Clinical trial NCT04284436: Study in Parkinson Disease of Exercise
Official title: Study in Parkinson Disease of Exercise Phase 3 Clinical Trial: SPARX3
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Parkinson Disease
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: University of Pittsburgh
name: The Parkinson Study Group
First posted: 2020-02-25
Enrollment: 370
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

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).

Primary outcomes:
measure: Change in motor symptoms of Parkinson disease
timeFrame: 12 months
Secondary outcomes:
measure: Change in dopaminergic activity
timeFrame: 12 months
measure: Change in motor symptoms of Parkinson disease
timeFrame: 18 months
measure: Change in walking capacity
timeFrame: 12 months
measure: Change in walking capacity
timeFrame: 18 months
measure: Change in activity
timeFrame: 12 months
measure: Change in activity
timeFrame: 18 months
measure: Change in cognitive function
timeFrame: 12 months
measure: Change in cognitive function
timeFrame: 18 months
measure: Change in fitness
timeFrame: 12 months
measure: Change in fitness
timeFrame: 18 months
measure: Change in quality of life
timeFrame: 12 months
measure: Change in quality of life
timeFrame: 18 months
measure: Initiation of dopaminergic therapy
timeFrame: 12 months
measure: Change in blood derived marker of inflammation
timeFrame: 12 months
measure: Change in blood derived marker of inflammation
timeFrame: 18 months
measure: Change in blood derived marker of neuronal development
timeFrame: 12 months
measure: Change in blood derived marker of neuronal development
timeFrame: 18 months
Other outcomes:
measure: Change in stride length
timeFrame: 12 months
measure: Change in stride length
timeFrame: 18 months
measure: Change in turning velocity
timeFrame: 12 months
measure: Change in turning velocity
timeFrame: 18 months
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado, Denver
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Atlanta
country: United States
facility: Morehouse School of Medicine
state: Georgia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Ames
country: United States
facility: Iowa State University
state: Iowa
city: Baton Rouge
country: United States
facility: Louisiana State University
state: Louisiana
city: Boston
country: United States
facility: Boston University (Charles River Campus)
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University St. Louis
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio Health
state: Ohio
city: Kent
country: United States
facility: Kent State University
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: San Antonio
country: United States
facility: UT Health San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Edmonton
country: Canada
facility: University of Alberta
Study officials:
affiliation: Northwestern University
name: Daniel M Corcos, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.