Motor-cognitive Performance in People With Multiple Sclerosis

Multiple Sclerosis Clinical Trial

— HiBalance-MS  

Official title:

Motor-cognitive Performance in People With Multiple Sclerosis - Brain Activity and Effects of Balance Exercise

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06312046
• Other study ID #: 2018 374-31
• Status: Recruiting
• Phase: N/A
• Start date: February 26, 2024
• Est. completion date: August 31, 2027

Study information

• Verified date: March 2024
• Source: Karolinska Institutet
• Contact: Compliance Office Karolinska Institutet
• Phone: +46852480000
• Email: compliance[@]ki.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Having a neurological disease such as multiple sclerosis (MS) leads to difficulties in balance and gait with or without concurrent performance of cognitive tasks, hindering activity performance and influencing the possibilities for an independent lifestyle.

The investigators have adapted a previously developed balance training program to a highly challenging program specifically directed to MS (HiBalance-MS). This program was recently tested and found feasible in a pilot study. The investigators will now perform a randomized controlled trial in people with MS, in order to determine the effects of the program. The hypothesis is that progressively challenging balance exercise programs that are specific to the balance control domains affected by MS will be effective to improve balance control, walking, motor-cognitive performance, activity performance and health related quality of life.

Description:

Everyday living means being in complex environments and performing complex activities which usually consist of and require a combination of motor and cognitive skills. Having a neurological disease such as multiple sclerosis (MS) compromises the motor-cognitive performance. This leads to difficulties in balance and gait with or without concurrent performance of cognitive tasks, hindering activity performance and influencing the possibilities for an independent lifestyle.

The investigators have, in a co-design process with stakeholders, adapted a HiBalance program, originally developed by the Franzén research group for people with Parkinson's disease and combining motor-cognitive exercises in a progressively more difficult manner (HiBalance-PD), to a program specifically developed to MS (HiBalance-MS). The developed HiBalance-MS program was recently tested and found feasible in a pilot study (results published 2023). The investigators will now perform a randomized controlled trial in people with MS, in order to determine the effects of a highly challenging balance training program (HiBalance-MS) on physical and cognitive functioning, and activity performance, in this group. The results will have immediate application and clinical relevance. With improved balance control people with MS will also gain other health benefits related to an active lifestyle and a better everyday life.

The hypothesis that motor-cognitive performance is reduced and impact activity performance in people with MS. They also hypothesize that progressively challenging balance exercise programs that are specific to the balance control domains affected by MS will be effective to improve balance control, walking, motor-cognitive performance, activity performance and health related quality of life.

Participants will be recruited through Karolinska University Hospital, through physiotherapists and physicians specialized in neurology in Stockholm and via advertisement in newspapers and the patient organization NEURO Sweden. 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 HiBalance-MS program is based on scientifically well-established principles of exercise training and postural control. It will be conducted as a progressive individually adjusted group training to challenge the specific balance deficit of every participant. Four main sub-systems underlying balance control (stability limits, anticipatory postural adjustments, sensory integration and motor agility) are used to target specific balance impairments. To ensure highly challenging exercises, each task is individually adjusted. Daily variation in capacity will be rated before each training session and participants will at the end of each session rate the challenging level. The training will be performed in the clinic (Karolinska University hospital) for an hour, twice a week for 10 weeks, as a group intervention (6 to 8 participants) facilitated by two physiotherapists/trainers.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: August 31, 2027
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• an MS diagnosis according to McDonald criteria;

• an overall MS-disability score from 2.0 to 5.5 according to the Expanded Disability Status Scale;

• ability to walk 100 m without aid;

• a maximum score of 24 in the Mini-BESTest (i.e., < 25 points)

• 18 to 65 years of age

Exclusion Criteria:

• cognitive impairment as indicated by a score <21 in the Montreal Cognitive Assessment;

• presence of other conditions that would substantially influence balance;

• an MS relapse or change of disease-modifying treatment within the past 8 weeks

Related Conditions & MeSH terms

• Multiple Sclerosis
• Postural Balance
• Sclerosis

Intervention

Other:
• HiBalance-MS
See arm description for intervention group.

Locations

Country	Name	City	State
Sweden	Karolinska Institutet	Stockholm

Sponsors (2)

Lead Sponsor	Collaborator
Karolinska Institutet	Karolinska University Hospital

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mini Balance Evaluation Systems test.	Balance performance. A rating scale for dynamic balance incorporating 14 different balance and gait items that are assessed by a physical therapist on a scale from 0-2. Points between 0 and 28; a higher total score indicates better balance control.	Pre intervention baseline and post intervention at 10 weeks.
Secondary	10-Meter Walk Test, maximum speed.	Gait performance. Maximum gait speed (meter/second), a higher score indicates higher gait speed.	Pre intervention baseline and post intervention at 10 weeks.
Secondary	10-Meter Walk Test, self-selected speed.	Gait performance. Self-selected comfortable gait speed (meter/second), a higher score indicates higher self-selected comfortable gait speed.	Pre intervention baseline and post intervention at 10 weeks.
Secondary	2-Minute Walk Test, self-selected speed.	Gait performance. Self-selected gait speed (meter/second), a higher score indicates higher self-selected endurance gait speed.	Pre intervention baseline and post intervention at 10 weeks.
Secondary	Gait speed during simultaneous dual task performance.	Gait speed (meter/second), will be analyzed during dual task walking with the Ambulatory Parkinson´s Disease Monitoring (APDM) mobility Lab system. Dual tasking during walking will be performed with the Auditory stroop task, a test of cognitive function, see below. A higher score indicates higher gait speed during dual tasking,	Pre intervention baseline and post intervention at 10 weeks.
Secondary	Stride length during dual task gait performance.	Stride length (meter) during gait will be analyzed during dual task walking with the Ambulatory Parkinson´s Disease Monitoring (APDM) mobility Lab system. Dual tasking during walking will be performed with the Auditory stroop task, a test of cognitive function, see below.Longer stride length indicates better control during walking,	Pre intervention baseline and post intervention at 10 weeks.
Secondary	Step time during dual task gait performance.	Step time during gait (seconds) will be analyzed during dual task walking with the Ambulatory Parkinson´s Disease Monitoring (APDM) mobility Lab system. Dual tasking during walking will be performed with the Auditory stroop task, a test of cognitive function, see below. Shorter step time indicates better control during walking,	Pre intervention baseline and post intervention at 10 weeks.
Secondary	Response errors in dual task cognitive performance	Dual task cognitive performance during walking will be performed with the Auditory stroop task, a test of cognitive flexibility in selective executive functions. Cognitive performance of the dual task will be assessed as errors in the response (numbers) to the Auditory stroop task. Data colllection is performed through wireless headphones (RazerTM ManO'War) using Audacity software (version 3.0.2).	Pre intervention baseline and post intervention at 10 weeks.
Secondary	Reaction time in dual task cognitive performance	Dual task cognitive performance during walking will be performed with the Auditory stroop task, a test of cognitive flexibility in selective executive functions. Cognitive performance of the dual task will be assessed as reaction time (seconds) in the Auditory stroop task. Data colllection is performed through wireless headphones (RazerTM ManO'War) using Audacity software (version 3.0.2).	Pre intervention baseline and post intervention at 10 weeks.
Secondary	Six-Spot Step Test.	A test of complex walking. The Six-Spot Step Test is a 5 meter test-field criss-cross walk pattern where the subject while walking is simultaneously kicking wooden blocks from marked circles in the field. Mean time (seconds) of four trials is calculated, shorter time indicates better complex walking performance.	Pre intervention baseline and post intervention at 10 weeks.
Secondary	Completion time in the Trail Making Test.	The Trail Making Test (from Delis-Kaplan Executive Function System) assesses attention and psychomotor processing speed. The time (seconds) to complete the test, connecting numbers and letters correctly, is registered. Shorter completion time indicates better attention and higher psychomotor processing speed.	Pre intervention baseline and post intervention at 10 weeks.
Secondary	Number of errors in the Trail Making Test.	The Trail Making Test (from Delis-Kaplan Executive Function System) assesses attention and psychomotor processing speed. The number of mistakes/errors is registered. Less number of mistakes/errors indicates better attention and higher psychomotor processing speed.	Pre intervention baseline and post intervention at 10 weeks.
Secondary	Immediate and delayed recall in the Ray Auditory Verbal Learning Test.	The Ray Auditory Verbal Learning Test assesses episodic memory. In this test 15 words is repeatedly (five times) read for the subject. The subject is asked to recall as many as possible. The subject is asked again after 30 minutes to recall as many words as possible. The test assesses immediate recall (number) and delayed recall (number) of words where higher number of immediate and delayed recalled words indicates better episodic memory.	Pre intervention baseline and post intervention at 10 weeks.
Secondary	Cognitive processing speed in the Symbol Digit Modalities Test.	The Symbol Digit Modalities Test assesses cognitive processing speed. The subject is asked to pair specific numbers with given symbols. The number of correctly paired numbers and symbols within 90 seconds is registered where a higher number indicates higher cognitive processing speed.	Pre intervention baseline and post intervention at 10 weeks.
Secondary	Cognitive function - composite measure of three cognitive tests.	Cognitive function will also be assessed as a composite measure of a cognitive test battery consisting of: Trail making Test (from Delis-Kaplan Executive Function System), testing attention and and psychomotor processing speed); Ray Auditory Verbal Learning Test, assessment of episodic memory; and Symbol Digit Modalities Test, assessment of cognitive processing speed. First, the scores of each of the three tests will be standardised into z-scores using pre-scores. Models using different test are compared. The model including all three tests and using the robust diagonally weighted least square estimation will be chosen based on fit values. Last, the z-scores of each test and person are 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.
Secondary	Physical activity level.	Assessment with accelerometer Actigraph GT3X+. Participants wear the accelerometer around the hip, attached slightly above the iliac crest with an elastic band. They wear the accelerometer in their daily life for seven consecutive days (minimum four days), only removing it when showering, bathing, swimming, and at night. As a proxy for the level of daily physical activity, the number of steps per day will be used, where a higher number indicates higher level of physical activity.	Pre-and-post-intervention over four to seven days when awake.
Secondary	Physical activity level, self-reported.	Frändin & Grimby Scale, a self-reported questionnaire (score 1-6, higher score = higher physical activity level measured in hours,	Pre intervention baseline and post intervention at 10 weeks.
Secondary	Physical exercise habits, self-reported.	A question regarding physical exercise habits is included (from The Swedish Research Council). Score 1-6, A higher score indicates larger interval of minutes per week used for physical exercise.	Pre intervention baseline and post intervention at 10 weeks.
Secondary	The generic Walk-12 questionnaire.	Self assessment of walking ability with the generic Walk-12 questionnaire. A total of 12 questions, possibility to score from 1 to 5. Total score between12 and 60. A higher score indicates perceived more limited walking ability.	Pre intervention baseline and post intervention at 10 weeks.
Secondary	Falls Efficacy Scale - International.	A self-reported questionnaire regarding falls efficacy, A total of 16 questions, score 1-4. Total score from 16 to 64 points, a higher total score = more concerned of falling.	Pre intervention baseline and post intervention at 10 weeks.
Secondary	Assesment of anxiety with the Hospital Anxiety and Depression Scale.	A self-reported questionnaire assessing anxiety and depression. Total score from 0 to 28 points, 14 points each on the depression and anxiety parts respectively. Lower scores on the anxiety part indicates less anxiety.	Pre intervention baseline and post intervention at 10 weeks.
Secondary	Assesment of depression with the Hospital Anxiety and Depression Scale.	A self-reported questionnaire assessing anxiety and depression. Total score from 0 to 28 points, 14 points each on the depression and anxiety parts respectively. Lower scores on the depression part indicates less depression.	Pre intervention baseline and post intervention at 10 weeks.
Secondary	Modified Fatigue Impact Scale.	A self-reported questionnaire which measures impact of fatigue on physical, cognitive and psychosocial functioning, The scale consists of 21 items, scored from 0 to 4. Total score ranges from 0 to 84 points. Higher scores indicate larger impact of fatigue (total impact or impact in physical, cognitive and psychosocial functioning.	Pre intervention baseline and post intervention at 10 weeks.
Secondary	Occupational Gap Questionnaire.	A self-reported questionnaire measuring participation in everyday activities. The questionnaire includes 30 questions regarding if an activity is performed and regarding if the person wants to perform the activity. Number of activities performed (higher scores = better) and number of wanted but not performed activities (higher scores = worse) are counted .	Pre intervention baseline and post intervention at 10 weeks.
Secondary	Acceptance of Chronic Health Condition scale.	A self-reported questionnaire (10 questions scored on a 5 category Likert rating scale measuring acceptance of chronic health condition. Scores from 1 to 50), a higher score = higher level of acceptance.	Pre intervention baseline and post intervention at 10 weeks.
Secondary	Multiple Sclerosis Impact Scale - physical impact.	A self-reported diagnose-specific questionnaire assessing health-related quality of life. A total of 29 items (20 physical and 9 psychological). Items are rated from 1 to 5. Total score ranges from 20 to 100 in physical impact. Higher total score = worse physical impact.	Pre intervention baseline and post intervention at 10 weeks.
Secondary	Multiple Sclerosis Impact Scale - psychological impact.	A self-reported diagnose-specific questionnaire assessing health-related quality of life. A total of 29 items (20 physical and 9 psychological). Items are rated from 1 to 5. Total scores range from 9 to 45 in psychological impact. Higher total score = worse psychological impact.	Pre intervention baseline and post intervention at 10 weeks.
Secondary	Euroqol-5 Dimensions-5 Level (EuroQoL-5D-5L).	A self-reported generic questionnaire measuring health-related quality of life. The questionnaire assesses five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels - higher level score = increased disability.	Pre intervention baseline and post intervention at 10 weeks.
Secondary	Euroqol Visual Analogue Scale (EQ VAS).	A self-reported generic questionnaire measuring health-related quality of life. In addition to the five dimensions of health (as described above) the EuroQoL-5D-5L includes a vertical visual analogue scale (the EQ VAS), which records the patient's self-rated health on the vertical visual analogue scale where the endpoints are labelled 'Best imaginable health state' (100) and 'Worst imaginable health state' (0).	Pre intervention baseline and post intervention at 10 weeks.
Secondary	World Health Organization Disability Assessment Schedule, version 2.0. (WHODAS 2.0)	A self-reported questionnaire consisting of 12 questions assessing disability. Total score from12 to 60, a higher score = worse disability.	Pre intervention baseline and post intervention at 10 weeks.

External Links

•   Publication: A highly challenging balance training intervention for people with multiple sclerosis: a feasibility trial