Active, not recruitingNCT04284436SPARX3Updated Jul 10, 2026

Study in Parkinson Disease of Exercise

An interventional study of Treadmill walking in Parkinson Disease, sponsored by Northwestern University. Active, not recruiting at 25 sites in 2 countries. Open to participants aged 40 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-07-10.

Sponsored by Northwestern University · Not applicable, Interventional, and Treatment

Phase: Not applicable
Study type: Interventional
Enrollment: 370
Allocation: Randomized
Ages: 40 Years to 80 Years
Sex: All

Study summary

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.

Read the 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.

Conditions studied

Parkinson Disease

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Parkinson Disease 4,487

In context

Parkinson Disease

4,487 studies on the registry are indexed under Parkinson Disease; 1,082 are open to participants now.

This study's enrollment of 370 is above the median of 40 across 3,294 interventional studies indexed under Parkinson Disease.

Browse Parkinson Disease studies →

Lead sponsor

Northwestern University is the lead sponsor of 1,396 studies on the registry; 199 are open to participants now.

Of its 102 completed or terminated interventional studies of FDA-regulated products, 73 (72%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 40 Years to 80 Years
Sexes eligible: All
Accepts healthy volunteers: No

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

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 design

Phase: Not applicable
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Single (Outcomes assessor)
Enrollment: 370 participants (actual)

Study arms

Experimental
High Intensity Exercise
Treadmill exercise 4x per week at 80-85% HRmax.
Behavioral: Treadmill walking
Active comparator
Moderate Intensity Exercise
Treadmill exercise 4x per week at 60-65% HRmax.
Behavioral: Treadmill walking

Interventions

BehavioralTreadmill walking
Treadmill walking 4 days per week for 30 minutes in the target heart rate

What researchers measure

Primary outcomes

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.
Time frame: 12 months

Secondary outcomes

Change in dopaminergic activity
Change from baseline in the striatal specific binding ratio (SSBR) as measured by dopamine transporter imaging
Time frame: 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.
Time frame: 18 months
Change in walking capacity
Change from baseline in distance in 6-minute walk
Time frame: 12 months
Change in walking capacity
Change from baseline in distance in 6-minute walk
Time frame: 18 months
Change in activity
Change from baseline in the number of steps
Time frame: 12 months
Change in activity
Change from baseline in the number of steps
Time frame: 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.
Time frame: 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.
Time frame: 18 months
Change in fitness
Change from baseline in maximal oxygen consumption measured with peak oxygen volume
Time frame: 12 months
Change in fitness
Change from baseline in maximal oxygen consumption measured with peak oxygen volume
Time frame: 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.
Time frame: 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.
Time frame: 18 months
Initiation of dopaminergic therapy
Time to initiation of dopaminergic therapy
Time frame: 12 months
Change in blood derived marker of inflammation
Change from baseline in C-reactive protein
Time frame: 12 months
Change in blood derived marker of inflammation
Change from baseline in C-reactive protein
Time frame: 18 months
Change in blood derived marker of neuronal development
Change from baseline in brain derived neurotrophic factor (BDNF)
Time frame: 12 months
Change in blood derived marker of neuronal development
Change from baseline in brain derived neurotrophic factor (BDNF)
Time frame: 18 months

Other outcomes

Change in stride length
Change in stride length assessed using OPAL movement monitors during the 6 minute walk test
Time frame: 12 months
Change in stride length
Change in stride length assessed using OPAL movement monitors during the 6 minute walk test
Time frame: 18 months
Change in turning velocity
Change in turning velocity assessed using OPAL movement monitors during the 6 minute walk test
Time frame: 12 months
Change in turning velocity
Change in turning velocity assessed using OPAL movement monitors during the 6 minute walk test
Time frame: 18 months

Study locations

25 sites

University of Alabama at Birmingham
Birmingham, Alabama 35294, United States
University of California, San Francisco
San Francisco, California 94143, United States
University of Colorado, Denver
Aurora, Colorado 80204, United States
University of Florida
Gainesville, Florida 32611, United States
Morehouse School of Medicine
Atlanta, Georgia 30310, United States
Emory University
Atlanta, Georgia 30322, United States
Northwestern University
Chicago, Illinois 60611, United States
Rush University Medical Center
Chicago, Illinois 60612, United States
Iowa State University
Ames, Iowa 50011, United States
Louisiana State University
Baton Rouge, Louisiana 70803, United States
Boston University (Charles River Campus)
Boston, Massachusetts 02215, United States
University of Michigan
Ann Arbor, Michigan 48109, United States
University of Minnesota
Minneapolis, Minnesota 55455, United States
Washington University St. Louis
St Louis, Missouri 63130, United States
Columbia University Medical Center
New York, New York 10032, United States
University of Cincinnati
Cincinnati, Ohio 45221, United States
Cleveland Clinic
Cleveland, Ohio 44195, United States
Ohio Health
Columbus, Ohio 43214, United States
Kent State University
Kent, Ohio 44240, United States
Oregon Health & Science University
Portland, Oregon 97239, United States
University of Pennsylvania
Philadelphia, Pennsylvania 19104, United States
University of Pittsburgh
Pittsburgh, Pennsylvania 15219, United States
UT Health San Antonio
San Antonio, Texas 78229, United States
University of Utah
Salt Lake City, Utah 84112, United States
University of Alberta
Edmonton, Canada

References and documents

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. PubMed 29228079 ↗
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. PubMed 23770108 ↗
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. PubMed 36203214 ↗

Study documents

Informed consent form · Jun 2, 2025

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — All study data (deidentified) and documentation will be shared with the National Institute of Neurological Disease and Stroke.

Supporting information: Study protocol, Sap, Icf, Csr, Analytic code

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jul 10, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT04284436
Lead sponsor: Northwestern University
Collaborators: University of Pittsburgh, The Parkinson Study Group
Responsible party: Daniel Corcos (Professor of Physical Therapy and Human Movement Sciences, Northwestern University) — Principal investigator
First posted: Feb 25, 2020
Start date: Aug 30, 2021
Primary completion: Jul 31, 2027 (estimated)
Completion: Jul 31, 2028 (estimated)
Last update: Jul 10, 2026

Study contacts

Daniel M Corcos, PhD

principal investigator · Northwestern University

Oversight

Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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This study is active, not recruiting, as verified in Apr 2026. You cannot join it, but the record below documents what was studied.

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