Aerobic Exercise in Parkinson's Disease (LTAE-PD)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03808675|
Recruitment Status : Recruiting
First Posted : January 17, 2019
Last Update Posted : August 19, 2019
|Condition or disease||Intervention/treatment||Phase|
|Parkinson's Disease||Behavioral: Aerobic walking Behavioral: Usual care with PD specific health education||Phase 2 Phase 3|
Parkinson's disease (PD) culminates in dementia, immobility, and death at a huge societal cost. Even early in the course, motor and cognitive dysfunction impairs instrumental activities of daily living (IADL). Non-motor symptoms due to fatigue, mood, sleep, and autonomic disorders further reduce quality of life (QoL). DTI shows progressive decline in brain tissue integrity. Usual care of PD centers on medical and surgical treatments relieve motor symptoms, but these cause side effects and lose efficacy over time. Usual treatment for non motor manifestations with pharmaceuticals (e.g., antidepressants) is symptomatic and not specific for PD. Acetylcholine esterase inhibitors exert modest symptomatic benefits on dementia, but there is no approved treatment for mild cognitive impairment. Physical Therapy is usually prescribed in later stages when mobility impairment ensues. There is no approved standard exercise regimen for PD. There is no cure or disease modifying treatment. Thus, there is a critical need for treatments that provide broad spectrum of benefits and slow PD.
Preliminary research suggests that aerobic exercise has potential to meet this need. However, aerobic exercise is demanding and carries some risks. It is unknown if aerobic exercise is more beneficial than usual care in PD in long term due to gaps in the investigators knowledge about the effects of cardiorespiratory fitness (CRF) on brain tissue integrity, motor function, cognition, IADL, QoL, and disease progression. Limitations of current studies include short duration, small sample size, lack or inadequacy of controls, lack of outcome measures for cognition and IADL, and lack of biological markers to measure progression. The objective in this application is to fill the translational gap by determining the biological, clinical, and functional effects of long term aerobic exercise (LTAE) in PD.
The overall hypothesis is that LTAE improves brain tissue integrity and slows down PD. The FIRST AIM is to determine the effects of LTAE on clinical features and functional abilities in PD. The investigators' prior 6-month, uncontrolled trial showed preliminary evidence that aerobic exercise improves aspects of motor function, cognition, and QoL in PD, but long term outcomes and implication for functional abilities are unknown. The investigators hypothesize that LTAE will provide sustained improvement in motor function, cognition, and non-motor symptoms with translation of benefits to QoL and IADL. The investigators will test this with a one-year randomized controlled trial (RCT) that compares the effects of moderate aerobic exercise vs usual care. The investigators will use driving as the outcome for IADL. Driving represents an important symbol for independence, and depends on integrity of cognitive and motor systems. The SECOND AIM is to determine the mechanism of LTAE effects in PD. CRF reflects complex improvements in vascular, cardiac, and metabolic health from aerobic exercise. There is preliminary evidence that higher CRF is associated with better brain health and motor/cognitive function, and that aerobic exercise improves these outcomes. For example, the investigators' preliminary study showed improvement of microtissue integrity in the striatum and white matter on DTI, but it is unclear how these changes counteract PD progression over long term. The hypotheses are: 1) LTAE will improve brain tissue integrity as indexed by DTI, 2) LTAE effects on motor and cognitive function are mediated by changes in brain tissue integrity on DTI, and 3) physiological processes leading to improved CRF from AE are critical to the benefits on the brain tissue integrity and motor/cognitive function. The investigators will test these hypotheses determining the effects of LTAE on CRF and DTI, and the association between individual differences in training related changes in motor and cognitive function, DTI, and CRF.
In summary, the investigators' proposal leverages the diverse interdisciplinary team, strong preliminary data and past work, and unique infrastructure to determine if LTAE slows down neurodegeneration and clinical disability in PD.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||100 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||One-year, single-blind, parallel group, randomized controlled trial (RCT) that compares the effects of moderate aerobic exercise vs. usual care + health education|
|Masking:||Single (Outcomes Assessor)|
|Masking Description:||Due to nature of the intervention (exercise), the participant cannot be blinded. However, assessors for various outcomes will be blinded to the group status.|
|Official Title:||Long Term Aerobic Exercise to Slow Progression in Parkinson's Disease|
|Actual Study Start Date :||July 1, 2019|
|Estimated Primary Completion Date :||June 30, 2023|
|Estimated Study Completion Date :||June 30, 2023|
Participants randomized to aerobic exercise
Behavioral: Aerobic walking
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.
Participants randomized to usual care with PD specific health education
Behavioral: Usual care with PD specific health education
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
- OFF period MDS-UPDRS Motor Subscale score [ Time Frame: Change from Baseline OFF period MDS-UPDRS Motor Subscale score at 1 year ]Motor function. MDS-UPDRS motor examination subscale (Part III) score in the "practically defined OFF state", i.e., after overnight (~12 hours) withdrawal of PD medications. Higher scores worse. Range: 0-132.
- Percent Increase Score (PIS) on Eriksen's flanker task [ Time Frame: Change from Baseline Percent Increase Score (PIS) on Eriksen's flanker task at 1 year ]Cognitive function. Due to its sensitivity to changes in aerobic fitness (including in the investigators' preliminary study), the investigators chose change in Percent Increase Score (PIS) on Eriksen's flanker task, which measures the cost of conflict resolution between the incongruent and congruent stimuli. Higher scores worse.
- total number of driving safety errors on road test [ Time Frame: Change from Baseline total number of driving safety errors on road test at 1 year ]Driving. The video of a standardized experimental drive in an instrumented vehicle will be scored for safety errors by a certified driving instructor. Higher scores worse.
- regional DTI (diffusion tensor imaging) [ Time Frame: Change from Baseline regional DTI at 1 year ]Brain tissue integrity. The investigators will analyze differences in regional rD (radial diffusivity) changes between the aerobic exercise and usual care control groups in primary outcome regions of interest (Putamen, Cingulum, Superior Longitudinal Fasciculus). Higher scores worse.
- MDS-UPDRS Non-motor Experiences of Daily Living subscale (Part I) score [ Time Frame: Change from Baseline MDS-UPDRS Non-motor Experiences of Daily Living subscale (Part I) score at 1 year ]Non-motor symptoms. Higher scores worse. Range: 0-48
- Summary index of the Parkinson's Disease Questionnaire-39 (PDQ-39) [ Time Frame: Change from Baseline PDQ-39 Summary Index at 1 year ]Quality of life
- ON Period MDS-UPDRS motor examination subscale score [ Time Frame: Change from Baseline ON Period MDS-UPDRS motor examination subscale score at 1 year ]Motor function. Higher scores worse. Range: 0-132.
- Dexterity (time on 9-hole peg board) test of NIH Toolbox motor battery [ Time Frame: Change from Baseline 9-hole peg board test performance at 1 year ]Motor function. Dexterity
- COGSTAT score [ Time Frame: Change from Baseline COGSTAT score at 1 year ]Cognitive function. COGSTAT, a composite measure of cognition, calculated by assigning and summing standard T-scores (mean=50, SD=10) to eight tests from the cognitive test battery the investigators used in the driving studies, will be the main secondary outcome measure. This cognitive battery will enable us to probe multiple domains: Complex Figure Test-Copy (CFT-Copy) Version, Block Design for visuospatial construction; Trail-making Test (B-A), a measure of set shifting and Controlled Oral Word Association Test (also tests language) for executive functions; Rey Auditory Verbal Learning Test (anterograde verbal memory), CFT-Recall is administered 30 minutes after the CFT-Copy (visual memory), Benton Visual Retention Test errors for memory; Judgment of Line Orientation for visual perception. Higher scores worse.
- Radial Diffusivity (rD) on Diffusion imaging tractography [ Time Frame: Change from Baseline Diffusion imaging tractography at 1 year ]Brain tissue integrity. Motor: Substantia nigra <-> putamen (nigrostriatal tract) and putamen <-> premotor cortex Cognitive: Dorsal lateral prefrontal cortex (DLPFC) <-> caudate and the parietal cortex <-> prefrontal cortex. Higher scores worse.
- Geriatric Depression Scale (GDS) score [ Time Frame: Change from Baseline GDS score at 1 year ]Severity of depression. Higher scores worse. Range: 0-15
- Motor experiences of daily living score [ Time Frame: Change from Baseline motor experiences of daily living score at 1 year ]Motor function. Higher scores worse. Range:0-52.
- Beck Anxiety Inventory (BAI) score [ Time Frame: Change from Baseline BAI score at 1 year ]Anxiety severity. Higher scores worse. Range: 0-63
- Parkinson's Disease Sleep Scale version 2 (PDSS-2) [ Time Frame: Change from Baseline PDSS-2 score at 1 year ]Sleep quality. Higher scores worse. Range: 0-60
- Fatigue Severity Scale (FSS) [ Time Frame: Change from Baseline FSS score at 1 year ]Severity of fatigue. Higher scores worse. Range: 9-63
- Locomotion (time on 4-m walk test for gait speed) test of NIH Toolbox motor battery [ Time Frame: Change from Baseline Locomotion (time on 4-m walk test for gait speed) test performance at 1 year ]Motor function. Locomotion
- Endurance (distance on 6-minute walk) test [ Time Frame: Change from Baseline Endurance (distance on 6-minute walk) test performance at 1 year ]Motor function. Endurance (6-minute walk).
- VO2max on cycle ergometry [ Time Frame: Change from Baseline VO2max on cycle ergometry at 1 year ]Cardiorespiratory fitness as an index of aerobic exercise intervention delivery. Higher scores better.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03808675
|Contact: Ergun Y Uc, MD||(319) email@example.com|
|Contact: Christina M Weber, BA||(608) firstname.lastname@example.org|
|United States, Iowa|
|University of Iowa Hospitals & Clinics||Recruiting|
|Iowa City, Iowa, United States, 52242|
|Contact: Ergun Y Uc, MD 319-356-4757 email@example.com|
|Contact: Christina M Weber, BA 3194672906 firstname.lastname@example.org|
|Iowa City VA Health Care System, Iowa City, IA||Recruiting|
|Iowa City, Iowa, United States, 52246-2208|
|Contact: Ergun Y Uc, MD 319-356-4757 email@example.com|
|Principal Investigator: Ergun Y. Uc, MD|
|Principal Investigator:||Ergun Y. Uc, MD||Iowa City VA Health Care System, Iowa City, IA|