Study in Parkinson's disease of exercise phase 3 (SPARX3): study protocol for a randomized controlled trial

Charity G Patterson, Elizabeth Joslin, Alexandra B Gil, Wendy Spigle, Todd Nemet, Lana Chahine, Cory L Christiansen, Ed Melanson, Wendy M Kohrt, Martina Mancini, Deborah Josbeno, Katherine Balfany, Garett Griffith, Mac Kenzie Dunlap, Guillaume Lamotte, Erin Suttman, Danielle Larson, Chantale Branson, Kathleen E McKee, Li Goelz, Cynthia Poon, Barbara Tilley, Un Jung Kang, Malú Gámez Tansey, Nijee Luthra, Caroline M Tanner, Jacob M Haus, Giamila Fantuzzi, Nikolaus R McFarland, Paulina Gonzalez-Latapi, Tatiana Foroud, Robert Motl, Michael A Schwarzschild, Tanya Simuni, Kenneth Marek, Anna Naito, Codrin Lungu, Daniel M Corcos, SPARX3-PSG Investigators, Terry D Ellis, Ludy C Shih, Timothy J Nordahl, Michael T Stevenson, Jay L Alberts, Ashwini K Rao, Corey Landis, Joe R Nocera, Madeleine E Hackney, Elizabeth L Stegemoller, Angela L Ridgel, Jan M Hondzinski, Neil M Johannsen, Patrick Drummond, Heather Milton, David A Hinkle, Fay B Horak, Mitra Afshari, Christopher P Hurt, Ariel Kidwell, Corinna Conroy, Neil Panchal, Brooke Schultz, Jes Marchbank, Aaron Bloemer, Demetra D Christou, David E Vaillancourt, Stephanie Lapierre, Colum D MacKinnon, Sommer Amundsen-Huffmaster, Kristin Garland, Blake B Rasmussen, Summer Chapman, Jessica Spahn, Laura Wu, Lee E Dibble, Genevieve N Olivier, Art Weltman, William Alex Dalrymple, David Edwards, Corey Rynders, Lauren Miller, Gammon M Earhart, Kerri S Rawson, Kelvin Jones, Krista Nelles, Quincy J Almeida, Marie Saint-Hilaire, Stewart A Factor, Camilla Kilbane, Brian J Copeland, Marian L Dale, Alberto J Espay, Adolfo Ramirez-Zamora, Amanda Fessenden, Andres F Deik, Richard Camicioli, Charity G Patterson, Elizabeth Joslin, Alexandra B Gil, Wendy Spigle, Todd Nemet, Lana Chahine, Cory L Christiansen, Ed Melanson, Wendy M Kohrt, Martina Mancini, Deborah Josbeno, Katherine Balfany, Garett Griffith, Mac Kenzie Dunlap, Guillaume Lamotte, Erin Suttman, Danielle Larson, Chantale Branson, Kathleen E McKee, Li Goelz, Cynthia Poon, Barbara Tilley, Un Jung Kang, Malú Gámez Tansey, Nijee Luthra, Caroline M Tanner, Jacob M Haus, Giamila Fantuzzi, Nikolaus R McFarland, Paulina Gonzalez-Latapi, Tatiana Foroud, Robert Motl, Michael A Schwarzschild, Tanya Simuni, Kenneth Marek, Anna Naito, Codrin Lungu, Daniel M Corcos, SPARX3-PSG Investigators, Terry D Ellis, Ludy C Shih, Timothy J Nordahl, Michael T Stevenson, Jay L Alberts, Ashwini K Rao, Corey Landis, Joe R Nocera, Madeleine E Hackney, Elizabeth L Stegemoller, Angela L Ridgel, Jan M Hondzinski, Neil M Johannsen, Patrick Drummond, Heather Milton, David A Hinkle, Fay B Horak, Mitra Afshari, Christopher P Hurt, Ariel Kidwell, Corinna Conroy, Neil Panchal, Brooke Schultz, Jes Marchbank, Aaron Bloemer, Demetra D Christou, David E Vaillancourt, Stephanie Lapierre, Colum D MacKinnon, Sommer Amundsen-Huffmaster, Kristin Garland, Blake B Rasmussen, Summer Chapman, Jessica Spahn, Laura Wu, Lee E Dibble, Genevieve N Olivier, Art Weltman, William Alex Dalrymple, David Edwards, Corey Rynders, Lauren Miller, Gammon M Earhart, Kerri S Rawson, Kelvin Jones, Krista Nelles, Quincy J Almeida, Marie Saint-Hilaire, Stewart A Factor, Camilla Kilbane, Brian J Copeland, Marian L Dale, Alberto J Espay, Adolfo Ramirez-Zamora, Amanda Fessenden, Andres F Deik, Richard Camicioli

Abstract

Background: To date, no medication has slowed the progression of Parkinson's disease (PD). Preclinical, epidemiological, and experimental data on humans all support many benefits of endurance exercise among persons with PD. The key question is whether there is a definitive additional benefit of exercising at high intensity, in terms of slowing disease progression, beyond the well-documented benefit of endurance training on a treadmill for fitness, gait, and functional mobility. This study will determine the efficacy of high-intensity endurance exercise as first-line therapy for persons diagnosed with PD within 3 years, and untreated with symptomatic therapy at baseline.

Methods: This is a multicenter, randomized, evaluator-blinded study of endurance exercise training. The exercise intervention will be delivered by treadmill at 2 doses over 18 months: moderate intensity (4 days/week for 30 min per session at 60-65% maximum heart rate) and high intensity (4 days/week for 30 min per session at 80-85% maximum heart rate). We will randomize 370 participants and follow them at multiple time points for 24 months. The primary outcome is the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score (Part III) with the primary analysis assessing the change in MDS-UPDRS motor score (Part III) over 12 months, or until initiation of symptomatic antiparkinsonian treatment if before 12 months. Secondary outcomes are striatal dopamine transporter binding, 6-min walk distance, number of daily steps, cognitive function, physical fitness, quality of life, time to initiate dopaminergic medication, circulating levels of C-reactive protein (CRP), and brain-derived neurotrophic factor (BDNF). Tertiary outcomes are walking stride length and turning velocity.

Discussion: SPARX3 is a Phase 3 clinical trial designed to determine the efficacy of high-intensity, endurance treadmill exercise to slow the progression of PD as measured by the MDS-UPDRS motor score. Establishing whether high-intensity endurance treadmill exercise can slow the progression of PD would mark a significant breakthrough in treating PD. It would have a meaningful impact on the quality of life of people with PD, their caregivers and public health.

Trial registration: ClinicalTrials.gov NCT04284436 . Registered on February 25, 2020.

Keywords: Blood biomarkers; DaTscan™ SPECT; Endurance exercise; Exercise dose response; Gait assessment; Parkinson disease; Quality of life; Time to initiate dopaminergic medication; Treadmill exercise.

Conflict of interest statement

Oregon Health Sciences University (OHSU) and Dr. Horak have a significant financial interest in APDM Precision Motion, a division of Clario, International that may have a commercial interest in the results of this research and technology. This potential conflict has been reviewed and managed by OHSU. The other authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Design of the Study in Parkinson Disease of Exercise (SPARX3) Trial. The moderate-intensity exercise group is assigned to exercise 4 days a week at 60–65% HRmax, and the high-intensity exercise is assigned to exercise 4 days a week at 80–85% HRmax. The duration of the intervention is 18 months. Months 19 to 24 are observational

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