<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02982343</url>
  </required_header>
  <id_info>
    <org_study_id>16/LO/0720</org_study_id>
    <nct_id>NCT02982343</nct_id>
  </id_info>
  <brief_title>BALTiC Study: A Feasibility Analysis of Home Based BALance Training in People With Charcot-Marie-Tooth Disease</brief_title>
  <acronym>BALTiC</acronym>
  <official_title>BALTiC Study: A Feasibility Analysis of Home Based BALance Training in People With Charcot-Marie-Tooth Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University College London Hospitals</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Charcot Marie Tooth United Kingdom</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Kingston University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University College London Hospitals</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Charcot Marie Tooth (CMT) is the most common inherited neuropathy. It affects the nerves of&#xD;
      the hands and feet first, slowly progressing towards the centre of the body. It causes&#xD;
      varying degrees of weakness and reduced feeling, usually affecting the feet and ankles first.&#xD;
      High incidence of falls and knock on effects in quality of life are common. This is a&#xD;
      lifelong condition which, though not life limiting, does not have a cure. Research into the&#xD;
      effect of balance rehabilitation in people with CMT has been limited to traditional&#xD;
      exercises, which do not address the complex nature of balance impairments in this condition.&#xD;
      Multi-sensory rehabilitation has proved beneficial in improving balance in people with&#xD;
      sensory neuropathy. Research shows that strengthening trunk muscles can improve balance in&#xD;
      older people. Trunk and muscles close to it are largely unaffected in people with CMT,&#xD;
      therefore these muscles could be strengthened in these patients. This study proposes to&#xD;
      assess the feasibility of multi-sensory balance training, strength training with a focus on&#xD;
      the trunk and muscles close to the trunk, and falls management education. This comprehensive&#xD;
      approach is reflective of a clinical physiotherapy programme. Though a life-long condition,&#xD;
      many people with CMT lead full lives. A home based programme is proposed to so that patients&#xD;
      can fit it into their lives without having to travel for treatment. Therapists will use&#xD;
      self-management principles within treatment. Measurements will be taken prior to and&#xD;
      following treatment including physical measures, questionnaires and interviews. The&#xD;
      physiotherapy interventions will be taught home and data collection will be at the National&#xD;
      Hospital for Neurology and Neurosurgery, University College London Hospitals (UCLH).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A recent, unpublished focus group study of people with CMT found that they reported more&#xD;
      falls than healthy people. They reported problems walking on uneven surfaces, difficulty&#xD;
      getting off the floor and a necessity to consciously think about every step to avoid falling&#xD;
      while walking (GM Ramdharry et al., 2015). A retrospective survey of people with CMT found&#xD;
      that 89% of the 94 respondents reported falls to the ground. Half of them reported falling at&#xD;
      least once a month with 5% falling every day (Ramdharry et al., 2011). We have just completed&#xD;
      an exploratory study of factors predicting falls risk. Preliminary analysis of prospective&#xD;
      falls data for 32 people over 6 months showed that they fell a median of 4 times (range 0 -&#xD;
      54 falls) and functional balance performance may be predictive (Ramdharry et al., 2015). A&#xD;
      study of people with CMT1a found that sensory impairment increased visual dependence for a&#xD;
      static balance task (van der Linden et al., 2010). There has only been one small study of&#xD;
      balance training in people with CMT, comparing a novel rehabilitation device with more&#xD;
      traditional exercises (Matjacić and Zupan, 2006). Both interventions showed improvement in&#xD;
      functional balance scores. Studies of proximal strength training in CMT have shown&#xD;
      improvements in walking parameters (Chetlin et al., 2004; Lindeman et al., 1995), but the&#xD;
      effect on balance has not been explored. Because of the mixed sensori-motor presentation of&#xD;
      people with CMT, a combined approach of multi-sensory balance training and proximal&#xD;
      strengthening will be delivered. A home-based model has been proposed as CMT is a life-long&#xD;
      condition that needs to be managed by the individual outside of the medical or therapy&#xD;
      environment.&#xD;
&#xD;
      STUDY DESIGN &amp; JUSTIFICATION A single blinded randomised controlled design has been chosen in&#xD;
      this feasibility study. The intention is to see if there is an effect of the intervention to&#xD;
      later be explored in a larger randomized controlled trial. A blinded assessor will measure&#xD;
      balance performance prior to randomisation and following the 12 weeks of either intervention&#xD;
      or control. They will also undertake qualitative interviews prior to randomization and&#xD;
      following final measurement session. Interviews will inform the intervention and its&#xD;
      acceptability. All participants will receive a falls assessment and falls education.&#xD;
      Following randomisation, participants will either receive the 12-week intervention or control&#xD;
      period. The intervention will include a holistic programme of physiotherapy including&#xD;
      strength training of muscle groups unaffected by the condition and multi-sensory exercises to&#xD;
      target balance. The program will be delivered by a physiotherapist trained in delivering&#xD;
      treatment under the principles of self-management. Exercises will be carried out by the&#xD;
      patients in their own homes and monitored by the research physiotherapist, progressing as&#xD;
      appropriate. Those randomized to the control arm will receive monitoring telephone calls&#xD;
      throughout this 12-week period.&#xD;
&#xD;
      RECRUITMENT Patients will be recruited from outpatient neurology clinics at Queen Square&#xD;
      which specialise in the diagnosis and management of CMT. Patients who fit the inclusion&#xD;
      criteria will be approached and the trial will be described to them. Written information will&#xD;
      be provided and arrangement made for a way to make contact once they have decided about&#xD;
      whether they wish to proceed with screening. All patients who agree to proceed will go&#xD;
      through a screening which will take place over the telephone. Those who pass screening will&#xD;
      be provided with falls diary postcards or arrangement for falls diary emails, which they will&#xD;
      be asked to monitor and report for one month. A sample will be invited for a qualitative&#xD;
      interview. Arrangement will be made for them to attend a baseline measurement session, falls&#xD;
      assessment, and falls education following the month-long falls monitoring.&#xD;
&#xD;
      Measures will include:&#xD;
&#xD;
      Patient reported questionnaires of balance confidence, mood, walking ability and physical&#xD;
      functioning 10m walk test / 6 minute walk test Berg Balance Scale Bruininks Oseretsky Test&#xD;
      (BOT) BESTest Functional balance tests using force plate and movement analysis equipment&#xD;
      Strength testing of the lower limbs and hands Charcot Marie Tooth Examination Score (CMTES) A&#xD;
      block randomisation will occur following the baseline measurement and falls education session&#xD;
      with allocation either being to a control arm or an intervention arm. This will be done by&#xD;
      the PI or research physiotherapist who will remain un-blinded. Contact with the blinded&#xD;
      assessor will cease until the final measurement session 12 weeks later.&#xD;
&#xD;
      INTERVENTION:&#xD;
&#xD;
      If randomised to the control arm of the study, participants will be advised that the research&#xD;
      physiotherapist will contact them monthly to monitor any falls or issues. For those&#xD;
      randomised to the intervention arm, a home visit will be arranged with the research&#xD;
      physiotherapist as soon as possible. During this session, the research physiotherapist will&#xD;
      provide the participant with exercises to strengthen the muscles of the trunk and proximal&#xD;
      muscles using body weight and graded ankle weights. Strength training will be performed 4&#xD;
      times per week. They will also give a selection of exercises targeting balance to challenge&#xD;
      stability and sensory feedback. Participants will be asked to perform balance exercises&#xD;
      daily. A risk assessment will be undertaken with guidance on how to ensure safety when doing&#xD;
      the exercises. An exercise diary will be provided for the participants to monitor exercise&#xD;
      frequency.&#xD;
&#xD;
      Arrangements will be made for weekly telephone calls with the research physiotherapist to&#xD;
      monitor progress and a provisional date set for the first monthly home monitoring visit.&#xD;
      Participants in the intervention arm will be contacted weekly for 12 weeks on the study. The&#xD;
      research physiotherapist will visit them at home to monitor and progress exercises once a&#xD;
      month during this time.&#xD;
&#xD;
      QUALITATIVE RESEARCH At the consent meeting all patients will be invited to take part in&#xD;
      interviews conducted after the consent meeting and following completion of the final&#xD;
      measurements. They will be made aware that participation in the interviews is supplementary&#xD;
      to the main study and they are free to decline. Purposive sampling will be used to ensure a&#xD;
      sample of maximum diversity of age, gender, and symptom severity. Potential qualitative&#xD;
      interview participants will be given written details of the qualitative study and asked to&#xD;
      give their consent to be interviewed if they are willing to take part. The interview will be&#xD;
      audio recorded and consist of a dialogue between the interviewer (the researcher) and the&#xD;
      participant. A topic guide will be used during the interviews, but the participant will be&#xD;
      invited to raise issues of importance to them. Data analysis will be iterative, in that it&#xD;
      will be continually analysed throughout the data collection process and used to inform&#xD;
      following interviews.&#xD;
&#xD;
      PROCEDURES TO DEAL WITH RESEARCHER EFFECTS AND BIAS Assessments will be carried out by a&#xD;
      blinded assessor to standardise treatment during tests. Falls assessment and falls education&#xD;
      will be provided at the baseline measurement session by the blinded assessor, prior to&#xD;
      participant randomisation. In this way participants will be given the same treatment. The&#xD;
      blinded assessor will perform final measurements. The participant will be reminded prior to&#xD;
      the start the final session to not mention what they may or may not have been doing in the 12&#xD;
      weeks prior to maintain blinding throughout the session&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2016</start_date>
  <completion_date type="Actual">March 2018</completion_date>
  <primary_completion_date type="Actual">March 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Balance performance</measure>
    <time_frame>12 weeks</time_frame>
    <description>Balance performance will be measured using laboratory measures of postural stability during static and dynamic tasks. Centre of pressure excursion and velocity will be the main variables</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Recruitment rate</measure>
    <time_frame>1 year</time_frame>
    <description>For this feasibility study, recruitment rate data will be gathered</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Falls monitoring</measure>
    <time_frame>20 weeks</time_frame>
    <description>Falls monitoring will be done one month before, during the 12 week invention/control period and one month afterwards using postcards or a web based app, depending on participant preference.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bruininks Oseretsky Test (BOT)</measure>
    <time_frame>12 weeks</time_frame>
    <description>Clinician rated measure of functional balance performance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Berg Balance test</measure>
    <time_frame>12 weeks</time_frame>
    <description>Clinician rated measure of functional balance performance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BESTest</measure>
    <time_frame>12 weeks</time_frame>
    <description>Clinician rated measure of functional balance performance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>10 minute timed walk</measure>
    <time_frame>12 weeks</time_frame>
    <description>Walking speed test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantitative lower limb muscle strength testing</measure>
    <time_frame>12 weeks</time_frame>
    <description>Hand-held myometry protocol performed by rater for the major lower limb muscle groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CMTES: Charcot Marie Tooth Examination Score</measure>
    <time_frame>12 weeks</time_frame>
    <description>Clinician rated disease severity scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Falls Self Efficacy Scale</measure>
    <time_frame>12 weeks</time_frame>
    <description>Patient reported outcome measure of balance confidence. Questionnaire.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Walk-12</measure>
    <time_frame>12 weeks</time_frame>
    <description>Patient reported outcome measure of walking function. Questionnaire.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>IPAQ: International Physical Activity Questionnaire</measure>
    <time_frame>12 weeks</time_frame>
    <description>Patient reported outcome measure of physical activity. Questionnaire.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SF36: Short Form 36</measure>
    <time_frame>12 weeks</time_frame>
    <description>Patient reported outcome measure of health related quality of life. Questionnaire.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital Anxiety and Depression Score</measure>
    <time_frame>12 weeks</time_frame>
    <description>Patient reported outcome measure of depression and anxiety symptoms. Questionnaire.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Charcot-Marie-Tooth Disease, Type IA</condition>
  <arm_group>
    <arm_group_label>Falls management plus exercise training</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Falls management and education session. Home proximal lower limb strength training and multi-sensory balance training.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Falls management only</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Falls management and education session only.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Falls management plus exercise training</intervention_name>
    <description>Participants will undergo a session of falls management and education followed by 12 weeks of strength and balance training. Strength training will be performed 4 times per week. Resistance training of the proximal muscles will be prescribed progressing to loads of 60% of 1 repetition maximum, 8-12 repetitions. Weaker muscles will be trained using 2 sets of 8-12 repetitions against gravity. They will also give a selection of exercises targeting balance to challenge stability and sensory feedback using equipment such as foam cushions, though will be individual based on participants' limitations and abilities. Participants will be asked to perform balance exercises daily.</description>
    <arm_group_label>Falls management plus exercise training</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Falls management only</intervention_name>
    <description>Participants will undergo a session of falls management and education.</description>
    <arm_group_label>Falls management only</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Genetically confirmed diagnosis of CMT1a&#xD;
&#xD;
          2. History of falls&#xD;
&#xD;
          3. Mixed sensory and motor presentation&#xD;
&#xD;
          4. Over 18 years&#xD;
&#xD;
          5. Able to stand unsupported for five minutes&#xD;
&#xD;
          6. Able to walk for 50m with or without a walking stick or orthotic devices&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Presence of other significant neurological disorders (such as multiple sclerosis,&#xD;
             cerebrovascular diseases, epilepsy, movement disorders), or major comorbidities (e.g.&#xD;
             vestibular dysfunction, use of medication which may affect balance, cognitive&#xD;
             impairment, presence of medical conditions in which exercise training may be&#xD;
             detrimental).&#xD;
&#xD;
          2. Presence of peripheral neuropathy caused by a condition other then CMT.&#xD;
&#xD;
          3. Limb surgery during the six months prior to screening (or planned before final&#xD;
             assessment).&#xD;
&#xD;
          4. Participation in any other concurrent intervention trial, or less than six months&#xD;
             after cessation of an intervention trial.&#xD;
&#xD;
          5. Women of child-bearing age if they are pregnant, planning a pregnancy during their&#xD;
             time in the study or in the 12 weeks following giving birth. This is due to the&#xD;
             effects of pregnancy on balance.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gita M Ramdharry, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University College London Hosptials NHS Trust</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Hospital for Neurology and Neurosurgery, UCLH</name>
      <address>
        <city>London</city>
        <zip>WC1N 3BG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Ramdharry, G., M. Dudziec, D. Tropman, E. Dewar, A. Wallace, M. Laura, R. Grant, and M. Reilly. 2015. 'Exploring the Causes of Falls and Balance Impairments in People with Charcot-Marie Tooth Disease'. Physiotherapy 101 (May): e1255. doi:10.1016/j.physio.2015.03.1159.</citation>
  </reference>
  <reference>
    <citation>Ramdharry GM, Pollard A, Anderson C, Laura M, Murphy SM, Dudziec M, Dewar EL, Hutton E, Grant R, Reilly MM. A pilot study of proximal strength training in Charcot-Marie-Tooth disease. J Peripher Nerv Syst. 2014 Dec;19(4):328-32. doi: 10.1111/jns.12100.</citation>
    <PMID>25582960</PMID>
  </reference>
  <reference>
    <citation>van der Linden MH, van der Linden SC, Hendricks HT, van Engelen BG, Geurts AC. Postural instability in Charcot-Marie-Tooth type 1A patients is strongly associated with reduced somatosensation. Gait Posture. 2010 Apr;31(4):483-8. doi: 10.1016/j.gaitpost.2010.02.005. Epub 2010 Mar 11.</citation>
    <PMID>20226674</PMID>
  </reference>
  <reference>
    <citation>Matjacic Z, Zupan A. Effects of dynamic balance training during standing and stepping in patients with hereditary sensory motor neuropathy. Disabil Rehabil. 2006 Dec 15;28(23):1455-9. doi: 10.1080/09638280600646169.</citation>
    <PMID>17166808</PMID>
  </reference>
  <reference>
    <citation>Chetlin RD, Gutmann L, Tarnopolsky M, Ullrich IH, Yeater RA. Resistance training effectiveness in patients with Charcot-Marie-Tooth disease: recommendations for exercise prescription. Arch Phys Med Rehabil. 2004 Aug;85(8):1217-23. doi: 10.1016/j.apmr.2003.12.025.</citation>
    <PMID>15295743</PMID>
  </reference>
  <reference>
    <citation>Lindeman E, Leffers P, Spaans F, Drukker J, Reulen J, Kerckhoffs M, Koke A. Strength training in patients with myotonic dystrophy and hereditary motor and sensory neuropathy: a randomized clinical trial. Arch Phys Med Rehabil. 1995 Jul;76(7):612-20. doi: 10.1016/s0003-9993(95)80629-6.</citation>
    <PMID>7605179</PMID>
  </reference>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>November 28, 2016</study_first_submitted>
  <study_first_submitted_qc>November 30, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 5, 2016</study_first_posted>
  <last_update_submitted>May 2, 2018</last_update_submitted>
  <last_update_submitted_qc>May 2, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University College London Hospitals</investigator_affiliation>
    <investigator_full_name>Gita Ramdharry</investigator_full_name>
    <investigator_title>Principle Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tooth Diseases</mesh_term>
    <mesh_term>Charcot-Marie-Tooth Disease</mesh_term>
    <mesh_term>Nerve Compression Syndromes</mesh_term>
    <mesh_term>Hereditary Sensory and Motor Neuropathy</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02982343
org study id: 16/LO/0720
nct id: NCT02982343
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
Charcot Marie Tooth (CMT) is the most common inherited neuropathy. It affects the nerves of
      the hands and feet first, slowly progressing towards the centre of the body. It causes
      varying degrees of weakness and reduced feeling, usually affecting the feet and ankles first.
      High incidence of falls and knock on effects in quality of life are common. This is a
      lifelong condition which, though not life limiting, does not have a cure. Research into the
      effect of balance rehabilitation in people with CMT has been limited to traditional
      exercises, which do not address the complex nature of balance impairments in this condition.
      Multi-sensory rehabilitation has proved beneficial in improving balance in people with
      sensory neuropathy. Research shows that strengthening trunk muscles can improve balance in
      older people. Trunk and muscles close to it are largely unaffected in people with CMT,
      therefore these muscles could be strengthened in these patients. This study proposes to
      assess the feasibility of multi-sensory balance training, strength training with a focus on
      the trunk and muscles close to the trunk, and falls management education. This comprehensive
      approach is reflective of a clinical physiotherapy programme. Though a life-long condition,
      many people with CMT lead full lives. A home based programme is proposed to so that patients
      can fit it into their lives without having to travel for treatment. Therapists will use
      self-management principles within treatment. Measurements will be taken prior to and
      following treatment including physical measures, questionnaires and interviews. The
      physiotherapy interventions will be taught home and data collection will be at the National
      Hospital for Neurology and Neurosurgery, University College London Hospitals (UCLH).
A recent, unpublished focus group study of people with CMT found that they reported more
      falls than healthy people. They reported problems walking on uneven surfaces, difficulty
      getting off the floor and a necessity to consciously think about every step to avoid falling
      while walking (GM Ramdharry et al., 2015). A retrospective survey of people with CMT found
      that 89% of the 94 respondents reported falls to the ground. Half of them reported falling at
      least once a month with 5% falling every day (Ramdharry et al., 2011). We have just completed
      an exploratory study of factors predicting falls risk. Preliminary analysis of prospective
      falls data for 32 people over 6 months showed that they fell a median of 4 times (range 0 -
      54 falls) and functional balance performance may be predictive (Ramdharry et al., 2015). A
      study of people with CMT1a found that sensory impairment increased visual dependence for a
      static balance task (van der Linden et al., 2010). There has only been one small study of
      balance training in people with CMT, comparing a novel rehabilitation device with more
      traditional exercises (Matjacić and Zupan, 2006). Both interventions showed improvement in
      functional balance scores. Studies of proximal strength training in CMT have shown
      improvements in walking parameters (Chetlin et al., 2004; Lindeman et al., 1995), but the
      effect on balance has not been explored. Because of the mixed sensori-motor presentation of
      people with CMT, a combined approach of multi-sensory balance training and proximal
      strengthening will be delivered. A home-based model has been proposed as CMT is a life-long
      condition that needs to be managed by the individual outside of the medical or therapy
      environment.

      STUDY DESIGN & JUSTIFICATION A single blinded randomised controlled design has been chosen in
      this feasibility study. The intention is to see if there is an effect of the intervention to
      later be explored in a larger randomized controlled trial. A blinded assessor will measure
      balance performance prior to randomisation and following the 12 weeks of either intervention
      or control. They will also undertake qualitative interviews prior to randomization and
      following final measurement session. Interviews will inform the intervention and its
      acceptability. All participants will receive a falls assessment and falls education.
      Following randomisation, participants will either receive the 12-week intervention or control
      period. The intervention will include a holistic programme of physiotherapy including
      strength training of muscle groups unaffected by the condition and multi-sensory exercises to
      target balance. The program will be delivered by a physiotherapist trained in delivering
      treatment under the principles of self-management. Exercises will be carried out by the
      patients in their own homes and monitored by the research physiotherapist, progressing as
      appropriate. Those randomized to the control arm will receive monitoring telephone calls
      throughout this 12-week period.

      RECRUITMENT Patients will be recruited from outpatient neurology clinics at Queen Square
      which specialise in the diagnosis and management of CMT. Patients who fit the inclusion
      criteria will be approached and the trial will be described to them. Written information will
      be provided and arrangement made for a way to make contact once they have decided about
      whether they wish to proceed with screening. All patients who agree to proceed will go
      through a screening which will take place over the telephone. Those who pass screening will
      be provided with falls diary postcards or arrangement for falls diary emails, which they will
      be asked to monitor and report for one month. A sample will be invited for a qualitative
      interview. Arrangement will be made for them to attend a baseline measurement session, falls
      assessment, and falls education following the month-long falls monitoring.

      Measures will include:

      Patient reported questionnaires of balance confidence, mood, walking ability and physical
      functioning 10m walk test / 6 minute walk test Berg Balance Scale Bruininks Oseretsky Test
      (BOT) BESTest Functional balance tests using force plate and movement analysis equipment
      Strength testing of the lower limbs and hands Charcot Marie Tooth Examination Score (CMTES) A
      block randomisation will occur following the baseline measurement and falls education session
      with allocation either being to a control arm or an intervention arm. This will be done by
      the PI or research physiotherapist who will remain un-blinded. Contact with the blinded
      assessor will cease until the final measurement session 12 weeks later.

      INTERVENTION:

      If randomised to the control arm of the study, participants will be advised that the research
      physiotherapist will contact them monthly to monitor any falls or issues. For those
      randomised to the intervention arm, a home visit will be arranged with the research
      physiotherapist as soon as possible. During this session, the research physiotherapist will
      provide the participant with exercises to strengthen the muscles of the trunk and proximal
      muscles using body weight and graded ankle weights. Strength training will be performed 4
      times per week. They will also give a selection of exercises targeting balance to challenge
      stability and sensory feedback. Participants will be asked to perform balance exercises
      daily. A risk assessment will be undertaken with guidance on how to ensure safety when doing
      the exercises. An exercise diary will be provided for the participants to monitor exercise
      frequency.

      Arrangements will be made for weekly telephone calls with the research physiotherapist to
      monitor progress and a provisional date set for the first monthly home monitoring visit.
      Participants in the intervention arm will be contacted weekly for 12 weeks on the study. The
      research physiotherapist will visit them at home to monitor and progress exercises once a
      month during this time.

      QUALITATIVE RESEARCH At the consent meeting all patients will be invited to take part in
      interviews conducted after the consent meeting and following completion of the final
      measurements. They will be made aware that participation in the interviews is supplementary
      to the main study and they are free to decline. Purposive sampling will be used to ensure a
      sample of maximum diversity of age, gender, and symptom severity. Potential qualitative
      interview participants will be given written details of the qualitative study and asked to
      give their consent to be interviewed if they are willing to take part. The interview will be
      audio recorded and consist of a dialogue between the interviewer (the researcher) and the
      participant. A topic guide will be used during the interviews, but the participant will be
      invited to raise issues of importance to them. Data analysis will be iterative, in that it
      will be continually analysed throughout the data collection process and used to inform
      following interviews.

      PROCEDURES TO DEAL WITH RESEARCHER EFFECTS AND BIAS Assessments will be carried out by a
      blinded assessor to standardise treatment during tests. Falls assessment and falls education
      will be provided at the baseline measurement session by the blinded assessor, prior to
      participant randomisation. In this way participants will be given the same treatment. The
      blinded assessor will perform final measurements. The participant will be reminded prior to
      the start the final session to not mention what they may or may not have been doing in the 12
      weeks prior to maintain blinding throughout the session
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Investigator)
measure: Balance performance
time frame: 12 weeks
description: Balance performance will be measured using laboratory measures of postural stability during static and dynamic tasks. Centre of pressure excursion and velocity will be the main variables
measure: Recruitment rate
time frame: 1 year
description: For this feasibility study, recruitment rate data will be gathered
measure: Falls monitoring
time frame: 20 weeks
description: Falls monitoring will be done one month before, during the 12 week invention/control period and one month afterwards using postcards or a web based app, depending on participant preference.
measure: Bruininks Oseretsky Test (BOT)
time frame: 12 weeks
description: Clinician rated measure of functional balance performance.
measure: Berg Balance test
time frame: 12 weeks
description: Clinician rated measure of functional balance performance.
measure: BESTest
time frame: 12 weeks
description: Clinician rated measure of functional balance performance.
measure: 10 minute timed walk
time frame: 12 weeks
description: Walking speed test
measure: Quantitative lower limb muscle strength testing
time frame: 12 weeks
description: Hand-held myometry protocol performed by rater for the major lower limb muscle groups.
measure: CMTES: Charcot Marie Tooth Examination Score
time frame: 12 weeks
description: Clinician rated disease severity scale
measure: Falls Self Efficacy Scale
time frame: 12 weeks
description: Patient reported outcome measure of balance confidence. Questionnaire.
measure: Walk-12
time frame: 12 weeks
description: Patient reported outcome measure of walking function. Questionnaire.
measure: IPAQ: International Physical Activity Questionnaire
time frame: 12 weeks
description: Patient reported outcome measure of physical activity. Questionnaire.
measure: SF36: Short Form 36
time frame: 12 weeks
description: Patient reported outcome measure of health related quality of life. Questionnaire.
measure: Hospital Anxiety and Depression Score
time frame: 12 weeks
description: Patient reported outcome measure of depression and anxiety symptoms. Questionnaire.
arm group label: Falls management plus exercise training
arm group type: Experimental
description: Falls management and education session. Home proximal lower limb strength training and multi-sensory balance training.
arm group label: Falls management only
arm group type: Active Comparator
description: Falls management and education session only.
intervention type: Behavioral
intervention name: Falls management plus exercise training
description: Participants will undergo a session of falls management and education followed by 12 weeks of strength and balance training. Strength training will be performed 4 times per week. Resistance training of the proximal muscles will be prescribed progressing to loads of 60% of 1 repetition maximum, 8-12 repetitions. Weaker muscles will be trained using 2 sets of 8-12 repetitions against gravity. They will also give a selection of exercises targeting balance to challenge stability and sensory feedback using equipment such as foam cushions, though will be individual based on participants' limitations and abilities. Participants will be asked to perform balance exercises daily.
arm group label: Falls management plus exercise training
intervention type: Behavioral
intervention name: Falls management only
description: Participants will undergo a session of falls management and education.
arm group label: Falls management only
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Gita M Ramdharry, PhD
role: Principal Investigator
affiliation: University College London Hosptials NHS Trust
facility: 
country: United Kingdom
citation: Ramdharry, G., M. Dudziec, D. Tropman, E. Dewar, A. Wallace, M. Laura, R. Grant, and M. Reilly. 2015. 'Exploring the Causes of Falls and Balance Impairments in People with Charcot-Marie Tooth Disease'. Physiotherapy 101 (May): e1255. doi:10.1016/j.physio.2015.03.1159.
citation: Ramdharry GM, Pollard A, Anderson C, Laura M, Murphy SM, Dudziec M, Dewar EL, Hutton E, Grant R, Reilly MM. A pilot study of proximal strength training in Charcot-Marie-Tooth disease. J Peripher Nerv Syst. 2014 Dec;19(4):328-32. doi: 10.1111/jns.12100.
PMID: 25582960
citation: van der Linden MH, van der Linden SC, Hendricks HT, van Engelen BG, Geurts AC. Postural instability in Charcot-Marie-Tooth type 1A patients is strongly associated with reduced somatosensation. Gait Posture. 2010 Apr;31(4):483-8. doi: 10.1016/j.gaitpost.2010.02.005. Epub 2010 Mar 11.
PMID: 20226674
citation: Matjacic Z, Zupan A. Effects of dynamic balance training during standing and stepping in patients with hereditary sensory motor neuropathy. Disabil Rehabil. 2006 Dec 15;28(23):1455-9. doi: 10.1080/09638280600646169.
PMID: 17166808
citation: Chetlin RD, Gutmann L, Tarnopolsky M, Ullrich IH, Yeater RA. Resistance training effectiveness in patients with Charcot-Marie-Tooth disease: recommendations for exercise prescription. Arch Phys Med Rehabil. 2004 Aug;85(8):1217-23. doi: 10.1016/j.apmr.2003.12.025.
PMID: 15295743
citation: Lindeman E, Leffers P, Spaans F, Drukker J, Reulen J, Kerckhoffs M, Koke A. Strength training in patients with myotonic dystrophy and hereditary motor and sensory neuropathy: a randomized clinical trial. Arch Phys Med Rehabil. 1995 Jul;76(7):612-20. doi: 10.1016/s0003-9993(95)80629-6.
PMID: 7605179
responsible party type: Principal Investigator
investigator affiliation: University College London Hospitals
investigator full name: Gita Ramdharry
investigator title: Principle Investigator
mesh term: Tooth Diseases
mesh term: Charcot-Marie-Tooth Disease
mesh term: Nerve Compression Syndromes
mesh term: Hereditary Sensory and Motor Neuropathy
sharing ipd: No