Index (PDQ-39 SI) is the mean of the 8 domain scores (range = 0 to 100). Higher scores at datapoints are worse. Lower change score is better.

  Final Visit at 1 year - Baseline

• Change in Cingulum Cingulate Radial Diffusivity (rD)

  Brain tissue integrity. Change in regional diffusion coefficient for radial diffusivity (rD) on DTI. Higher scores worse at individual data points. Lower scores better for change.

  Final Visit at 1 year - Baseline

• Change in Superior Longitudinal Fasciculus Radial Diffusivity (rD)

  Brain tissue integrity. Change in regional diffusion coefficient for radial diffusivity (rD) on DTI. Higher scores worse at individual data points. Lower scores better for change.

  Final Visit at 1 year - Baseline

• Change in Putamen Radial Diffusivity

  Brain tissue integrity. Change in regional diffusion coefficient for radial diffusivity (rD) on DTI. Higher scores worse at individual data points. Lower scores better for change.

  Final Visit at 1 year - Baseline

Secondary Outcomes (23)

• Change in MDS-UPDRS Non-motor Experiences of Daily Living Subscale (Part I) Score

  Final Visit at 1 year - Baseline

• Change in MDS-UPDRS Motor Experiences of Daily Living Score (Part II)

  Final Visit at 1 year - Baseline

• Change in ON Period MDS-UPDRS Motor Examination Subscale Score (Part 3)

  Final Visit at 1 year - Baseline

• Change in MDS-UPDRS Dyskinesia and Motor Fluctuations (Part 4)

  Final Visit at 1 year - Baseline

• Change in Total MDS-UPDRS Score

  Final Visit at 1 year - Baseline

Other Outcomes (2)

• Change in VO2max on Cycle Ergometry

  Final Visit at 1-year - Baseline

• Change in L-dopa Equivalent Daily Dose (LEDD)

  Final visit at 1-year - Baseline

Study Arms (2)

Aerobic

EXPERIMENTAL

Participants randomized to aerobic exercise

Behavioral: Aerobic walking

Control

OTHER

Participants randomized to usual care with PD specific health education

Behavioral: Usual care with PD specific health education

Interventions

Aerobic walking BEHAVIORAL

The investigators will use self-administered continuous walking exercise at a moderate intensity level, defined as 40-59% of heart rate reserve or 64-77% of heart rate at gas exchange threshold (HRGET) by ACSM as in the investigators' preliminary study (PMID: 24991037 PMCID: PMC4132568). The HRGET will be determined as the heart rate at VO2max during graded cycle ergometry. The total duration of the exercises will be 150 min/week per 2008 Physical Activity Guidelines for Americans and American Heart Association recommendations, conducted in three 50 min sessions. The aerobic walking intervention will take place outdoors (e.g., trails, sidewalks, parks) or indoors (e.g., track in a local gym or a mall) depending on the preferences of the subject and weather. Session duration will be 20 min the first week and will be advanced by 5 min per week over 6 weeks.

Aerobic

Usual care with PD specific health education BEHAVIORAL

In this study, patients will receive their usual medical treatment for motor and non-motor symptoms from their primary neurologist. The investigators will use a streamlined form of PD specific health education prepared by the VA: My Parkinson's Story, which consists of a series of short videos prepared by the VA PADRECCs addressing various aspects of PD. These 6-12 minutes long videos are freely available on YouTube. The investigators can also provide them on a CD if subjects desire. They start with a patient testimony about the topic of the episode, followed by comments of experts in the field. The title of the episodes are: Early Parkinson's, Medications, Exercise, Memory, Visual Disturbances, Depression, Sleep, Speech and Swallowing, Impulsive Behaviors, Driving, Pain, Dyskinesias, Deep Brain Stimulation, Advanced Parkinson's Disease, Falls, The Caregiver, Hospitalization, Genetics, Environmental Exposure, Atypical Parkinsonism

Control

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women aged 40 and older with the diagnosis of idiopathic PD per UK Brain Bank criteria
• Hoehn-Yahr Stage I-III, on stable dopaminergic treatment regimen for equal or greater than 4 weeks prior to baseline.
• Aerobic Fitness: VO2max below "very good" fitness levels for their age and gender at baseline cyle ergometry.
• To include subjects who have room to improve their aerobic fitness, the investigators will enroll only those subjects whose VO2max is below "very good" fitness level (about 90% of the population) using age and gender based VO2max norms based review of 62 studies where VO2max was measured directly in healthy adult subjects in the USA, Canada and 7 European countries (Reference: Shvartz, E and Reibold, RC. Aerobic fitness norms for males and females aged 6 to 75 years: a review.
• Aviat Space Environ Med. 1990; 61:3-11).
• Cognitive function: No dementia per Movement Disorder Society Level I criteria (Reference: Dubois, B, Burn, D, Goetz, C, et al. Diagnostic procedures for Parkinson's disease dementia: recommendations from the movement disorder society task force. Mov Disord. 2007; 22:2314-2324).
• Current active drivers with a valid driver's license
• Veteran or non-veteran

You may not qualify if:

• Subjects unwilling or unable to give informed consent
• Secondary parkinsonism (e.g., drug induced)
• Parkinson-plus syndromes
• History of brain surgery for PD such as deep brain stimulation
• Corrected visual acuity less than 20/50 (due to effect on driving)
• Contraindications to exercise per ACSM criteria for Exercise Testing and Training (Reference: American College of Sports Medicine. Cardiorespiratory Exercise Prescription. In: Ehrman JK, ed. ACSM's Guidelines for Exercise Testing and Prescription.6th ed. Baltimore: Lippincott Williams \& Wilkins, 2010:448-462).
• No confounding acute or unstable medical, psychiatric, orthopedic condition. Subjects who have hypertension, diabetes mellitus, depression, or other common age related illness will be included if their disease under control with stable treatment regimen for at least 30 days.
• Clinically significant TBI or PTSD
• Presence of other known medical or psychiatric comorbidity that in the investigator's opinion would compromise participation in the study
• Presence of dementia per Movement Disorder Society Level I criteria
• Subjects with clinically significant depression as determined by a Beck Depression Inventory (BDI) score greater than 15 at the screening visit
• History of exposure to typical or atypical antipsychotics or other dopamine blocking agents within 6 months prior to the baseline visit
• Use of investigational drugs within 30 days before screening
• Subjects have to be on a stable regimen of central nervous system acting medications (benzodiazepines, antidepressants, hypnotics) for 30 days prior to the baseline visit
• Contraindication to having a brain MRI

Sponsors & Collaborators

• VA Office of Research and Development: lead
• University of Iowa: collaborator

Study Sites (2)

University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242, United States

Location

Iowa City VA Health Care System, Iowa City, IA

Iowa City, Iowa, 52246-2292, United States

Location

Related Publications (1)

• Uc EY, Doerschug KC, Magnotta V, Dawson JD, Thomsen TR, Kline JN, Rizzo M, Newman SR, Mehta S, Grabowski TJ, Bruss J, Blanchette DR, Anderson SW, Voss MW, Kramer AF, Darling WG. Phase I/II randomized trial of aerobic exercise in Parkinson disease in a community setting. Neurology. 2014 Jul 29;83(5):413-25. doi: 10.1212/WNL.0000000000000644. Epub 2014 Jul 2.

  PMID: 24991037 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease; Motor Activity; Depression; Health Education

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Behavior; Behavioral Symptoms; Adherence Interventions; Medication Adherence; Patient Compliance; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior

Limitations and Caveats

Our target effective sample size was 68 subjects. We enrolled 57 subjects and 53 completed the study. Due to COVID-19 related barriers, we reached 78% of our target effective sample size decreasing the power of the study reaching significant results. We used Ratings of Perceived Exertion for exercise prescription, which might have resulted in low-dose delivery of exercise in the Active group. Both groups exercised outside of the study that might have reduced group differences on outcomes.

Results Point of Contact

• Title: Ergun Uc, MD
• Organization: Iowa City VA Health Care System/University of Iowa Health Care

ergun-uc@uiowa.edu

319-356-1616

Study Officials

• Ergun Y. Uc, MD

  Iowa City VA Health Care System, Iowa City, IA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Due to nature of the intervention (exercise), the participant cannot be blinded. However, assessors for various outcomes will be blinded to the group status.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: One-year, single-blind, parallel group, randomized controlled trial (RCT) that compares the effects of moderate aerobic exercise vs. usual care + health education

Study Record Dates

• First Submitted: January 7, 2019
• First Posted: January 17, 2019
• Study Start: July 1, 2019
• Primary Completion: September 30, 2024
• Study Completion: September 30, 2024
• Last Updated: March 12, 2026
• Results First Posted: March 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Time Frame: As per VA specifications.
• Access Criteria: As per VA specifications.

Locations

US (2)