The Cyclical Lower-extremity Exercise for Parkinson's Trial (CYCLE)
Primary Purpose
Parkinson's Disease
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Forced exercise
Voluntary exercise
Sponsored by
About this trial
This is an interventional treatment trial for Parkinson's Disease focused on measuring Parkinson's disease, Exercise
Eligibility Criteria
Inclusion Criteria:
- Able to provide informed consent.
- Clinical diagnosis of idiopathic PD. The diagnosis of PD will be based on the presence of at least two of the cardinal signs of this disorder (akine¬sia/bradykinesia, rest tremor, rigidity, gait and postural instability) with at least one of the signs being rest tremor or akinesia/bradykinesia.
- Hoehn and Yahr stage II-III when off PD medication.
- UPDRS motor score between 6-45 out of a maximum of 108 when off PD medication.
- Stable anti-parkinsonian medication for one month prior to study enrollment or consistent in desire to stay off anti-parkinson medication.
- Age between 30 and 75 years.
Exclusion Criteria:
- Clinically significant medical disease that would increase the risk of exercise-related complications (e.g. cardiac or pulmonary disease, diabetes mellitus, hypertension, stroke).
- Dementia as evidenced by a score less than 116 on the Mattis Dementia Rating Scale.
- Other medical or musculoskeletal contraindications to exercise.
- Undergone any surgical procedure for treatment of PD, DBS, pallidotomy or thalamotomy
Sites / Locations
- Cleveland Clinic
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
No Intervention
Arm Label
Forced exercise
Voluntary Exercise
No Exercise
Arm Description
Exercise on stationary cycle that was controlled by a motor to augment voluntary cycling rate by 35%
Exercise on a stationary cycle without motor assistance
Participants received no exercise intervention and served as the control group
Outcomes
Primary Outcome Measures
MDS-UPDRS Motor III Score
The Movement Disorder Society-Unified Parkinson's disease Rating Scale (MDS-UPDRS) Motor III Score is a subscale of the MDS-UPDRS. The MDS-UPDRS III is the sum of 33 scores that evaluate Parkinson's disease motor symptoms on a scale from 0 to 4 points. A score of 0 indicated no symptom is present and a maximum score of 4 indicates the most severe symptom, the total scale range is 0-132, where higher scores indicate more severe symptoms. The primary outcome is the change in total motor subscale score in the MDS-UPDRS from baseline versus the three end of treatment (EOT) assessments.
Trail Making Test
The Trail Making test is a test of executive function and the primary outcome is total test time. The total time that it takes to complete the test was recorded at baseline and then after the end of treatment. Test time recording begins with the start of the test and ends when the test is completed. Longer times indicate worse executive function. The outcome is the change in test time on the trail making test from baseline to the end of treatment (EOT) assessment.
Number of Participants With Increased Motor Cortex and Thalamus Connectivity
The primary outcome measure will number of patients that increased their connection between the motor cortex and the thalamus. The functional connection was assessed using functional magnetic resonance imaging. The outcome measure was change in connectivity from baseline to end of treatment.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01636297
Brief Title
The Cyclical Lower-extremity Exercise for Parkinson's Trial
Acronym
CYCLE
Official Title
The Cyclical Lower-extremity Exercise for Parkinson's Trial
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
June 2013 (undefined)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
December 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Cleveland Clinic
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to gain a better understanding of how exercise training affects motor/hand function and brain function in those diagnosed with Parkinson's disease. The investigators want to study if exercise will improve hand function and improve the level of brain activity.
Detailed Description
Current medical and surgical approaches to Parkinson's disease (PD) are expensive and associated with a variety of side effects that may compromise the patient's quality of life. Development of a non-drug, non-surgical therapeutic approach to improve motor function would provide an attractive adjunct to current PD treatment approaches. Promising results from animal exercise studies have not been translated to patients with PD.
Animal studies suggest forced-exercise produces an endogenous increase in neurotrophic factors. An increase in these factors is believed to improve the capacity of dopamine neurons to deliver dopamine and selectively increase dopamine levels within the dorsolateral striatum. Models of PD provide a theoretical framework for forced-exercise and explain why voluntary exercise is not associated with global improvements in motor function for PD patients. Based on model predictions, decreased motor cortical activation limits PD patients' ability to perform voluntary exercise at the relatively high rate used in animal studies that demonstrate a therapeutic benefit. Therefore, PD patients may not be able to exercise (voluntarily) at sufficiently high rates to trigger the endogenous release of neurotrophic factors thought to underlie global improvements in motor functioning. A safe lower extremity forced-exercise paradigm that augments PD patients voluntary exercise rates has been developed for humans in an ongoing R21 project. Similar to our initial study, PD patients completing an 8-week forced-exercise intervention exhibited nearly a 25% percent improvement in clinical motor ratings, patients completing a voluntary exercise intervention showed no improvement in clinical ratings. Our recent fMRI data indicate that an acute bout of forced-exercise in PD patients produces a similar subcortical and cortical activation pattern as is seen following administration of levodopa. Global improvements in motor function and increased neural activity suggest forced-exercise may be altering brain function in PD patients. The goal of this project is to determine and compare the effects of forced versus voluntary exercise on PD motor and non-motor function and associated changes in the pattern of neural activity.
A single-center, parallel-group, rater-blind, study in a 2:2:1 randomization is proposed. A total of 100 mild to moderate idiopathic PD patients will be randomized to a voluntary, forced or no-exercise control group. Exercise groups will exercise at identical aerobic intensities, however those in the forced group will be provided mechanical assistance to perform exercise 35% faster than their voluntary exercise rate.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Disease
Keywords
Parkinson's disease, Exercise
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
100 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Forced exercise
Arm Type
Experimental
Arm Description
Exercise on stationary cycle that was controlled by a motor to augment voluntary cycling rate by 35%
Arm Title
Voluntary Exercise
Arm Type
Experimental
Arm Description
Exercise on a stationary cycle without motor assistance
Arm Title
No Exercise
Arm Type
No Intervention
Arm Description
Participants received no exercise intervention and served as the control group
Intervention Type
Behavioral
Intervention Name(s)
Forced exercise
Intervention Description
Exercise on a stationary cycle that was controlled by a motor, to augment voluntary cycling rate by 35%. Intervention was administered 3 times per week for 8 weeks
Intervention Type
Behavioral
Intervention Name(s)
Voluntary exercise
Intervention Description
Exercise on a stationary cycle without motor assistance. Intervention was administered 3 times per week for 8 weeks
Primary Outcome Measure Information:
Title
MDS-UPDRS Motor III Score
Description
The Movement Disorder Society-Unified Parkinson's disease Rating Scale (MDS-UPDRS) Motor III Score is a subscale of the MDS-UPDRS. The MDS-UPDRS III is the sum of 33 scores that evaluate Parkinson's disease motor symptoms on a scale from 0 to 4 points. A score of 0 indicated no symptom is present and a maximum score of 4 indicates the most severe symptom, the total scale range is 0-132, where higher scores indicate more severe symptoms. The primary outcome is the change in total motor subscale score in the MDS-UPDRS from baseline versus the three end of treatment (EOT) assessments.
Time Frame
Change from baseline over 16 weeks
Title
Trail Making Test
Description
The Trail Making test is a test of executive function and the primary outcome is total test time. The total time that it takes to complete the test was recorded at baseline and then after the end of treatment. Test time recording begins with the start of the test and ends when the test is completed. Longer times indicate worse executive function. The outcome is the change in test time on the trail making test from baseline to the end of treatment (EOT) assessment.
Time Frame
Change from baseline over 16 weeks
Title
Number of Participants With Increased Motor Cortex and Thalamus Connectivity
Description
The primary outcome measure will number of patients that increased their connection between the motor cortex and the thalamus. The functional connection was assessed using functional magnetic resonance imaging. The outcome measure was change in connectivity from baseline to end of treatment.
Time Frame
Change from baseline to end of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Able to provide informed consent.
Clinical diagnosis of idiopathic PD. The diagnosis of PD will be based on the presence of at least two of the cardinal signs of this disorder (akine¬sia/bradykinesia, rest tremor, rigidity, gait and postural instability) with at least one of the signs being rest tremor or akinesia/bradykinesia.
Hoehn and Yahr stage II-III when off PD medication.
UPDRS motor score between 6-45 out of a maximum of 108 when off PD medication.
Stable anti-parkinsonian medication for one month prior to study enrollment or consistent in desire to stay off anti-parkinson medication.
Age between 30 and 75 years.
Exclusion Criteria:
Clinically significant medical disease that would increase the risk of exercise-related complications (e.g. cardiac or pulmonary disease, diabetes mellitus, hypertension, stroke).
Dementia as evidenced by a score less than 116 on the Mattis Dementia Rating Scale.
Other medical or musculoskeletal contraindications to exercise.
Undergone any surgical procedure for treatment of PD, DBS, pallidotomy or thalamotomy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jay Alberts, PhD
Organizational Affiliation
The Cleveland Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
33932704
Citation
Jansen AE, Koop MM, Rosenfeldt AB, Alberts JL. High intensity aerobic exercise improves bimanual coordination of grasping forces in Parkinson's disease. Parkinsonism Relat Disord. 2021 Jun;87:13-19. doi: 10.1016/j.parkreldis.2021.04.005. Epub 2021 Apr 20.
Results Reference
derived
PubMed Identifier
33453190
Citation
Penko AL, Zimmerman NM, Crawford M, Linder SM, Alberts JL. Effect of Aerobic Exercise on Cardiopulmonary Responses and Predictors of Change in Individuals With Parkinson's Disease. Arch Phys Med Rehabil. 2021 May;102(5):925-931. doi: 10.1016/j.apmr.2020.12.011. Epub 2021 Jan 14.
Results Reference
derived
PubMed Identifier
33394100
Citation
Rosenfeldt AB, Koop MM, Fernandez HH, Alberts JL. High intensity aerobic exercise improves information processing and motor performance in individuals with Parkinson's disease. Exp Brain Res. 2021 Mar;239(3):777-786. doi: 10.1007/s00221-020-06009-0. Epub 2021 Jan 4.
Results Reference
derived
PubMed Identifier
25902768
Citation
Rosenfeldt AB, Rasanow M, Penko AL, Beall EB, Alberts JL. The cyclical lower extremity exercise for Parkinson's trial (CYCLE): methodology for a randomized controlled trial. BMC Neurol. 2015 Apr 24;15:63. doi: 10.1186/s12883-015-0313-5.
Results Reference
derived
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The Cyclical Lower-extremity Exercise for Parkinson's Trial
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