Study in Parkinson Disease of Exercise (SPARX3)

Study in Parkinson Disease of Exercise Phase 3 Clinical Trial: SPARX3

This study is a Phase 3 multi-site, randomized, evaluator-masked, study of endurance treadmill exercise on changes in the Movement Disorder Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS) Part III score at 12 months among persons with early stage Parkinson disease. 370 participants will be randomly assigned to 2 groups: 1)60-65% HRmax or 2)80-85% HRmax 4 times per week. The primary objective is to test whether the progression of the signs of Parkinson's disease is attenuated at 12 months in among persons who have not initiated medication for Parkinson Disease (PD) when they perform high-intensity endurance treadmill exercise.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Behavioral: Treadmill walking

Detailed Description

This study is a Phase 3 multi-site, randomized, evaluator-masked, study of endurance treadmill exercise on changes in the MDS-UPDRS Part III score at 12 months. 370 persons diagnosed with Parkinson's disease who have not yet initiated dopaminergic therapy, age 40-80, will be randomly assigned to 2 groups: 1)60-65% HRmax or 2)80-85% HRmax 4 times per week. Secondary objectives will test hypotheses related to striatal specific binding ratio (SSBR) at 12 months, MDS-UPDRS Part III score, ambulatory mobility (6-minute walk), daily walking activity (steps), cognition, quality of life, cardiorespiratory fitness, blood-derived biomarkers of inflammation and neurotrophic factors at 12 and 18 months. Tertiary objectives will test hypotheses related to 2 characteristics of ambulation at 12 and 18 months. Exploratory objectives will test hypotheses related to the effects of removing the study support that was provided over 18 months on the sustainability and durability of the exercise effects at 24 months. Approximately 29 sites will enroll participants: 27 sites that cover all geographic regions of the USA and 2 sites in Canada. All sites will have a collaboration between movement disorders and exercise specialists.

• Study Type: Interventional
• Enrollment (Estimated): 370
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Elizabeth Joslin; Phone Number: 309-922-7254; Email: elizabeth.joslin@northwestern.edu

Study Locations

• Canada
  • Edmonton, Canada
    • Recruiting
    • University of Alberta
    • Contact: Krista Nelles; Phone Number: 780-248-2043
    • Principal Investigator: Richard Camicioli, MD
    • Principal Investigator: Kelvin Jones, PhD
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Recruiting
      • University of Alabama at Birmingham
      • Principal Investigator: Christopher Hurt, PhD
      • Contact: Sarah Bruton; Phone Number: 678-200-0624; Email: sbruton@uab.edu
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California, San Francisco
      • Contact: Corinna Conroy; Phone Number: 415-502-2960; Email: corinna.conroy@ucsf.edu
      • Principal Investigator: Carlie Tanner
      • Principal Investigator: Nijee Luthra
  • Colorado
    • Aurora, Colorado, United States, 80204
      • Recruiting
      • University of Colorado, Denver
      • Contact: Katherine Balfany; Phone Number: 303-724-9101; Email: SPARX3@ucdenver.edu
      • Principal Investigator: Cory Christiansen, PhD
  • Florida
    • Gainesville, Florida, United States, 32611
      • Recruiting
      • University of Florida
      • Contact: Amanda Fessenden; Phone Number: 352-733-2421; Email: amanda.fessenden@neurology.ufl.edu
      • Principal Investigator: Demetra Christou, PhD
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University
      • Contact: Joe Nocera, PhD; Phone Number: 206354 404-321-6111; Email: joenocera@emory.edu
      • Principal Investigator: Joe Nocera, PhD
    • Atlanta, Georgia, United States, 30310
      • Recruiting
      • Morehouse School Of Medicine
      • Contact: Paula Phabian-Millbrook; Phone Number: 404-756-5053; Email: parkinsonstudy@msm.edu
      • Principal Investigator: Chantale Branson, MD
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • Rush University Medical Center
      • Principal Investigator: Mitra Afshari, MD
      • Contact: Jacob Hawkins; Phone Number: 651-492-3944; Email: jacob_hawkins@rush.edu
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
      • Contact: Garett Griffith; Phone Number: 708-703-2591; Email: garett.griffith@northwestern.edu
      • Principal Investigator: Cynthia Poon, PhD
  • Iowa
    • Ames, Iowa, United States, 50011
      • Recruiting
      • Iowa State University
      • Contact: Elizabeth Stegemoller, PhD; Phone Number: 515-294-5966; Email: esteg@iastate.edu
      • Principal Investigator: Elizabeth Stegemoller, PhD
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70803
      • Recruiting
      • Louisiana State University
      • Contact: Jan Hondzinski, PhD; Phone Number: 225-578-9144; Email: jhondz1@lsu.edu
      • Principal Investigator: Jan Hondzinski, PhD
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Boston University (Charles River Campus)
      • Contact: Michael Stevenson; Phone Number: 617-638-7747; Email: msteven1@bu.edu
      • Principal Investigator: Terry Ellis, PhD
      • Principal Investigator: Ludy Shih, MD
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
      • Contact: Jacob Haus, PhD; Phone Number: 734-647-2790; Email: jmhaus@umich.edu
      • Principal Investigator: Jacob Haus, PhD
      • Contact: Jake Fogel; Phone Number: 631-356-9361; Email: jafogel@umich.edu
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota
      • Contact: Kristin Garland; Email: garl0038@umn.edu
      • Principal Investigator: Colum MacKinnon, PhD
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Recruiting
      • Washington University St. Louis
      • Contact: Martha Hessler; Phone Number: 314-286-1478; Email: mjhessler@wustl.edu
      • Principal Investigator: Gammon Earhart, PhD
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
      • Principal Investigator: Ashwini Rao, EdD
      • Contact: Corey Landis; Phone Number: 212-305-1647; Email: cl4129@cumc.columbia.edu
  • Ohio
    • Cincinnati, Ohio, United States, 45221
      • Recruiting
      • University of Cincinnati
      • Contact: Jessica Marchbank; Phone Number: 513-558-4811; Email: jessica.doak@uc.edu
      • Principal Investigator: Alberto Espay, MD
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Contact: MacKenzie Dunlap; Phone Number: 216-444-7474; Email: sparx@ccf.org
      • Principal Investigator: Jay Alberts, PhD
    • Columbus, Ohio, United States, 43214
      • Recruiting
      • Ohio Health
      • Contact: Kitra Hunter; Phone Number: 614-566-1262; Email: kitra.hunter@ohiohealth.com
      • Principal Investigator: David Hinkle
    • Kent, Ohio, United States, 44240
      • Recruiting
      • Kent State University
      • Contact: Eileen Terrell; Phone Number: 216-844-2328; Email: eileen.terrell@UHHospitals.org
      • Principal Investigator: Angela Ridgel, PhD
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
      • Principal Investigator: Martina Mancini, PhD
      • Contact: Ashlynn Lawson; Phone Number: 503-418-2601; Email: lawston@ohsu.edu
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Contact: Marcela Pavon; Phone Number: 215-829-7725; Email: Marcela.Pavon@pennmedicine.upenn.edu
      • Contact: Whitney Hartstone; Phone Number: 215-829-7725; Email: whitney.hartstone@pennmedicine.upenn.edu
      • Principal Investigator: Andres Diek Acost Madiedo, MD
    • Pittsburgh, Pennsylvania, United States, 15219
      • Recruiting
      • University of Pittsburgh
      • Contact: Kathleen Betts; Phone Number: 412-443-8079; Email: kmb251@pitt.edu
      • Principal Investigator: Deborah Josbeno, PhD
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Recruiting
      • University of Utah
      • Contact: Genevieve "G" Olivier; Phone Number: 801-587-3181; Email: g.olivier@utah.edu
      • Contact: Erin Suttman; Phone Number: 801-587-3181; Email: erin.suttman@utah.edu
      • Principal Investigator: Lee Dibble, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• A diagnosis of idiopathic Parkinson Disease based on the modified * United Kingdom (UK) PD brain bank criteria and which are consistent with recent criteria proposed for clinically established early established Parkinson's disease that no longer exclude individuals with a family history of Parkinson's disease.
• Hoehn and Yahr stages less than 3
• Disease duration: less than 3 years since disease diagnosis
• Age 40-80 years
• Positive DaTscan™ SPECT by quantitative readout for idiopathic Parkinson disease.

Exclusion Criteria:

• Currently being treated with PD medications such as levodopa or dopamine receptor agonists, monoamine oxidase-B (MAO-B) inhibitors, amantadine, or anticholinergics.
• Expected to require treatment with medication for PD in the first 6 months of the study.
• Use of any PD medication 60 days prior to the baseline visit including but not limited to levodopa, direct dopamine agonists, amantadine, Rasagiline (Azilect), Selegiline (Eldepryl), Artane (trihexyphenidyl).
• Duration of previous use of medications for PD exceeds 60 days.
• Use of neuroleptics/dopamine receptor blockers for more than 30 days in the year prior to baseline visit, or any use within 30 days of baseline visit
• Presence of known cardiovascular, metabolic, or renal disease or individuals with major signs or symptoms suggestive of cardiovascular, metabolic, or renal disease without medical clearance to participate in the exercise program.
• Uncontrolled hypertension (resting blood pressure >150/90 mmHg)
• Individuals with orthostatic hypotension and standing systolic BP below 100 will be excluded. Orthostatic hypotension (OH) is a reduction of systolic blood pressure of at least 20 mm Hg or diastolic blood pressure of at least 10 mm Hg within 3 minutes of standing.
• Hypo- or hyperthyroidism (TSH <0.5 or >5.0 mU/L), abnormal liver function (AST or ALT more than 2 times the upper limit of normal), abnormal renal function (estimated glomerular filtration rate (eGFR) using the MDRD4 equation or the CKD-EPI equation <45mL/min/1.73m2 ).
• Complete Blood Count (CBC) out of range and physician's judgment that abnormal value is clinically significant.
• Recent use of psychotropic medications (e.g., anxiolytics, hypnotics, benzodiazepines, antidepressants) where dosage has not been stable for 28 days prior to screening.
• Serious illness (requiring systemic treatment and/or hospitalization) within the last 4 weeks.
• Any other clinically significant medical condition, psychiatric condition, drug or alcohol abuse, assessment or laboratory abnormality that would, in the judgment of the investigator, interfere with the subject's ability to participate in the study.
• Montreal Cognitive Assessment (MoCA) score of <24.
• Beck Depression Inventory II (BDI) score > 28, indicating severe depression that precludes ability to exercise. Any subject with such a score will be referred to a PCP or physician for further evaluation and management of depression. Individuals with a BDI-II score of 17-28 will be excluded if any of the following conditions are met: (1) individual is suicidal, (2) is in need of depression treatment modification currently or (3) depressive symptoms likely to interfere with adherence to study protocol. Any subject with such a score will be referred to a PCP or physician for further evaluation and management of depression.
• Individuals who have been exercising at greater than moderate intensity for 120 minutes or more per week consistently over the last 6 months will be excluded. Greater than moderate intensity is defined as a range greater than 60-65% HRmax. These individuals are excluded since their exercise activities are greater than the activities they would experience if they were assigned to the 60-65% treatment group. As such, they would be expected to lose fitness.
• Use of the following within 90 days prior to the DAT neuroimaging screening evaluation: modafinil, armodafinil, metoclopramide, alpha-methyldopa, methylphenidate, reserpine, any amphetamine or amphetamine derivative, or use of buproprion within 8 days prior to the DAT neuroimaging screening evaluation. These can compromise DaTscan™ SPECT.
• Known allergy to iodinated products.
• Known hypersensitivity to DaTscan™ SPECT (either to the active substance of 123I-ioflupane or any of the excipients.
• (For women only) Actively breast-feeding an infant, and/or pregnant, or plan to become pregnant in the next 12 months.
• Other disorders, injuries, diseases, or conditions that might interfere with ability to perform endurance exercises (e.g. history of stroke, respiratory problems, traumatic brain injury, orthopedic injury, or neuromuscular disease).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High Intensity Exercise; Treadmill exercise 4x per week at 80-85% HRmax.	Behavioral: Treadmill walking; Treadmill walking 4 days per week for 30 minutes in the target heart rate
Active Comparator: Moderate Intensity Exercise; Treadmill exercise 4x per week at 60-65% HRmax.	Behavioral: Treadmill walking; Treadmill walking 4 days per week for 30 minutes in the target heart rate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in motor symptoms of Parkinson disease	Change from baseline in the Movement Disorders Society-Unified Parkinson Disease Rating Scale motor score (Part III). The minimum score on the MDS-UPDRS Part III is 0 and the maximum is 132 with higher scores representing worse motor symptoms.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in dopaminergic activity	Change from baseline in the striatal specific binding ratio (SSBR) as measured by dopamine transporter imaging	12 months
Change in motor symptoms of Parkinson disease	Change from baseline in the Movement Disorders Society-Unified Parkinson Disease Rating Scale motor score (Part III). The minimum score on the MDS-UPDRS Part III is 0 and the maximum is 132 with higher scores representing worse motor symptoms.	18 months
Change in walking capacity	Change from baseline in distance in 6-minute walk	12 months
Change in walking capacity	Change from baseline in distance in 6-minute walk	18 months
Change in activity	Change from baseline in the number of steps	12 months
Change in activity	Change from baseline in the number of steps	18 months
Change in cognitive function	Change from baseline in the Montreal Cognitive Assessment (MoCA). MoCA scores range between 0 and 30, with higher scores representing a better outcome.	12 months
Change in cognitive function	Change from baseline in the Montreal Cognitive Assessment (MoCA). MoCA scores range between 0 and 30, with higher scores representing a better outcome.	18 months
Change in fitness	Change from baseline in maximal oxygen consumption measured with peak oxygen volume	12 months
Change in fitness	Change from baseline in maximal oxygen consumption measured with peak oxygen volume	18 months
Change in quality of life	Change from baseline in quality of life measured with the Parkinson Disease Questionnaire-39. The PDQ-39 is a 39-item self-report questionnaire, which assesses Parkinson's disease-specific health related quality over the last month covering 8 dimensions scored on a 5 point ordinal system (0=never, 4=always). Dimension score = sum of scores of each item in the dimension divided by the maximum possible score of all the items in the dimension, multiplied by 100. Each dimension total score range from 0 (never have difficulty) to 100 (always have difficulty). Lower scores reflect better QoL. Overall score can be summarized in the Parkinson's Disease Summary Index (PDSI) or PDQ-39 Summary Index (PDQ-39 SI).PDSI or PDQ-39 SI = sum of dimension total scores divided by 8.	12 months
Change in quality of life	Change from baseline in quality of life measured with the Parkinson Disease Questionnaire-39. The PDQ-39 is a 39-item self-report questionnaire, which assesses Parkinson's disease-specific health related quality over the last month covering 8 dimensions scored on a 5 point ordinal system (0=never, 4=always). Dimension score = sum of scores of each item in the dimension divided by the maximum possible score of all the items in the dimension, multiplied by 100. Each dimension total score range from 0 (never have difficulty) to 100 (always have difficulty). Lower scores reflect better QoL. Overall score can be summarized in the Parkinson's Disease Summary Index (PDSI) or PDQ-39 Summary Index (PDQ-39 SI).PDSI or PDQ-39 SI = sum of dimension total scores divided by 8.	18 months
Initiation of dopaminergic therapy	Time to initiation of dopaminergic therapy	12 months
Change in blood derived marker of inflammation	Change from baseline in C-reactive protein	12 months
Change in blood derived marker of inflammation	Change from baseline in C-reactive protein	18 months
Change in blood derived marker of neuronal development	Change from baseline in brain derived neurotrophic factor (BDNF)	12 months
Change in blood derived marker of neuronal development	Change from baseline in brain derived neurotrophic factor (BDNF)	18 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in stride length	Change in stride length assessed using OPAL movement monitors during the 6 minute walk test	12 months
Change in stride length	Change in stride length assessed using OPAL movement monitors during the 6 minute walk test	18 months
Change in turning velocity	Change in turning velocity assessed using OPAL movement monitors during the 6 minute walk test	12 months
Change in turning velocity	Change in turning velocity assessed using OPAL movement monitors during the 6 minute walk test	18 months

Collaborators and Investigators

• Sponsor: Northwestern University
• Collaborators: University of Pittsburgh; The Parkinson Study Group
• Investigators: Principal Investigator: Daniel M Corcos, PhD, Northwestern University

Publications and helpful links

General Publications

• Schenkman M, Moore CG, Kohrt WM, Hall DA, Delitto A, Comella CL, Josbeno DA, Christiansen CL, Berman BD, Kluger BM, Melanson EL, Jain S, Robichaud JA, Poon C, Corcos DM. Effect of High-Intensity Treadmill Exercise on Motor Symptoms in Patients With De Novo Parkinson Disease: A Phase 2 Randomized Clinical Trial. JAMA Neurol. 2018 Feb 1;75(2):219-226. doi: 10.1001/jamaneurol.2017.3517.
• Moore CG, Schenkman M, Kohrt WM, Delitto A, Hall DA, Corcos D. Study in Parkinson disease of exercise (SPARX): translating high-intensity exercise from animals to humans. Contemp Clin Trials. 2013 Sep;36(1):90-8. doi: 10.1016/j.cct.2013.06.002. Epub 2013 Jun 14.
• Patterson CG, Joslin E, Gil AB, Spigle W, Nemet T, Chahine L, Christiansen CL, Melanson E, Kohrt WM, Mancini M, Josbeno D, Balfany K, Griffith G, Dunlap MK, Lamotte G, Suttman E, Larson D, Branson C, McKee KE, Goelz L, Poon C, Tilley B, Kang UJ, Tansey MG, Luthra N, Tanner CM, Haus JM, Fantuzzi G, McFarland NR, Gonzalez-Latapi P, Foroud T, Motl R, Schwarzschild MA, Simuni T, Marek K, Naito A, Lungu C, Corcos DM; SPARX3-PSG Investigators. Study in Parkinson's disease of exercise phase 3 (SPARX3): study protocol for a randomized controlled trial. Trials. 2022 Oct 6;23(1):855. doi: 10.1186/s13063-022-06703-0.

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2021
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2028

Study Registration Dates

• First Submitted: February 20, 2020
• First Submitted That Met QC Criteria: February 21, 2020
• First Posted (Actual): February 25, 2020

Study Record Updates

• Last Update Posted (Actual): February 22, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: 1U01NS113851-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All study data (deidentified) and documentation will be shared with the National Institute of Neurological Disease and Stroke.
• IPD Sharing Time Frame: 18 months after the study end.
• IPD Sharing Access Criteria: Once the data are in the NINDS data repository, NINDS will be responsible for determining with whom the data are shared. No data will be shared directly from the study data coordinating center.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No