The EXPANd trial: effects of exercise and exploring neuroplastic changes in people with Parkinson's disease: a study protocol for a double-blinded randomized controlled trial

Abstract

Background: Parkinson's disease (PD) affects many physiological systems essential for balance control. Recent studies suggest that intensive and cognitively demanding physical exercise programs are capable of inducing plastic brain changes in PD. We have developed a highly challenging balance training (the HiBalance) program that emphasizes critical aspects of balance control through progressively introducing more challenging exercises which incorporates dual-tasking. Earlier studies have shown it to be effective in improving balance, gait and dual-tasking. The study design has thereafter been adjusted to link intervention-induced behavioral changes to brain morphology and function. Specifically, in this randomized controlled trial, we will determine the effects of the HiBalance program on balance, gait and cognition and relate this to task-evoked functional MRI (fMRI), as well as brain-derived neurotrophic factor (BDNF) in participants with mild-moderate PD.

Methods: One hundred participants with idiopathic PD, Hoehn & Yahr stage 2 or 3, ≥ 60 years of age, ≥ 21 on Montreal Cognitive Assessment will be recruited in successive waves and randomized into either the HiBalance program or to an active control group (the HiCommunication program, targeting speech and communication). Both interventions will be performed in small groups, twice a week with 1 h sessions for 10 weeks. In addition, a 1 h, once a week, home exercise program will also be performed. A double-blinded design will be used. At the pre- and post-assessments, participants will be assessed on balance (main outcome), gait, cognitive functions, physical activity, voice/speech function, BDNF in serum and fMRI (3 T Philips) during performance of motor-cognitive tasks.

Discussion: Since there is currently no cure for PD, findings of neuroplastic brain changes in response to exercise would revolutionize the way we treat PD, and, in turn, provide new hope to patients for a life with better health, greater independence and improved quality of life.

Trial registration: ClincalTrials.gov: NCT03213873, first posted July 11, 2017.

Keywords: Balance; Cognition; Dual-task; Exercise; Gait; Imaging; Magnetic resonance neural growth factor; Neuroplasticity; Parkinson’s disease.

Fig. 1

Flowchart of the study

Fig. 2

illustrates the experimental set-up of the single tast (ST) and dual-task (DT) during the functional magnetic resonance imaging (fMRI). During both visu-motor tasks four white circles are shown on a black screen with one circle blinking (turning grey) every 1.2 s. The participants will have a 2-button response box in each hand and use their index and middle fingers to respond to the circle turning grey by pressing the corresponding button. During the DT, participants will also perform a counting task, i.e. count how many white plus sign appearing on the screen during the block. After each DT-block, participants will be given four alternatives and respond with the corresponding button how many plus-signs they have counted