Gait Disorders, Neurologic, Neural Degeneration, Parkinson Disease, Physical Activity
Conditions
Keywords
Balance control, Exercise, Magnetic Resonance Imaging, Functional Magnetic Resonance Imaging
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.
Interventions
BEHAVIORALHiBalance
Intervention of highly challenging balance training for 10 weeks.
BEHAVIORALSpeech and communication therapy
Intervention conducted by speech and language therapist for 10 weeks.
Sponsors
Karolinska University Hospital
Karolinska Institutet
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Investigator and outcome assessors are masked to group allocation at baseline assessment. Care providers are masked to results of the assessments. Participants are masked to the studied intervention/treatment.
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Dysarthria | 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. |
| Voice Strength | 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. |
Countries
Sweden
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
HiBalance: Intervention of highly challenging balance training for 10 weeks. | 48 |
| Speech 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.
Speech and communication therapy: Intervention conducted by speech and language therapist for 10 weeks. | 47 |
| Total | 95 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Diagnosed w atypical PD after randomization | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Withdrawal by Subject | 8 | 9 |
Baseline characteristics
| Characteristic | Speech Therapy | Total | HiBalance |
|---|---|---|---|
| Age, Continuous | 71.1 years STANDARD_DEVIATION 6.3 | 71.1 years STANDARD_DEVIATION 6.1 | 71 years STANDARD_DEVIATION 5.9 |
| Disease stage Hoehn & Yahr Hoehn Yahr Stage 2 | 34 Participants | 73 Participants | 39 Participants |
| Disease stage Hoehn & Yahr Hoehn Yahr Stage 3 | 13 Participants | 22 Participants | 9 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Sweden | 47 participants | 95 participants | 48 participants |
| Sex: Female, Male Female | 17 Participants | 35 Participants | 18 Participants |
| Sex: Female, Male Male | 30 Participants | 60 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 48 | 0 / 47 |
| other Total, other adverse events | 8 / 48 | 0 / 47 |
| serious Total, serious adverse events | 0 / 48 | 0 / 47 |
Outcome results
Primary
Mini-BESTest
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
Time frame: Pre intervention baseline and post intervention at 10 weeks
Population: All participants randomised included using intention-to-treat-analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HiBalance | Mini-BESTest | Pre, observed values | 20.7 score on a scale | Standard Deviation 3.4 |
| HiBalance | Mini-BESTest | Post, observed values | 22.1 score on a scale | Standard Deviation 3 |
| Speech Therapy | Mini-BESTest | Pre, observed values | 21.0 score on a scale | Standard Deviation 3.5 |
| Speech Therapy | Mini-BESTest | Post, observed values | 21.8 score on a scale | Standard Deviation 3.1 |
p-value: 0.5795% CI: [-1, 1.9]Mixed Models Analysis
Secondary
Gait Parameters
Gait speed in m/sec
Time frame: Pre intervention baseline and post intervention at 10 weeks
Population: All participants randomised were included using intention-to-treat analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HiBalance | Gait Parameters | Post, observed values | 1.3 m/sec | Standard Deviation 0.2 |
| HiBalance | Gait Parameters | Pre, observed values | 1.2 m/sec | Standard Deviation 0.2 |
| Speech Therapy | Gait Parameters | Pre, observed values | 1.2 m/sec | Standard Deviation 0.2 |
| Speech Therapy | Gait Parameters | Post, observed values | 1.2 m/sec | Standard Deviation 0.2 |
p-value: 0.2595% CI: [-0.03, 0.12]Mixed Models Analysis
Secondary
Movement Disorder Society - Unified Parkinsons Disease Rating Scale (MDS-UPDRS)
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
Time frame: Pre intervention baseline and post intervention at 10 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HiBalance | Movement Disorder Society - Unified Parkinsons Disease Rating Scale (MDS-UPDRS) | Pre, observed values | 51.0 score on a scale | Standard Deviation 18.8 |
| HiBalance | Movement Disorder Society - Unified Parkinsons Disease Rating Scale (MDS-UPDRS) | Post, observed values | 48.2 score on a scale | Standard Deviation 17.8 |
| Speech Therapy | Movement Disorder Society - Unified Parkinsons Disease Rating Scale (MDS-UPDRS) | Pre, observed values | 50.4 score on a scale | Standard Deviation 15.5 |
| Speech Therapy | Movement Disorder Society - Unified Parkinsons Disease Rating Scale (MDS-UPDRS) | Post, observed values | 45.8 score on a scale | Standard Deviation 16.8 |
Secondary
Neuropsychological Tests
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
Time frame: Pre intervention baseline and post intervention at 10 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HiBalance | Neuropsychological Tests | Pre, observed values | 0.6 z-scores | Standard Deviation 2.6 |
| HiBalance | Neuropsychological Tests | Post, observed values | 1.5 z-scores | Standard Deviation 2.6 |
| Speech Therapy | Neuropsychological Tests | Pre, observed values | -0.7 z-scores | Standard Deviation 2.4 |
| Speech Therapy | Neuropsychological Tests | Post, observed values | 0.1 z-scores | Standard Deviation 3 |
p-value: 0.7595% CI: [-0.8, 1.1]Mixed Models Analysis
Secondary
Physical Activity Measured With Accelerometers
Number of Steps per day.
Time frame: Pre intervention baseline and post intervention at 10 weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| HiBalance | Physical Activity Measured With Accelerometers | Pre, observed values | 4936.6 steps per day |
| HiBalance | Physical Activity Measured With Accelerometers | Post, observed values | 4800.8 steps per day |
| Speech Therapy | Physical Activity Measured With Accelerometers | Pre, observed values | 5462.4 steps per day |
| Speech Therapy | Physical Activity Measured With Accelerometers | Post, observed values | 5609.5 steps per day |
Secondary
Quality of Life Questionnaires
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
Time frame: Pre intervention baseline and post intervention at 10 weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| HiBalance | Quality of Life Questionnaires | Pre, observed values | 19.7 score on a scale |
| HiBalance | Quality of Life Questionnaires | Post, observed values | 17.5 score on a scale |
| Speech Therapy | Quality of Life Questionnaires | Pre, observed values | 17.8 score on a scale |
| Speech Therapy | Quality of Life Questionnaires | Post, observed values | 11.9 score on a scale |
Secondary
Structural Magnetic Resonance Imaging
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.
Time frame: Pre intervention baseline and post intervention at 10 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HiBalance | Structural Magnetic Resonance Imaging | 0 Significant clusters of voxels |
| Speech Therapy | Structural Magnetic Resonance Imaging | 0 Significant clusters of voxels |
Secondary
Task-induced Brain Activity as Measured by Functional Magnetic Resonance Imaging
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.
Time frame: Pre intervention baseline and post intervention at 10 weeks
Population: All participants without missing or too low-quality fMRI data were included
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HiBalance | Task-induced Brain Activity as Measured by Functional Magnetic Resonance Imaging | 0 significant clusters of voxels |
| Speech Therapy | Task-induced Brain Activity as Measured by Functional Magnetic Resonance Imaging | 0 significant clusters of voxels |
Secondary
Wet Biomarkers
Mature Brain-derived neurotrophic factor (mBDNF) in serum
Time frame: Pre intervention baseline and post intervention at 10 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HiBalance | Wet Biomarkers | Pre, observed values | 38010.8 pg/mL | Standard Deviation 7956.7 |
| HiBalance | Wet Biomarkers | Post, observed values | 37169.4 pg/mL | Standard Deviation 8044.6 |
| Speech Therapy | Wet Biomarkers | Pre, observed values | 37805.3 pg/mL | Standard Deviation 5928.3 |
| Speech Therapy | Wet Biomarkers | Post, observed values | 35945.8 pg/mL | Standard Deviation 6208.5 |
Other Pre-specified
Dysarthria
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.
Time frame: Pre intervention baseline
Population: This variable were never analysed pre and post since it is not sensitive in patients with mild dysarthria. The variable was just used for describing the group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HiBalance | Dysarthria | 0.66 score on a scale | Standard Deviation 0.44 |
| Speech Therapy | Dysarthria | 0.43 score on a scale | Standard Deviation 0.35 |
Other Pre-specified
Voice Strength
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.
Time frame: Pre intervention baseline and post intervention at 10 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HiBalance | Voice Strength | Pre, observed values | 70.3 dB | Standard Deviation 3.5 |
| HiBalance | Voice Strength | Post, observed values | 70.6 dB | Standard Deviation 3.9 |
| Speech Therapy | Voice Strength | Pre, observed values | 70.8 dB | Standard Deviation 4 |
| Speech Therapy | Voice Strength | Post, observed values | 73.0 dB | Standard Deviation 4 |