Over the past decade a burgeoning literature suggests that exercise has a therapeutic benefit in both patients with Parkinson's disease (PD) and in animal models of PD, especially when animals exercise at high intensity. Although many studies have been conducted and conventional wisdom acknowledges the beneficial effects of exercise, there have been no studies of: 1) the benefits of exercise in PD patients who have not yet started dopamine replacement therapy (patients with de novo PD), and 2) the dose-response effects of """"""""moderate"""""""" versus """"""""vigorous"""""""" exercise to attenuate the progression of PD symptoms in patients with de novo PD. Accordingly, the long-range goal is to determine whether exercise should be first-line therapy for de novo PD. As the first step in accomplishing our long-term goal, we will conduct a multi-center, randomized, controlled, single-blinded study of two intensities of endurance exercise over six months;we will also have a control """"""""no- exercise"""""""" group. The two levels of exercise are moderate (4 days/wk at 60%-65% HRmax) and vigorous (4 days/wk at 80%-85% HRmax). We are proposing three aims.
Aim 1 is to find out if patients can exercise at the higher level of intensity.
Aim 2 is to find out if either or both of the exercie intensities yield benefits consistent with meaningful clinical change in the Unified Parkinson's Disease Rating Scale (UPDRS) (non-futility).
Aim 3 is to document key responses associated with clinical trials, such as adverse events and attrition. Upon the completion of this study we will be well-positioned to conduct a phase III clinical trial if the futility trial is successful. e currently envision 6 possible successful scenarios based on the results of this exploratory study. These scenarios clearly indicate what parameters will be tested in the phase III clinical trial. Th scenarios are based not only on the outcome of the futility trial (Aim 2) but also on %HRmax attained and average number of days exercised (Aim 1). All 3 components are critical in planning the next study investigating exercise in PD. We also recognize the possibility the trial will be declared futile, which will force us to reconsider the therapeutic value of exercise for PD

Public Health Relevance

Individuals with Parkinson's disease (PD) suffer from a slow and steady increase in symptoms of the disease and a progressive decline in function. Substantial evidence over the last decade suggests that endurance exercise can reduce the symptoms of the disease. This proposed phase II randomized clinical trial is designed to determine parameters of exercise intensity that attenuate progression of symptoms of PD. Upon the completion of this study, we will have defined the needed parameters for a phase III clinical trial.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS074343-04
Application #
8726498
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Galpern, Wendy R
Project Start
2011-09-30
Project End
2015-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Physical Medicine & Rehab
Type
Schools of Medicine
DUNS #
City
Aurora
State
CO
Country
United States
Zip Code
80045
David, Fabian J; Goelz, Lisa C; Tangonan, Ruth Z et al. (2018) Bilateral deep brain stimulation of the subthalamic nucleus increases pointing error during memory-guided sequential reaching. Exp Brain Res 236:1053-1065
Jinnah, H A; Comella, Cynthia L; Perlmutter, Joel et al. (2018) Longitudinal studies of botulinum toxin in cervical dystonia: Why do patients discontinue therapy? Toxicon 147:89-95
Christiansen, Cory; Moore, Charity; Schenkman, Margaret et al. (2017) Factors Associated With Ambulatory Activity in De Novo Parkinson Disease. J Neurol Phys Ther 41:93-100
O'Keefe, Joan A; Robertson-Dick, Erin E; Hall, Deborah A et al. (2016) Gait and Functional Mobility Deficits in Fragile X-Associated Tremor/Ataxia Syndrome. Cerebellum 15:475-82
Fraint, Avram; Vittal, Padmaja; Comella, Cynthia (2016) Considerations on patient-related outcomes with the use of botulinum toxins: is switching products safe? Ther Clin Risk Manag 12:147-54
Brody, David M; Litvan, Irene; Warner, Steve et al. (2016) Relationship between uric acid levels and progressive supranuclear palsy. Mov Disord 31:663-7
Comella, Cynthia L; Perlmutter, Joel S; Jinnah, Hyder A et al. (2016) Clinimetric testing of the comprehensive cervical dystonia rating scale. Mov Disord 31:563-9
Litvan, Irene; Lees, Peter S J; Cunningham, Christopher R et al. (2016) Environmental and occupational risk factors for progressive supranuclear palsy: Case-control study. Mov Disord 31:644-52
Norris, Scott A; Jinnah, H A; Espay, Alberto J et al. (2016) Clinical and demographic characteristics related to onset site and spread of cervical dystonia. Mov Disord 31:1874-1882
LaHue, Sara C; Comella, Cynthia L; Tanner, Caroline M (2016) The best medicine? The influence of physical activity and inactivity on Parkinson's disease. Mov Disord 31:1444-1454

Showing the most recent 10 out of 13 publications