Parkinson's DiseaseCYCLENCT01636297
The Cyclical Lower-extremity Exercise for Parkinson's Trial
A study testing Forced exercise and Voluntary exercise in people with Parkinson's Disease, run by The Cleveland Clinic at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 75 years
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- Forced exercise and Voluntary exercise
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2013to Dec 2017
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Parkinson's Disease
- Being tested
- Forced exercise, Voluntary exercise
- Keywords
- Parkinson's disease, Exercise
- Medical subject headings
- Parkinson Disease, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Forced exerciseBehavioural
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
Voluntary exerciseBehavioural
Exercise on a stationary cycle without motor assistance. Intervention was administered 3 times per week for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| Forced exercise | Experimental | Exercise on stationary cycle that was controlled by a motor to augment voluntary cycling rate by 35% Receives: Behavioral: Forced exercise |
| Voluntary Exercise | Experimental | Exercise on a stationary cycle without motor assistance Receives: Behavioral: Voluntary exercise |
| No Exercise | No intervention | Participants received no exercise intervention and served as the control group |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Change from baseline over 16 weeks
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.
Measured: Change from baseline over 16 weeks
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.
Measured: Change from baseline to end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2012 (estimated)
- Study startJun 2013
- Primary completionDec 2016
- Study completionDec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jay Alberts, The Cleveland Clinic
- Investigators
- Jay Alberts, PhD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01636297
- Sponsor's protocol ID
- 1R01NS073717-01
- Acronym
- CYCLE
- Status last verified
- Aug 2018
- First submitted
- 6 Jul 2012
- Last updated
- 26 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Ernst M, Folkerts AK, Gollan R, Lieker E, Caro-Valenzuela J, Adams A, Cryns N, Monsef I, Dresen A, Roheger M, Eggers C, Skoetz N, Kalbe E. Physical exercise for people with Parkinson's disease: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2024 Apr 8;4(4):CD013856. doi: 10.1002/14651858.CD013856.pub3.
PubMed 38588457Ernst M, Folkerts AK, Gollan R, Lieker E, Caro-Valenzuela J, Adams A, Cryns N, Monsef I, Dresen A, Roheger M, Eggers C, Skoetz N, Kalbe E. Physical exercise for people with Parkinson's disease: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2023 Jan 5;1(1):CD013856. doi: 10.1002/14651858.CD013856.pub2.
PubMed 36602886Jansen 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.
PubMed 33932704Penko 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.
PubMed 33453190Rosenfeldt 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.
PubMed 33394100Rosenfeldt 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.
PubMed 25902768
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Cyclical Lower-extremity Exercise for Parkinson's Trial
- ClinicalTrials.gov ID
- NCT01636297
- Acronym / sponsor ID
- CYCLE / 1R01NS073717-01
- Conditions
- Parkinson's Disease
- Keywords
- Parkinson's disease, Exercise
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Study start
- Jun 2013
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 10 Jul 2012 (estimated)
- Results
- Posted 26 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Forced exercise | Experimental | Behavioral: Forced exerciseExercise on stationary cycle that was controlled by a motor to augment voluntary cycling rate by 35% |
| Voluntary Exercise | Experimental | Behavioral: Voluntary exerciseExercise on a stationary cycle without motor assistance |
| No Exercise | No intervention | –Participants received no exercise intervention and served as the control group |
Who may qualify
- Ages
- 30 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Forced exerciseExercise 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 | Behavioural | Forced exercise |
| Voluntary exerciseExercise on a stationary cycle without motor assistance. Intervention was administered 3 times per week for 8 weeks | Behavioural | Voluntary Exercise |
Primary outcome
MDS-UPDRS Motor III Score
Time frame: Change from baseline over 16 weeks
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
Time frame: Change from baseline over 16 weeks
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
Time frame: Change from baseline to end of treatment
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38588457Ernst M, Folkerts AK, Gollan R, Lieker E, Caro-Valenzuela J, Adams A, Cryns N, Monsef I, Dresen A, Roheger M, Eggers C, Skoetz N, Kalbe E. Physical exercise for people with Parkinson's disease: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2024 Apr 8;4(4):CD013856. doi: 10.1002/14651858.CD013856.pub3.
- Derived from this study: PubMed 36602886Ernst M, Folkerts AK, Gollan R, Lieker E, Caro-Valenzuela J, Adams A, Cryns N, Monsef I, Dresen A, Roheger M, Eggers C, Skoetz N, Kalbe E. Physical exercise for people with Parkinson's disease: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2023 Jan 5;1(1):CD013856. doi: 10.1002/14651858.CD013856.pub2.
- Derived from this study: PubMed 33932704Jansen 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.
- Derived from this study: PubMed 33453190Penko 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.
- Derived from this study: PubMed 33394100Rosenfeldt 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.
- Derived from this study: PubMed 25902768Rosenfeldt 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.
Related trials for Parkinson's Disease
Recruiting
Investigating Basal Ganglia-Cortical Physiology During Sleep and Its Modulation by Adaptive Deep Brain Stimulation in Parkinson Disease
Parkinson's Disease (PD)
Active, not recruitingPhase 2
A Study to Evaluate Efficacy, Safety and Tolerability of Hydroxychloroquine in Subjects With Parkinson's Disease
Parkinson&Amp;#39;s Disease
Not yet recruiting
Cognitive-Motor Training for Gait Adaptability in Parkinson Disease
Parkinson Disease
RecruitingPhase 2
A Phase 2 Study and Open-Label Extension of NEU-411 in Companion Diagnostic-Positive Participants With Early Parkinson's Disease
Parkinson Disease, Parkinson
RecruitingPhase 2/3
A Study of Buntanetap in Participants With PD
Parkinson's Disease (PD), Deep Brain Stimulation
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jay Alberts, PhD principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Forced exercise and Voluntary exercise in people with Parkinson's Disease, run by The Cleveland Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MDS-UPDRS Motor III Score (time frame: Change from baseline over 16 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01636297, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2018.