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

• Authors: Joe Nocera, Emory University; Madeleine Hackney, Emory University; MariadeLourdes Tansey, Emory University; Stewart Factor, Emory University; CG Patterson, University of Pittsburgh; E Joslin, Northwestern University Feinberg School of Medicine; AB Gil, University of Pittsburgh; W Spigle, University of Pittsburgh; T Nemet, University of Pittsburgh; L Chahine, University of Pittsburgh School of Medicine; CL Christiansen, University of Colorado School of Medicine; E Melanson, University of Colorado Anschutz Medical Campus; WM Kohrt, University of Colorado Anschutz Medical Campus; M Mancini, OHSU School of Medicine; D Josbeno, University of Pittsburgh; K Balfany, University of Colorado School of Medicine; G Griffith, Northwestern University Feinberg School of Medicine; MK Dunlap, Cleveland Clinic Foundation; G Lamotte, University of Utah School of Medicine; E Suttman, The University of Utah; D Larson, Northwestern University Feinberg School of Medicine; C Branson, Morehouse School of Medicine; KE McKee, Intermountain Healthcare; L Goelz, University of Illinois at Chicago; C Poon, Northwestern University Feinberg School of Medicine; B Tilley, University of Texas School of Public Health; UJ Kang, NYU Grossman School of Medicine; N Luthra, University of California, San Francisco; CM Tanner, University of California, San Francisco; JM Haus, University of Michigan, Ann Arbor; G Fantuzzi, University of Illinois at Chicago; NR McFarland, University of Florida College of Medicine; P Gonzalez-Latapi, Northwestern University Feinberg School of Medicine; T Foroud, Indiana University School of Medicine; R Motl, University of Illinois at Chicago; MA Schwarzschild, Massachusetts General Hospital; T Simuni, Northwestern University Feinberg School of Medicine; K Marek, Institute for Neurodegenerative Disorders; A Naito, Parkinson’s Foundation 200 SE 1st Street Suite 800; C Lungu, National Institute of Neurological Disorders and Stroke (NINDS); DM Corcos, Northwestern University Feinberg School of Medicine; TD Ellis; LC Shih; TJ Nordahl; MT Stevenson; JL Alberts; AK Rao; C Landis; EL Stegemoller; AL Ridgel; JM Hondzinski; NM Johannsen; P Drummond; H Milton; DA Hinkle; FB Horak; M Afshari; CP Hurt; A Kidwell; C Conroy; N Panchal; B Schultz; J Marchbank; A Bloemer; DD Christou; DE Vaillancourt; S Lapierre; CD MacKinnon; S Amundsen-Huffmaster; K Garland; BB Rasmussen; S Chapman; J Spahn; L Wu; LE Dibble; GN Olivier; A Weltman; WA Dalrymple; D Edwards; C Rynders; L Miller; GM Earhart; KS Rawson; K Jones; K Nelles; QJ Almeida; M Saint-Hilaire; C Kilbane; BJ Copeland; ML Dale; AJ Espay; A Ramirez-Zamora; A Fessenden; AF Deik; R Camicioli
• Journal Title: Trials
• Volume: Volume 23, Number 1
• Publisher: (publisher) | 2022-12-01, Pages 855-855
• Type of Work: Article
• Publisher DOI: http://doi.org/10.1186/s13063-022-06703-0
• Keywords: Blood biomarkers; DaTscan™ SPECT; Endurance exercise; Exercise dose response; Gait assessment; Parkinson disease; Quality of life; Time to initiate dopaminergic medication; Treadmill exercise; Antiparkinson Agents; Brain-Derived Neurotrophic Factor; C-Reactive Protein; Clinical Trials, Phase III as Topic; Dopamine Plasma Membrane Transport Proteins; Exercise; Exercise Therapy; Humans; Multicenter Studies as Topic; Parkinson Disease; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome

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.govNCT04284436. Registered on February 25, 2020.