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

The SPARX3-PSG Investigators

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageEnglish (US)
Article number855
JournalTrials
Volume23
Issue number1
DOIs
StatePublished - Dec 2022

Funding

Funding for the SPARX3 trial is provided by NINDS grant number U01 NS113851. NINDS had no role in the original design of the study. With input from NINDS, the original study design was extended from 12 to 24 months of follow-up which includes 6 months of additional exercise intervention and 6 months follow-up. NINDS had no role in the writing of this manuscript. Research reported in this publication was also supported, in part, by the National Institutes of Health’s National Center for Advancing Translational Sciences, Grant Number UL1TR001422. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We would like to acknowledge the valuable role played by the DSMB in SPARX3. Their role in monitoring data and safety, as well as making suggestions for protocol modifications, has improved the implementation of SPARX3 significantly. The DSMB is comprised of Ellen Rosenberg, Eric Macklin, PhD, Sarah Pirio Richardson, MD, Michele Tagliati, MD, Nahab Fatta, MD, Lynne T. Braun, PhD, Jill Kanaley, PhD, and Judy Davidson, DNP. We would also like to acknowledge the valuable role played by Ergun Y. Uc, MD, from the University of Iowa as the Independent Medical Safety Monitor of SPARX3. Group authorship SPARX3 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 PSG 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

Keywords

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

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology (medical)

Fingerprint

Dive into the research topics of 'Study in Parkinson’s disease of exercise phase 3 (SPARX3): study protocol for a randomized controlled trial'. Together they form a unique fingerprint.

Cite this