Whole-body Vibration in Children With Neurofibromatosis Type 1

Muscle Weakness Clinical Trial

Official title:

Whole-body Vibration Training Compared to Muscle-strengthening Exercises Alone in Improving Muscle Function in Children With Neurofibromatosis Type 1

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03888248
• Other study ID #: B00472
• Status: Completed
• Phase: N/A
• Start date: July 22, 2019
• Est. completion date: November 30, 2020

Study information

• Verified date: March 2021
• Source: Manchester University NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

It is known that children with NF1 can have weak muscles and suffer from tiredness. It is also known that in similar conditions affecting children's muscles, standing on a vibration device for a few minutes each day can strengthen muscles and improve their ability to perform day-to-day activities. The investigators believe this vibrating platform can be used to strengthen the muscles of children with NF1 also, beyond standard exercises, and therefore allow them to perform day-to-day activities better, do more activity and feel less tired.

If families are keen to take part in this study, the investigators will first need to check they are suitable for the trial. This will be based on the participant's age (6-16 years), their other medical problems that would affect use of the vibration device or tests to assess how effective it is, and their level of muscle weakness.

Once families have agreed to take part, participants will be randomised either to receive a muscle-strengthening exercise session delivered by a physiotherapist that children with weak muscles should continue to perform daily for the next 6 months; or to receive a vibration device to take home and use for a few minutes 5 days a week for 6 months as well as the exercises.

All participants will be invited to attend for a variety of activities and tests, just before starting the trial and 6 months later at the end of the trial to see if there is any benefit from the vibration device. The investigators will repeat these tests again 3 months later, to see if any benefits observed remain, even after the device is removed. They will involve jumping, hopping and balancing on a board, gripping a machine as hard and as long as possible, being fitted with a device that measures activity for 7 days, walking as far as possible for 6 minutes, scanning muscles using MRI, completing a tiredness and general well-being questionnaires, and parents completing a questionnaire of the participant's attention and intellect. The jumping will also be performed 3 months into the study, to see if there is any early improvement in this key test.

All participants will be given full details of what the trial involves before taking part. As with any other trial, participants and their families are free to stop taking part at any time. Although the investigators do not anticipate any safety issues, if any do arise, the families will be asked to contact the trial team.

Description:

Children with neurofibromatosis type 1 (NF1) have been shown in many studies to have reduced muscle mass, strength and function. This could potentially contribute to the fatigue and low quality of life reported in these children. However, to date interventions to improve muscle mass, strength and function in these children have not been established. Whole body vibration (WBV) has been demonstrated to improve walking speed and distance, muscle mass and strength, spasticity and balance in children with other neuromuscular conditions.

In this proposed preliminary matched-pairs interventional trial, the investigators aim to identify whether a home-based WBV therapy programme (9 minutes twice daily for 5 days per week) in addition to standard daily muscle-strengthening exercises improves muscle mass, strength and function over a six month period in children with NF1 aged 6-16 years, compared to daily muscle-strengthening exercises alone. Participants must have evidence of poor muscle strength, with grip force used to assess for this. Key exclusion criteria include significant learning difficulty or autistic spectrum disorder which would create difficulty in use of the WBV device, focal skeletal abnormalities and contraindications to WBV therapy.

The primary outcome measure will be dynamic muscle function using mechanography to measure peak power per kilogram on single two-legged jump.

Secondary/exploratory outcome measures include the 6-minute walk test (to assess lower limb muscle function and mobility), accelerometer data (as a surrogate marker of type and duration of physical activity), hand-held dynamometry (to assess upper limb grip force and endurance), measures on mechanography other than jumping power (to further assess dynamic muscle function), MRI for muscle cross-sectional area and signal intensity, fatigue and general well-being questionnaires and parental reports of attention and cognition.

These measures will be undertaken at baseline, on completion of intervention at 6 months, and again 3 months after to identify whether there is any sustained effect of the intervention following removal. Halfway through the intervention period (3 months), participants will also be invited just to complete the primary outcome of single two-legged jump on ground reaction force plate, as an interim measure.

The investigators hypothesise that WBV therapy will result in increased muscle mass and passive muscle strengthening of the lower limbs, which will translate into better muscle function in the lower limbs compared to baseline data and control group. As it is hypothesised that muscle weakness contributes to the fatigue demonstrated in children with NF1, the investigators would expect to see an improvement in their fatigue scores, which, combined with greater muscle strength, will translate into greater physical activity. The investigators hypothesise that WBV may also have an impact on muscle function in the upper limbs through central sensory stimulation and neuronal rewiring. Many children with NF1 have evidence of attention problems, and the investigators hypothesise that this may improve with WBV, again through central neuronal rewiring.

The trial will be conducted in compliance with this protocol, Good Clinical Practice (GCP) and applicable regulatory requirements.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: November 30, 2020
• Est. primary completion date: November 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 16 Years

Eligibility

Inclusion Criteria:

• Neurofibromatosis Type 1 (confirmed by NIH consensus criteria)

• Grip force less than -1 SDS according to age- and gender-matched normative data

Exclusion Criteria:

• Focal skeletal abnormalities (pseudoarthrosis, kyphoscoliosis likely to require surgery, known spondylolisthesis)

• Significant autistic spectrum disorder or learning difficulties (neurodevelopmental age less than 6 years)

• Inability to adequately weight-bear or balance on vibrating platform

• Lower limb plexiform causing limb length discrepancy

• Contraindications to use of whole-body vibration device (acute thrombosis, implants in activated regions of the body, acute inflammation of the locomotor system, herniae, propensity to fragility fractures or fracture within the past 3 months, history of renal calculi, epilepsy)

Related Conditions & MeSH terms

• Muscle Weakness
• Neurofibroma
• Neurofibromatoses
• Neurofibromatosis 1
• Neurofibromatosis Type 1
• Paresis

Intervention

Device:
• Whole-body vibration
Home-based whole-body vibration therapy by standing on Galileo Med 15 platform for 9 mins twice a day for 5 days per week

Other:
• Muscle strengthening exercises
Daily muscle strengthening exercises to be performed at home following a group education session by paediatric physiotherapist

Locations

Country	Name	City	State
United Kingdom	Manchester University Hospitals NHS Foundation Trust	Manchester

Sponsors (2)

Lead Sponsor	Collaborator
Manchester University NHS Foundation Trust	Manchester Metropolitan University

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Peak force (newtons) per kilogram on multiple one-legged hop using Leonardo Mechanography Ground Reaction Force Plate		Baseline, 6 months, 9 months
Other	Efficiency of single two-legged jump using Leonardo Mechanography Ground Reaction Force Plate	Efficiency is calculated by the Leonardo software by comparing peak force and peak power, and is an indicator of movement velocity and co-ordination. The software will automatically calculate z-score (based on weight, age and gender), which will be used for analysis	Baseline, 6 months, 9 months
Other	Balance tasks	Most complex balance task that can be performed for 10 seconds will be recorded (increasing in complexity from Romberg stance, to semi-tandem stance, to tandem stance, to balancing on one foot). This will be performed on Leonardo Mechanography Ground Reaction Force Plate	Baseline, 6 months, 9 months
Other	Path length using Leonardo Mechanography Ground Reaction Force Plate	Path length in centimetres of the completed balance tasks	Baseline, 6 months, 9 months
Other	Ellipse area using Leonardo Mechanography Ground Reaction Force Plate	Ellipse area in centimetres squared of the completed tasks	Baseline, 6 months, 9 months
Other	Maximal hand grip force	Maximal hand grip force (newtons) using hand-held dynamometry	Baseline, 6 months, 9 months
Other	Sustained grip force	Sustained grip force (newtons) over 10 seconds using hand-held dynamometry	Baseline, 6 months, 9 months
Other	Magnetic resonance imaging of right calf muscle	Cross-sectional area in centimetres squared of calf muscles in right leg	Baseline, 6 months, 9 months
Other	Magnetic resonance imaging of right mid-thigh muscle	Cross-sectional area in centimetres squared of mid-thigh muscles in right leg	Baseline, 6 months, 9 months
Other	Magnetic resonance imaging - signal intensity	Average signal intensity of right leg muscle on MRI	Baseline, 6 months, 9 months
Other	Child Outcome Rating Scale	Total score from non-validated visual analog scale of participant's perception of lifestyle and well-being. This will assess participant's perception of 6 domains: 'Mood and emotional well-being', 'Tiredness/fatigue', 'Hobbies/interests/activities', 'School', 'Attention/concentration' and ''Overall'. Each domain is on a 10cm rule, therefore total score can range from 0 to 60. A higher score indicates better well-being (i.e. better outcome).	Baseline, 6 months, 9 months
Other	Conners Parent Rating Scale	Total score on validated questionnaire for parental report of attention deficit hyperactivity disorder (ADHD) symptomatology, within domains of 'Inattention', 'Hyperactivity/impulsivity', 'Learning problems', 'Executive functioning', 'Aggression' and 'Peer relations'. There are 45 questions, each rated on a scale of 0 to 3 (therefore total score can range from 0 to 135). A higher score indicates greater features of ADHD (i.e. worse outcome).	Baseline, 6 months, 9 months
Other	Persistence of changes in primary outcome on withdrawal of intervention	Change from baseline to 9 months (i.e. 3 months after withdrawal of intervention) of peak power (in watts) per kilogram of single two-legged jump using Leonardo Mechanography Ground Reaction Force Plate	Baseline, 9 months
Other	Evidence of early changes in primary outcome	Change from baseline to 3 months (i.e. half way through intervention) of peak power (in watts) per kilogram of single two-legged jump using Leonardo Mechanography Ground Reaction Force Plate	Baseline, 3 months
Primary	Change in peak power per kilogram on single two-legged jump using Leonardo Mechanography Ground Reaction Force Plate	Change from baseline to 6 months of peak power per kilogram of single two-legged jump using Leonardo Mechanography Ground Reaction Force Plate. Power will be measured in watts.	Baseline, 6 months
Secondary	6 minute walk test	Distance in metres walked during 6 minutes	Baseline, 6 months, 9 months
Secondary	Accelerometer (duration)	Duration of activity in minutes over 7 days using accelerometer	Baseline, 6 months, 9 months
Secondary	Accelerometer (intensity)	Intensity of activity (accelerometer counts per minute) over 7 days using accelerometer	Baseline, 6 months, 9 months
Secondary	PedsQL Multi-dimensional Fatigue Scale	Total score from age-appropriate validated questionnaire that asks for perceived fatigue within the domains of 'General', 'Sleep/Rest' and 'Cognitive'. Each domain consists of 6 questions, with participants/parents rating each question from 0 to 4 (therefore total score can range from 0 to 72). A higher total score indicates greater fatigue (i.e. worse outcome)	Baseline, 6 months, 9 months