Neuroplasticity in Parkinson´s Disease After Training (BETA-PD)

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

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.

Study Overview

• Status: Completed
• Conditions: Physical Activity; Parkinson Disease; Gait Disorders, Neurologic; Neural Degeneration
• Intervention / Treatment: Behavioral: HiBalance; Behavioral: Speech and communication therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Huddinge, Sweden, 14183
    • Karolinska Institutet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 56 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Behavioral: HiBalance; Intervention of highly challenging balance training for 10 weeks.
Active Comparator: 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.	Behavioral: Speech and communication therapy; Intervention conducted by speech and language therapist for 10 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Pre intervention baseline and post intervention at 10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gait Parameters	Gait speed in m/sec	Pre intervention baseline and post intervention at 10 weeks
Neuropsychological Tests	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	Pre intervention baseline and post intervention at 10 weeks
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	Pre intervention baseline and post intervention at 10 weeks
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	Pre intervention baseline and post intervention at 10 weeks
Physical Activity Measured With Accelerometers	Number of Steps per day.	Pre intervention baseline and post intervention at 10 weeks
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.	Pre intervention baseline and post intervention at 10 weeks
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.	Pre intervention baseline and post intervention at 10 weeks
Wet Biomarkers	Mature Brain-derived neurotrophic factor (mBDNF) in serum	Pre intervention baseline and post intervention at 10 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Pre intervention baseline
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.	Pre intervention baseline and post intervention at 10 weeks

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Collaborators: Karolinska University Hospital
• Investigators: Study Chair: Maria Eriksdotter, Professor, Karolinska Institutet, NVS department

Publications and helpful links

General Publications

• Conradsson D, Lofgren N, Stahle A, Hagstromer M, Franzen E. A novel conceptual framework for balance training in Parkinson's disease-study protocol for a randomised controlled trial. BMC Neurol. 2012 Sep 27;12:111. doi: 10.1186/1471-2377-12-111.
• Conradsson D, Lofgren N, Nero H, Hagstromer M, Stahle A, Lokk J, Franzen E. The Effects of Highly Challenging Balance Training in Elderly With Parkinson's Disease: A Randomized Controlled Trial. Neurorehabil Neural Repair. 2015 Oct;29(9):827-36. doi: 10.1177/1545968314567150. Epub 2015 Jan 21.
• Franzen E, Johansson H, Freidle M, Ekman U, Wallen MB, Schalling E, Lebedev A, Lovden M, Holmin S, Svenningsson P, Hagstromer M. 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. BMC Neurol. 2019 Nov 12;19(1):280. doi: 10.1186/s12883-019-1520-2.
• Johansson H, Freidle M, Ekman U, Schalling E, Leavy B, Svenningsson P, Hagstromer M, Franzen E. Feasibility Aspects of Exploring Exercise-Induced Neuroplasticity in Parkinson's Disease: A Pilot Randomized Controlled Trial. Parkinsons Dis. 2020 Mar 25;2020:2410863. doi: 10.1155/2020/2410863. eCollection 2020.
• Freidle M, Johansson H, Ekman U, Lebedev AV, Schalling E, Thompson WH, Svenningsson P, Lovden M, Abney A, Albrecht F, Steurer H, Leavy B, Holmin S, Hagstromer M, Franzen E. Behavioural and neuroplastic effects of a double-blind randomised controlled balance exercise trial in people with Parkinson's disease. NPJ Parkinsons Dis. 2022 Jan 21;8(1):12. doi: 10.1038/s41531-021-00269-5.
• Leavy B, Hagstromer M, Conradsson DM, Franzen E. Physical Activity and Perceived Health in People With Parkinson Disease During the First Wave of Covid-19 Pandemic: A Cross-sectional Study From Sweden. J Neurol Phys Ther. 2021 Oct 1;45(4):266-272. doi: 10.1097/NPT.0000000000000372.
• Johansson H, Ekman U, Rennie L, Peterson DS, Leavy B, Franzen E. Dual-Task Effects During a Motor-Cognitive Task in Parkinson's Disease: Patterns of Prioritization and the Influence of Cognitive Status. Neurorehabil Neural Repair. 2021 Apr;35(4):356-366. doi: 10.1177/1545968321999053. Epub 2021 Mar 10.

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2017
• Primary Completion (Actual): December 13, 2019
• Study Completion (Actual): December 23, 2019

Study Registration Dates

• First Submitted: July 5, 2017
• First Submitted That Met QC Criteria: July 10, 2017
• First Posted (Actual): July 11, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 14, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Exercise; Functional Magnetic Resonance Imaging; Magnetic Resonance Imaging; Balance control
• Additional Relevant MeSH Terms: Synucleinopathies; Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Pathologic Processes; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease; Nervous System Diseases; Gait Disorders, Neurologic; Nerve Degeneration
• Other Study ID Numbers: 4-2872/2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Currently we do not have IRB for sharing.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No