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Study in Parkinson Disease of Exercise (SPARX3)

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ClinicalTrials.gov Identifier: NCT04284436
Recruitment Status : Recruiting
First Posted : February 25, 2020
Last Update Posted : April 23, 2021
Sponsor:
Collaborator:
University of Pittsburgh
Information provided by (Responsible Party):
Daniel Corcos, Northwestern University

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.

Condition or disease Intervention/treatment Phase
Parkinson Disease Behavioral: Treadmill walking Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 370 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Study in Parkinson Disease of Exercise Phase 3 Clinical Trial: SPARX3
Actual Study Start Date : March 19, 2021
Estimated Primary Completion Date : July 31, 2025
Estimated Study Completion Date : July 31, 2025

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Change in motor symptoms of Parkinson disease [ Time Frame: 12 months ]
    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.


Secondary Outcome Measures :
  1. Change in dopaminergic activity [ Time Frame: 12 months ]
    Change from baseline in the striatal specific binding ratio (SSBR) as measured by dopamine transporter imaging

  2. Change in motor symptoms of Parkinson disease [ Time Frame: 18 months ]
    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.

  3. Change in walking capacity [ Time Frame: 12 months ]
    Change from baseline in distance in 6-minute walk

  4. Change in walking capacity [ Time Frame: 18 months ]
    Change from baseline in distance in 6-minute walk

  5. Change in activity [ Time Frame: 12 months ]
    Change from baseline in the number of steps

  6. Change in activity [ Time Frame: 18 months ]
    Change from baseline in the number of steps

  7. Change in cognitive function [ Time Frame: 12 months ]
    Change from baseline in the Montreal Cognitive Assessment (MoCA). MoCA scores range between 0 and 30, with higher scores representing a better outcome.

  8. Change in cognitive function [ Time Frame: 18 months ]
    Change from baseline in the Montreal Cognitive Assessment (MoCA). MoCA scores range between 0 and 30, with higher scores representing a better outcome.

  9. Change in fitness [ Time Frame: 12 months ]
    Change from baseline in maximal oxygen consumption measured with peak oxygen volume

  10. Change in fitness [ Time Frame: 18 months ]
    Change from baseline in maximal oxygen consumption measured with peak oxygen volume

  11. Change in quality of life [ Time Frame: 12 months ]
    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. Change in quality of life [ Time Frame: 18 months ]
    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.

  13. Initiation of dopaminergic therapy [ Time Frame: 12 months ]
    Time to initiation of dopaminergic therapy

  14. Change in blood derived marker of inflammation [ Time Frame: 12 months ]
    Change from baseline in C-reactive protein

  15. Change in blood derived marker of inflammation [ Time Frame: 18 months ]
    Change from baseline in C-reactive protein

  16. Change in blood derived marker of neuronal development [ Time Frame: 12 months ]
    Change from baseline in brain derived neurotrophic factor (BDNF)

  17. Change in blood derived marker of neuronal development [ Time Frame: 18 months ]
    Change from baseline in brain derived neurotrophic factor (BDNF)


Other Outcome Measures:
  1. Change in stride length [ Time Frame: 12 months ]
    Change in stride length assessed using OPAL movement monitors during the 6 minute walk test

  2. Change in stride length [ Time Frame: 18 months ]
    Change in stride length assessed using OPAL movement monitors during the 6 minute walk test

  3. Change in turning velocity [ Time Frame: 12 months ]
    Change in turning velocity assessed using OPAL movement monitors during the 6 minute walk test

  4. Change in turning velocity [ Time Frame: 18 months ]
    Change in turning velocity assessed using OPAL movement monitors during the 6 minute walk test



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   40 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 30 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 (creatinine clearance calculated by the Cockcroft-Gault equation <50mL/min, or estimated glomerular filtration rate 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 <26 to rule out mild cognitive impairment (MCI).
  • Beck Depression Inventory II (BDI) score > 16, indicating depression that precludes ability to exercise. Any subject with such a score will be referred to a primary care physician (PCP) or physician for further evaluation and management of depression.
  • Individuals participating in 120 minutes or more of moderate intensity exercise per week within the last 6 months will be excluded. Moderate intensity is defined as a range greater than 60-65% HRmax. These individuals are excluded since their exercise activities are equal to or greater than the activities they would experience if they were assigned to the 60-65% treatment group.
  • Use of the following within 90 days prior to the dopamine transporter (DAT) neuroimaging screening evaluation: bupropion, modafinil, armodafinil, metoclopramide, alpha-methyldopa, methylphenidate, reserpine, any amphetamine or amphetamine derivative. 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.
  • Prior SPECT scan within 6 months of baseline scan. Recruitment will be delayed for individuals who have had a previous SPECT scan within 6 months of the baseline scan.
  • (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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04284436


Contacts
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Contact: Elizabeth Skender 309-922-7254 elizabeth.skender@northwestern.edu
Contact: Charity Patterson, PhD 412-383-4812 cgp22@pitt.edu

Locations
Show Show 29 study locations
Sponsors and Collaborators
Northwestern University
University of Pittsburgh
Investigators
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Principal Investigator: Daniel M Corcos, PhD Northwestern University
Publications:
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Responsible Party: Daniel Corcos, Professor of Physical Therapy and Human Movement Sciences, Northwestern University
ClinicalTrials.gov Identifier: NCT04284436    
Other Study ID Numbers: 1U01NS113851-01 ( U.S. NIH Grant/Contract )
First Posted: February 25, 2020    Key Record Dates
Last Update Posted: April 23, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All study data (deidentified) and documentation will be shared with the National Institute of Neurological Disease and Stroke.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: 18 months after the study end.
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.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases