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Study in Parkinson Disease of Exercise

NCT04284436 · Northwestern University
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Official title
Study in Parkinson Disease of Exercise Phase 3 Clinical Trial: SPARX3
About this study
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.
Eligibility criteria
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 design
Enrollment target: 370 participants
Allocation: randomized
Masking: single
Age groups: adult, older_adult
Timeline
Starts: 2021-08-30
Estimated completion: 2028-07-31
Last updated: 2026-04-13
Interventions
Behavioral: Treadmill walking
Primary outcomes
  • Change in motor symptoms of Parkinson disease (12 months)
Sponsor
Northwestern University · other
With: University of Pittsburgh, The Parkinson Study Group
Contacts & investigators
ContactElizabeth Joslin · contact · elizabeth.joslin@northwestern.edu · 309-922-7254
InvestigatorDaniel M Corcos, PhD · principal_investigator, Northwestern University
All locations (25)
University of Alabama at BirminghamRecruiting
Birmingham, Alabama, United States
University of California, San FranciscoRecruiting
San Francisco, California, United States
University of Colorado, DenverRecruiting
Aurora, Colorado, United States
University of FloridaRecruiting
Gainesville, Florida, United States
Morehouse School of MedicineActive Not Recruiting
Atlanta, Georgia, United States
Emory UniversityRecruiting
Atlanta, Georgia, United States
Northwestern UniversityRecruiting
Chicago, Illinois, United States
Rush University Medical CenterRecruiting
Chicago, Illinois, United States
Iowa State UniversityRecruiting
Ames, Iowa, United States
Louisiana State UniversityRecruiting
Baton Rouge, Louisiana, United States
Boston University (Charles River Campus)Recruiting
Boston, Massachusetts, United States
University of MichiganRecruiting
Ann Arbor, Michigan, United States
University of MinnesotaRecruiting
Minneapolis, Minnesota, United States
Washington University St. LouisRecruiting
St Louis, Missouri, United States
Columbia University Medical CenterRecruiting
New York, New York, United States
University of CincinnatiRecruiting
Cincinnati, Ohio, United States
Cleveland ClinicRecruiting
Cleveland, Ohio, United States
Ohio HealthRecruiting
Columbus, Ohio, United States
Kent State UniversityRecruiting
Kent, Ohio, United States
Oregon Health & Science UniversityRecruiting
Portland, Oregon, United States
University of PennsylvaniaRecruiting
Philadelphia, Pennsylvania, United States
University of PittsburghRecruiting
Pittsburgh, Pennsylvania, United States
UT Health San AntonioRecruiting
San Antonio, Texas, United States
University of UtahRecruiting
Salt Lake City, Utah, United States
University of AlbertaRecruiting
Edmonton, Canada
Study in Parkinson Disease of Exercise · TrialPath