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Completed

NCT Number: NCT03213873

Neuroplasticity in Parkinson´s Disease After Training

This project aims to determine the effects of the HiBalance program on neuroplastic changes in people with mild to moderate Parkinson´s disease. The main hypothesis is that highly challenging exercise will lead to greater gait and balance ability, increased levels of physical activity and an improved health related quality of life. The investigators further hypothesize that neuroplasticity changes will be seen in corresponding areas of the brain, neuropsychological changes on cognitive test measures, and that exercise will inhibit the degeneration of dopaminergic neurons in the brain through the mediation of neurotrophic factors.

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Key information

About this study

Parkinson's disease (PD) is a neurodegenerative disease affecting many physiological systems essential for balance control. New findings suggest that intensive, challenging and cognitively demanding exercises could induce neuroplasticity in PD. A new balance training (the HiBalance program) have therefore been developed; emphasizing critical aspects of balance control through highly challenging and progressive exercises incorporating dual/multi-tasking (Conradsson et al, 2012). In an RCT, the HiBalance-program was shown to improve balance, gait and physical activity level in favor for the training group (Conradsson et al, 2015). In this proposal the investigators will combine physiotherapy, neurology and neuroimaging to characterise and determine the effects on physical and cognitive symptoms as well as structural and functional changes and wet biomarkers in the brain after the training.

Participants will be recruited through Karolinska University Hospital and via announcements in relevant forums like for instance the Swedish Parkinson Association. According to earlier power calculations for detecting effects in balance and gait measures after this particular intervention, the investigators anticipate 40 to 50 participants in each group to detect significant changes.

The investigators will perform both per protocol analysis and intention to treat analysis using mixed model or repeated measurement ANOVAs if the data is normally distributed.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Diagnosis of idiopathic Parkinson´s disease
  • Hoehn & Yahr 2-3
  • ≥ 60 years of age
  • Be able to ambulate indoors without mobility aid
  • Balance impairment

Exclusion criteria

  • =< 21 points on MoCA
  • Other medical conditions that could substantially influence balance performance, voice or speech performance or participation in the interventions
  • Participating in an intensive exercise program for balance or speech during the last six months.

Additional exclusion criteria for the brain imaging will include the presence of; pacemakers, deep brain stimulators or other MRI incompatible implants, claustrophobia, inability to hear instructions without hearing aid, unilateral or bilateral blindness, severe diplopia, tremor, dyskinesia or dystonia.

Treatment and study plan

HiBalance

Behavioral

Intervention of highly challenging balance training for 10 weeks.

Speech and communication therapy

Behavioral

Intervention conducted by speech and language therapist for 10 weeks.

Primary outcomes

  1. Mini-BESTest

    Time frame: Pre intervention baseline and post intervention at 10 weeks

    Mini-Balance Evaluation Systems Test a rating scale for dynamic balance incorporating 14 different balance and gait items that were assessed by a physical therapist on a scale from 0-2. Maximum points 28.

    0-28 points with higher scores indicating better balance control

Secondary outcomes

  1. Gait Parameters

    Time frame: Pre intervention baseline and post intervention at 10 weeks

    Gait speed in m/sec

  2. Neuropsychological Tests

    Time frame: Pre intervention baseline and post intervention at 10 weeks

    Composite measure of executive functions of four tests:

    • letter fluency
    • the verbal fluency test: category switching
    • the colour-word interference test: switch condition (Test 1, 2 and 3 from the Delis-Kaplan Executive Function System)
    • the digit span total score (from Wechsler Adult Intelligence Scale)

    First, the scores of each of the four tests were standardised into z-scores using pre-scores. Models using different test were compared. The model including all four tests and using the robust diagonally weighted least square estimation was chosen based on fit values. Factor loadings of the model: verbal fluency = 1.000, the verbal fluency test: category switching= 0.887, the colour-word interference test: switch condition= -0.855, the digit span total score= 0.813. Last, the z-scores of each test and person were multiplied with the factor loadings and added together to create a sum score for each person and time point. A higher value = greater executive functions

  3. Quality of Life Questionnaires

    Time frame: Pre intervention baseline and post intervention at 10 weeks

    The Parkinson's Disease Questionnaire (PDQ-39) assesses how often people with Parkinson's experience difficulties across 8 dimensions of daily living (mobility, activities of daily living, emotional well-being, stigma, social support, cognitions, communications and bodily discomfort).

    The sum score is as a percentage score ranging between 0 and 100. Higher is better

  4. Movement Disorder Society - Unified Parkinsons Disease Rating Scale (MDS-UPDRS)

    Time frame: Pre intervention baseline and post intervention at 10 weeks

    Disease severity/symtoms in Parkinson's disease, Movement Disorder Society - Unified Parkinsons disease rating scale (MDS-UPDRS) Total score.

    Higher score is worse, ranging from 0-272

  5. Physical Activity Measured With Accelerometers

    Time frame: Pre intervention baseline and post intervention at 10 weeks

    Number of Steps per day.

  6. Structural Magnetic Resonance Imaging

    Time frame: Pre intervention baseline and post intervention at 10 weeks

    Intervention dependent changes in brain structure i.e. gray matter volume measured as voxels Analyses defined as: were there any significant clusters of voxels explained by the interaction of group and time. In other words, were there significant changes in voxel activity that depended on the interventions when using a cluster-based threshold using group statistics..

    Note that it is not possible to report this outcome per group. Additionally, MR statistics are not reported as measures of central tendency such as the mean or any alternatives provided.

  7. Task-induced Brain Activity as Measured by Functional Magnetic Resonance Imaging

    Time frame: Pre intervention baseline and post intervention at 10 weeks

    Intervention dependent changes in task-induced brain activity, voxel-wise analyses of whole brain. (Name of the task performed during fMRI; the serial reaction time task.)

    Analyses defined as: were there any significant clusters of voxels explained by the interaction of group and time. In other words, were there significant changes in voxel activity that depended on the interventions when using a cluster-based threshold. The measure type number was chosen because we estimated the number of significant clusters of voxels. Group statistics were perfromed

    Note that for task fMRI interaction analyses, there are no meaningful values to report for the groups respectively.

  8. Wet Biomarkers

    Time frame: Pre intervention baseline and post intervention at 10 weeks

    Mature Brain-derived neurotrophic factor (mBDNF) in serum

Other outcomes

  1. Dysarthria

    Time frame: Pre intervention baseline

    The Dysarthria Assessment also includes the Questionnaire on Acquired Speech Disorders (QASD, Swedish: Självsvarsformulär om Förvärvade Talstörningar) which is a self-report instrument that captures the subjective symptoms and experiences of individuals living with acquired speech disorders. Three subscales are included: "My Speech and Language", "Speech and Language in Social Interaction", and "Personal and Environmental Factors". Each item is rated on a four-point scale from 0 (definitely false) to 3 (definitely true), with higher scores indicating more severe symptoms. The overall QASD score was determined by calculating the average score of all sub-scales.

  2. Voice Strength

    Time frame: Pre intervention baseline and post intervention at 10 weeks

    The recordings were performed according to standardised routines for high-quality recordings in a sound-proof recording studio with the equipment Sony Digital Audio Tape Deck DTC-ZE700 and the software Sopran (version 1.0.22 © Tolvan Data). Measures were performed by a speech and language pathologist.

    The outcome measure from the studio recordings used in the present study was mean voice sound level (dB SPL) in reading a Swedish standardised text.

Sponsors and collaborators

Lead sponsor

Karolinska Institutet

Other

Collaborators

  • Karolinska University Hospital

Registry information

Official study title

Effects of the HiBalance-program: Linking Clinical Signs and Symptoms to Changes in the Brain in People With Parkinson´s Disease

Acronym: BETA-PD

Important dates

Study start
2017
Primary completion
2019
Study completion
2019
First posted
Jul 11, 2017
Registry last updated
Mar 7, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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