The Cyclical Lower-extremity Exercise for Parkinson's Trial
Condition: Parkinson's Disease
MeSH terms: Parkinson Disease
Study type: Interventional

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.
    

Intervention name(s): Forced exercise; Voluntary exercise
Intervention type(s): Behavioral; Behavioral
Intervention description(s): 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; Exercise on a stationary cycle without motor assistance. Intervention was administered 3 times per week for 8 weeks
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Parkinson's disease; Exercise