SPARX3: Study in Parkinson Disease of Exercise

• Sponsor: Northwestern University (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04284436
• Collaborator: University of Pittsburgh (Other), The Parkinson Study Group (Other)
• Enrollment: 370
• Locations: 27
• Arms: 2
• Anticipated Duration (Months): 52.4
• Patients Per Site: 13.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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	N/A

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 Design

• Study Type: Interventional
• Anticipated 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: Mar 19, 2021
• Anticipated Primary Completion Date: Jul 31, 2025
• Anticipated Study Completion Date: Jul 31, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change in motor symptoms of Parkinson disease [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 [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 [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 [12 months]

   Change from baseline in distance in 6-minute walk

4. Change in walking capacity [18 months]

   Change from baseline in distance in 6-minute walk

5. Change in activity [12 months]

   Change from baseline in the number of steps

6. Change in activity [18 months]

   Change from baseline in the number of steps

7. Change in cognitive function [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 [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 [12 months]

   Change from baseline in maximal oxygen consumption measured with peak oxygen volume

10. Change in fitness [18 months]

    Change from baseline in maximal oxygen consumption measured with peak oxygen volume

11. Change in quality of life [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 [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 [12 months]

    Time to initiation of dopaminergic therapy

14. Change in blood derived marker of inflammation [12 months]

    Change from baseline in C-reactive protein

15. Change in blood derived marker of inflammation [18 months]

    Change from baseline in C-reactive protein

16. Change in blood derived marker of neuronal development [12 months]

    Change from baseline in brain derived neurotrophic factor (BDNF)

17. Change in blood derived marker of neuronal development [18 months]

    Change from baseline in brain derived neurotrophic factor (BDNF)

Other Outcome Measures

1. Change in stride length [12 months]

   Change in stride length assessed using OPAL movement monitors during the 6 minute walk test

2. Change in stride length [18 months]

   Change in stride length assessed using OPAL movement monitors during the 6 minute walk test

3. Change in turning velocity [12 months]

   Change in turning velocity assessed using OPAL movement monitors during the 6 minute walk test

4. Change in turning velocity [18 months]

   Change in turning velocity assessed using OPAL movement monitors during the 6 minute walk test

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 80 Years
• Sexes Eligible for Study: 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:

• 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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	University of California, San Francisco	San Francisco	California	United States	94143
3	University of Colorado, Denver	Aurora	Colorado	United States	80204
4	University of Florida	Gainesville	Florida	United States	32611
5	Morehouse School of Medicine	Atlanta	Georgia	United States	30310
6	Emory University	Atlanta	Georgia	United States	30322
7	Northwestern University	Chicago	Illinois	United States	60611
8	Rush University Medical Center	Chicago	Illinois	United States	60612
9	Iowa State University	Ames	Iowa	United States	50011
10	Louisiana State University	Baton Rouge	Louisiana	United States	70803
11	Boston University (Charles River Campus)	Boston	Massachusetts	United States	02215
12	University of Michigan	Ann Arbor	Michigan	United States	48109
13	University of Minnesota	Minneapolis	Minnesota	United States	55455
14	Washington University St. Louis	Saint Louis	Missouri	United States	63130
15	New York University Langone Health	New York	New York	United States	10016
16	Columbia University Medical Center	New York	New York	United States	10032
17	University of Cincinnati	Cincinnati	Ohio	United States	45221
18	Cleveland Clinic	Cleveland	Ohio	United States	44195
19	Ohio Health	Columbus	Ohio	United States	43214
20	Kent State University	Kent	Ohio	United States	44240
21	Oregon Health & Science University	Portland	Oregon	United States	97239
22	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
23	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15219
24	University of Texas Medical Brand	Galveston	Texas	United States	77555
25	University of Utah	Salt Lake City	Utah	United States	84112
26	University of Virginia	Charlottesville	Virginia	United States	22904
27	University of Alberta	Edmonton		Canada

Sponsors and Collaborators

• Northwestern University
• University of Pittsburgh
• The Parkinson Study Group

Investigators

• Principal Investigator: Daniel M Corcos, PhD, Northwestern University

Study Documents (Full-Text)

• Informed Consent Form - Jul 12, 2022

More Information

Publications

• 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.
• 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.

• Responsible Party: Daniel Corcos, Professor of Physical Therapy and Human Movement Sciences, Northwestern University
• ClinicalTrials.gov Identifier: NCT04284436
• Other Study ID Numbers: 1U01NS113851-01
• First Posted: Feb 25, 2020
• Last Update Posted: Aug 5, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Parkinson Disease

Study Results

No Results Posted as of Aug 5, 2022