<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/NCT03809845</url>
  </required_header>
  <id_info>
    <org_study_id>KCH17-105</org_study_id>
    <nct_id>NCT03809845</nct_id>
  </id_info>
  <brief_title>Serial Fasciculation Measurements in Motor Neurone Disease</brief_title>
  <official_title>Sequential High-density Surface Electromyography (HDSEMG) Recordings in Motor Neurone Disease: Fasciculations as a Biomarker of Motor Neurone Health</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>King's College Hospital NHS Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>King's College Hospital NHS Trust</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with motor neurone disease (MND) typically experience relentless motor decline and&#xD;
      die within three years of symptom onset from respiratory muscle weakness. There are currently&#xD;
      no effective therapies and the discovery of novel therapies is hampered by the lack of a&#xD;
      sensitive disease biomarker. Consequently, there is a huge drive to discover novel&#xD;
      biomarkers, which can reliably track disease progression over time. These can then be&#xD;
      incorporated into clinical drug trials to expedite effective drug discovery.&#xD;
&#xD;
      Muscle fasciculations represent the hyperexcitability of diseased motor neurons and are&#xD;
      almost universally present from the early stages of MND. The investigators predict that the&#xD;
      site, frequency and shape of fasciculations might provide a sensitive measure of disease&#xD;
      progression in an individual.&#xD;
&#xD;
      In order to calibrate this technique, the investigators will conduct a 12-month longitudinal&#xD;
      study, recruiting 24 patients from the King's College Hospital Motor Nerve Clinic, comprising&#xD;
      a mixture of patients with MND and those with benign fasciculation syndrome. Patients in this&#xD;
      latter group have fasciculations but do not develop weakness and have normal lifespans. They&#xD;
      are therefore an optimal control group. At each visit, the investigators will take resting&#xD;
      HDSEMG recordings from all four limbs and perform standard clinical measures of disease&#xD;
      progression. The investigators will also monitor the decline in motor unit number using a&#xD;
      newly validated neurophysiological technique, called Motor Unit Number Index (MUNIX).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 6, 2017</start_date>
  <completion_date type="Actual">March 1, 2019</completion_date>
  <primary_completion_date type="Actual">March 1, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>20 Motor Neuron Disease (MND) patients and 5 Benign Fasciculation Syndrome (BFS) patients undergoing same assessments at 2-monthly intervals for one year</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in fasciculation frequency over time</measure>
    <time_frame>12 months</time_frame>
    <description>To characterise the frequency of fasciculations in patients with motor neurone disease and to determine whether these parameters correlate with the trajectory of disease progression over a 12-month period.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in fasciculation morphology over time</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Functional Rating Scale (FRS) over time</measure>
    <time_frame>12 months</time_frame>
    <description>Maximum score of 48; lower scores indicate worse disability</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in motor unit number index measurements over time</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in MRC power sum score over time</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in slow vital capacity over time</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Motor Neuron Disease</condition>
  <condition>Benign Fasciculation-Cramp Syndrome</condition>
  <arm_group>
    <arm_group_label>Motor neuron disease</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Benign fasciculation syndrome</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>High-density surface electromyography</intervention_name>
    <description>High-density surface electromyography</description>
    <arm_group_label>Benign fasciculation syndrome</arm_group_label>
    <arm_group_label>Motor neuron disease</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria for MND patients:&#xD;
&#xD;
        (i) Aged between 40 and 80 years of age inclusive, at the time of signing the informed&#xD;
        consent.&#xD;
&#xD;
        (ii) Diagnosed with MND by a neurologist with expertise in MND.(20) For subjects with&#xD;
        bulbar onset there must be objective limb involvement of at least one limb.&#xD;
&#xD;
        (iii) Diagnosed with MND within 24 months of symptom onset. (iv) Subjects must be&#xD;
        ambulatory (i.e. must not be confined to a wheelchair). (v) Male and female subjects (vi)&#xD;
        Capable of giving signed informed consent (vii) Capable and willing to comply with the&#xD;
        requirements of the protocol (either by themselves or with assistance).&#xD;
&#xD;
        Inclusion criteria for Benign Fasciculation Syndrome (BFS) patients:&#xD;
&#xD;
        (i) Aged between 18 and 80 years of age inclusive, at the time of signing the informed&#xD;
        consent.&#xD;
&#xD;
        (ii) Diagnosed with BFS by a neurologist with expertise in motor nerve disorders.&#xD;
&#xD;
        (iii) Male and female subjects (vi) Capable of giving signed informed consent (vii) Capable&#xD;
        and willing to comply with the requirements of the protocol (either by themselves or with&#xD;
        assistance).&#xD;
&#xD;
        Exclusion criteria for MND patients:&#xD;
&#xD;
        (i) Neurological (other than the subject's MND) or non-neurological co-morbidities (e.g.&#xD;
        joint disease, respiratory disease) which limit mobility.&#xD;
&#xD;
        (ii) Clinically significant cognitive impairment in the opinion of the investigator or&#xD;
        lacking capacity in accordance with the Mental Capacity Act (2005).&#xD;
&#xD;
        (iii) Regionally restricted forms of MND, or other atypical variants:&#xD;
&#xD;
          -  Isolated corticobulbar pattern of MND with normal ambulation&#xD;
&#xD;
          -  Primary lateral sclerosis&#xD;
&#xD;
          -  Signs of chronic partial denervation restricted to a single limb&#xD;
&#xD;
          -  MND or parkinsonism dementia complex (iv) Subjects requiring mechanical ventilation&#xD;
             (non-invasive ventilation for sleep apnoea is allowed).&#xD;
&#xD;
             (v) Historical or current evidence of clinically significant uncontrolled disease&#xD;
             which, in the opinion of the chief investigator, would put the safety of the subject&#xD;
             at risk through participation or impact the study assessments or endpoints.&#xD;
&#xD;
        (vi) Presence of an active implantable cardiac medical device (e.g., pacemaker or&#xD;
        implantable cardioverter-defibrillator) or at a high risk for needing external&#xD;
        defibrillation.&#xD;
&#xD;
        (vii) History of skin hypersensitivity to adhesives. (viii) Current participation in a&#xD;
        clinical trial which in the opinion of the chief investigator might impact the objectives&#xD;
        of this study.&#xD;
&#xD;
        Exclusion criteria for Benign Fasciculation Syndrome patients:&#xD;
&#xD;
        (i) Significant diagnostic uncertainty, whereby motor neurone disease remains a possible&#xD;
        differential diagnosis.&#xD;
&#xD;
        (ii) Historical or current evidence of clinically significant uncontrolled disease which,&#xD;
        in the opinion of the chief investigator, would put the safety of the subject at risk&#xD;
        through participation or impact the study assessments or endpoints.&#xD;
&#xD;
        (iii) Presence of an active implantable cardiac medical device (e.g., pacemaker or&#xD;
        implantable cardioverter-defibrillator) or at a high risk for needing external&#xD;
        defibrillation.&#xD;
&#xD;
        (iv) History of skin hypersensitivity to adhesives. (v) Current participation in a clinical&#xD;
        trial which in the opinion of the chief investigator might impact the objectives of this&#xD;
        study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>King's College Hospital NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>March 13, 2018</study_first_submitted>
  <study_first_submitted_qc>January 17, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <last_update_submitted>August 20, 2019</last_update_submitted>
  <last_update_submitted_qc>August 20, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Motor Neuron Disease</mesh_term>
    <mesh_term>Amyotrophic Lateral Sclerosis</mesh_term>
    <mesh_term>Fasciculation</mesh_term>
    <mesh_term>Neuromuscular Diseases</mesh_term>
  </condition_browse>
  <!-- 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/NCT03809845
org study id: KCH17-105
nct id: NCT03809845
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Patients with motor neurone disease (MND) typically experience relentless motor decline and
      die within three years of symptom onset from respiratory muscle weakness. There are currently
      no effective therapies and the discovery of novel therapies is hampered by the lack of a
      sensitive disease biomarker. Consequently, there is a huge drive to discover novel
      biomarkers, which can reliably track disease progression over time. These can then be
      incorporated into clinical drug trials to expedite effective drug discovery.

      Muscle fasciculations represent the hyperexcitability of diseased motor neurons and are
      almost universally present from the early stages of MND. The investigators predict that the
      site, frequency and shape of fasciculations might provide a sensitive measure of disease
      progression in an individual.

      In order to calibrate this technique, the investigators will conduct a 12-month longitudinal
      study, recruiting 24 patients from the King's College Hospital Motor Nerve Clinic, comprising
      a mixture of patients with MND and those with benign fasciculation syndrome. Patients in this
      latter group have fasciculations but do not develop weakness and have normal lifespans. They
      are therefore an optimal control group. At each visit, the investigators will take resting
      HDSEMG recordings from all four limbs and perform standard clinical measures of disease
      progression. The investigators will also monitor the decline in motor unit number using a
      newly validated neurophysiological technique, called Motor Unit Number Index (MUNIX).
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: 20 Motor Neuron Disease (MND) patients and 5 Benign Fasciculation Syndrome (BFS) patients undergoing same assessments at 2-monthly intervals for one year
primary purpose: Other
masking: None (Open Label)
measure: Change in fasciculation frequency over time
time frame: 12 months
description: To characterise the frequency of fasciculations in patients with motor neurone disease and to determine whether these parameters correlate with the trajectory of disease progression over a 12-month period.
measure: Change in fasciculation morphology over time
time frame: 12 months
measure: Change in Functional Rating Scale (FRS) over time
time frame: 12 months
description: Maximum score of 48; lower scores indicate worse disability
measure: Change in motor unit number index measurements over time
time frame: 12 months
measure: Change in MRC power sum score over time
time frame: 12 months
measure: Change in slow vital capacity over time
time frame: 12 months
arm group label: Motor neuron disease
arm group type: Active Comparator
arm group label: Benign fasciculation syndrome
arm group type: Active Comparator
intervention type: Device
intervention name: High-density surface electromyography
description: High-density surface electromyography
arm group label: Benign fasciculation syndrome
arm group label: Motor neuron disease
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Motor Neuron Disease
mesh term: Amyotrophic Lateral Sclerosis
mesh term: Fasciculation
mesh term: Neuromuscular Diseases