Neuroplasticity in Parkinson´s Disease After Training

Not Applicable

Completed

Conditions: Parkinson Disease
Physical Activity
Gait Disorders, Neurologic
Neural Degeneration

Interventions: Behavioral: HiBalance
Behavioral: Speech and communication therapy

Registration Number: NCT03213873

Lead Sponsor: Karolinska Institutet

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 95

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HiBalance	HiBalance	The HiBalance program is based on scientifically well-established principles of exercise training and postural control as well as current research on training in PD. The training will be conducted as a progressive individually adjusted group program in order to challenge the specific balance disorder of every participant and endorse progression. The intervention will be performed for an hour, 2 times/week in groups of six to eight participants for a total of 10 weeks and one home training session on their own.
Speech therapy	Speech and communication therapy	The control group will receive a group treatment (2 times/w for 10 w + 1 home training session) consisting of speech and communication therapy performed by a speech therapist. This intervention will be performed in a sitting position. The speech and communication treatment will aim at increasing vocal loudness and improving articulatory precision. Level of difficulty is gradually increased by progressing from using loud voice and clear speech in short and automatized utterances, to using the same technique in more complex sentences and situations. The group format is used to practice techniques in communicative situations and also to introduce increasing level of multitasking by combining speech training with cognitively more challenging tasks in the group training.

Primary Outcome Measures

Name	Time	Method
Mini-BESTest	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 Outcome Measures

Name	Time	Method
Gait Parameters	Pre intervention baseline and post intervention at 10 weeks	Gait speed in m/sec
Neuropsychological Tests	Pre intervention baseline and post intervention at 10 weeks	Composite measure of executive functions of four tests: 1. letter fluency 2. the verbal fluency test: category switching 3. the colour-word interference test: switch condition (Test 1, 2 and 3 from the Delis-Kaplan Executive Function System) 4. 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
Quality of Life Questionnaires	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
Movement Disorder Society - Unified Parkinsons Disease Rating Scale (MDS-UPDRS)	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
Physical Activity Measured With Accelerometers	Pre intervention baseline and post intervention at 10 weeks	Number of Steps per day.
Structural Magnetic Resonance Imaging	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.
Task-induced Brain Activity as Measured by Functional Magnetic Resonance Imaging	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.
Wet Biomarkers	Pre intervention baseline and post intervention at 10 weeks	Mature Brain-derived neurotrophic factor (mBDNF) in serum