Study in Parkinson Disease of Exercise

Parkinson Disease Clinical Trial

— SPARX3  

Official title:

Study in Parkinson Disease of Exercise Phase 3 Clinical Trial: SPARX3

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04284436
• Other study ID #: 1U01NS113851-01
• Status: Recruiting
• Phase: N/A
• Start date: August 30, 2021
• Est. completion date: July 31, 2028

Study information

• Verified date: May 2024
• Source: Northwestern University
• Contact: Elizabeth Joslin
• Phone: 309-922-7254
• Email: elizabeth.joslin[@]northwestern.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 370
• Est. completion date: July 31, 2028
• Est. primary completion date: July 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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).

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Behavioral:
• Treadmill walking
Treadmill walking 4 days per week for 30 minutes in the target heart rate

Locations

Country	Name	City	State
Canada	University of Alberta	Edmonton
United States	Iowa State University	Ames	Iowa
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Morehouse School of Medicine	Atlanta	Georgia
United States	University of Colorado, Denver	Aurora	Colorado
United States	Louisiana State University	Baton Rouge	Louisiana
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Boston University (Charles River Campus)	Boston	Massachusetts
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Ohio Health	Columbus	Ohio
United States	University of Florida	Gainesville	Florida
United States	Kent State University	Kent	Ohio
United States	University of Minnesota	Minneapolis	Minnesota
United States	Columbia University Medical Center	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Washington University St. Louis	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	UT Health San Antonio	San Antonio	Texas
United States	University of California, San Francisco	San Francisco	California

Sponsors (3)

Lead Sponsor	Collaborator
Northwestern University	The Parkinson Study Group, University of Pittsburgh

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in stride length	Change in stride length assessed using OPAL movement monitors during the 6 minute walk test	12 months
Other	Change in stride length	Change in stride length assessed using OPAL movement monitors during the 6 minute walk test	18 months
Other	Change in turning velocity	Change in turning velocity assessed using OPAL movement monitors during the 6 minute walk test	12 months
Other	Change in turning velocity	Change in turning velocity assessed using OPAL movement monitors during the 6 minute walk test	18 months
Primary	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.	12 months
Secondary	Change in dopaminergic activity	Change from baseline in the striatal specific binding ratio (SSBR) as measured by dopamine transporter imaging	12 months
Secondary	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.	18 months
Secondary	Change in walking capacity	Change from baseline in distance in 6-minute walk	12 months
Secondary	Change in walking capacity	Change from baseline in distance in 6-minute walk	18 months
Secondary	Change in activity	Change from baseline in the number of steps	12 months
Secondary	Change in activity	Change from baseline in the number of steps	18 months
Secondary	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.	12 months
Secondary	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.	18 months
Secondary	Change in fitness	Change from baseline in maximal oxygen consumption measured with peak oxygen volume	12 months
Secondary	Change in fitness	Change from baseline in maximal oxygen consumption measured with peak oxygen volume	18 months
Secondary	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.	12 months
Secondary	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.	18 months
Secondary	Initiation of dopaminergic therapy	Time to initiation of dopaminergic therapy	12 months
Secondary	Change in blood derived marker of inflammation	Change from baseline in C-reactive protein	12 months
Secondary	Change in blood derived marker of inflammation	Change from baseline in C-reactive protein	18 months
Secondary	Change in blood derived marker of neuronal development	Change from baseline in brain derived neurotrophic factor (BDNF)	12 months
Secondary	Change in blood derived marker of neuronal development	Change from baseline in brain derived neurotrophic factor (BDNF)	18 months