Clinical trial NCT01636297: The Cyclical Lower-extremity Exercise for Parkinson's Trial
Official title: The Cyclical Lower-extremity Exercise for Parkinson's Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Parkinson's Disease
Keywords: Parkinson's disease
Exercise
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
First posted: 2012-07-10
Enrollment: 100
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: MDS-UPDRS Motor III Score
timeFrame: Change from baseline over 16 weeks
measure: Trail Making Test
timeFrame: Change from baseline over 16 weeks
measure: Number of Participants With Increased Motor Cortex and Thalamus Connectivity
timeFrame: Change from baseline to end of treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Jay Alberts, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.