Whole-body Vibration in Children With Neurofibromatosis Type 1
Condition: Neurofibromatosis Type 1; Muscle Weakness
MeSH terms: Neurofibromatoses; Neurofibromatosis 1; Neurofibroma; Muscle Weakness; Paresis
Study type: Interventional

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.
    

Detailed 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.
    

Intervention name(s): Whole-body vibration; Muscle strengthening exercises
Intervention type(s): Device; Other
Intervention description(s): Home-based whole-body vibration therapy by standing on Galileo Med 15 platform for 9 mins twice a day for 5 days per week; Daily muscle strengthening exercises to be performed at home following a group education session by paediatric physiotherapist
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Neurofibromatosis Type 1; Whole-body vibration; Muscle weakness