<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/NCT03767478</url>
  </required_header>
  <id_info>
    <org_study_id>18HH4610</org_study_id>
    <secondary_id>IRAS ID</secondary_id>
    <secondary_id>NRES REC ID</secondary_id>
    <nct_id>NCT03767478</nct_id>
  </id_info>
  <brief_title>Neuromuscular Electrical Stimulation For The Treatment of Diabetic Neuropathy</brief_title>
  <acronym>NMES-DN</acronym>
  <official_title>Neuromuscular Electrical Stimulation For The Treatment Of Diabetic Neuropathy: A Multicentre, Double-blind, Pilot, Randomised, Sham-controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Imperial College London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Actegy Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Imperial College London</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>
      Diabetic neuropathy (DN) is the most common complication of diabetes, affecting almost 50% of&#xD;
      people with diabetes over the course of their lives. Symptoms vary from numbness to burning,&#xD;
      aching and hypersensitivity in the lower limbs, indicative of sensory nerve loss. Motor&#xD;
      neurons can also be affected, leading to muscle weakness and mobility issues, thus preventing&#xD;
      patients from engaging in daily routines. Further sequelae include foot ulceration and&#xD;
      Charcot neuroarthropathy, which are risk factors for lower limb amputation and mortality. In&#xD;
      the United Kingdom, the annual costs of DN alone exceed £300 million, with further&#xD;
      complications expected to cost an additional £1 billion. Currently, management strategies for&#xD;
      DN focus on prevention and pain management. Neuromuscular electrical stimulation (NMES) is a&#xD;
      novel nonpharmacological intervention for people with DN. NMES is the application of&#xD;
      electrical impulses which are of sufficiency intensity to improve artificial contraction of&#xD;
      the muscle tissue and may help with DN by improving nerve conductivity through direct&#xD;
      stimulation of the nerves.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">August 1, 2023</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2024</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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Primary outcome measure: sural nerve conductivity measured using a nerve conduction study at 6 months. This includes conduction velocity (m/s), calculated using distance and latency (ms), and sensory nerve action potential (SNAP) amplitude (μV).</measure>
    <time_frame>Month 6</time_frame>
    <description>Multi-component, single outcome. Nerve conduction parameters include sural nerve conduction velocity (m/s) and SNAP amplitude (µV).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Feasibility outcome measure: recruitment rate measured using screening and randomisation logs.</measure>
    <time_frame>Pre-screening / Identification, Recruitment and Consent, Baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Feasibility outcome measure: participant retention rate measured using randomisation and withdrawal logs.</measure>
    <time_frame>Recruitment and Consent, Baseline, Month 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Feasibility outcome measure: adherence to treatment measured using Revitive App and a patient diary.</measure>
    <time_frame>Month 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety outcome measure: Adverse Events (AEs) collected and reported via AE form.</measure>
    <time_frame>Baseline, Week 2, Month 6, Month 9 (and any communication in between)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety outcome measure: Adverse Device Effects (ADEs) collected and reported via AE form.</measure>
    <time_frame>Baseline, Week 2, Month 6, Month 9 (and any communication in between)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety outcome measure: Serious Adverse Events (SAEs) collected and reported via SAE form.</measure>
    <time_frame>Baseline, Week 2, Month 6, Month 9 (and any communication in between)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety outcome measure: Serious Adverse Device Effects (SADEs) collected and reported via SAE form.</measure>
    <time_frame>Baseline, Week 2, Month 6, Month 9 (and any communication in between)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary outcome measure: superficial peroneal nerve conductivity measured using a nerve conduction study.</measure>
    <time_frame>Month 6, Month 9</time_frame>
    <description>Nerve conduction parameters include conduction velocity (m/s), calculated using distance and latency (ms), and SNAP amplitude (μV).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary outcome measure: common peroneal nerve conductivity measured using a nerve conduction study.</measure>
    <time_frame>Month 6, Month 9</time_frame>
    <description>Nerve conduction parameters include conduction velocity (m/s), calculated using distance and distal latency (ms), Compound Muscle Action Potential (CMAP) amplitude (mV) and minimum F wave latency (ms).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary outcome measure: tibial nerve conductivity measured using a nerve conduction study.</measure>
    <time_frame>Month 6, Month 9</time_frame>
    <description>Nerve conduction parameters include conduction velocity (m/s), calculated using distance and distal latency (ms), Compound Muscle Action Potential (CMAP) amplitude (mV) and minimum F wave latency (ms).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary outcome measure: somatosensory nerve fibre function measured using Quantitative Sensory Testing (QST).</measure>
    <time_frame>Month 6, Month 9</time_frame>
    <description>Somatosensory nerve fibre function will be assessed using the German Research Network on Neuropathic Pain (DFNS) QST protocol. The battery of tests includes measures of cold and warm detection thresholds, paradoxical heat sensations, cold and heat pain thresholds, mechanical detection threshold, mechanical pain threshold, mechanical pain sensitivity, dynamic mechanical allodynia, temporal pain summation, vibration detection threshold and pressure pain threshold.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary outcome measure: mobility and balance measured using validated Berg Balance Scale (BBS).</measure>
    <time_frame>Month 6, Month 9</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary outcome measure: quality of life measured using validated EQ-5D-5L questionnaire.</measure>
    <time_frame>Month 6, Month 9</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary outcome measure: illness perceptions measured using validated Brief Illness Perception Questionnaire (Brief IPQ).</measure>
    <time_frame>Month 6, Month 9</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary outcome measure: neuropathy signs and symptoms measured using validated screening questionnaire, Michigan Neuropathy Screening Instrument (MNSI).</measure>
    <time_frame>Month 6, Month 9</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary outcome measure: neuropathy symptoms measured using validated Self-administered Neuropathy Total Symptom Score (NTSS-6-SA).</measure>
    <time_frame>Month 6, Month 9</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary outcome measure: protected sensation measured using monofilament test.</measure>
    <time_frame>Month 6, Month 9</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary outcome measure: neuropathic pain measured using Neuropathic Pain Symptom Inventory (NPSI).</measure>
    <time_frame>Month 6, Month 9</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary outcome measure: daily pain measured using 11-point Numerical Rating Scale (NRS) collected via text message.</measure>
    <time_frame>Daily for treatment phase (6 months)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary outcome measure: daily sleep interference measured using Daily Sleep Interference Scale (DSIS) (30) collected via text message.</measure>
    <time_frame>Daily for treatment phase (6 months)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary outcome measure: peripheral arterial perfusion measured using Ankle Brachial Pressure Index (ABPI).</measure>
    <time_frame>Baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary outcome measure: device sensation measured using device sensory threshold and suprathreshold.</measure>
    <time_frame>Month 6, Month 9</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary outcome measure: device experience measured using device experience questionnaire.</measure>
    <time_frame>Month 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary outcome measure: device credibility and expectancy measured using modified credibility and expectancy questionnaire.</measure>
    <time_frame>Baseline</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Diabetic Peripheral Neuropathy</condition>
  <condition>Diabetic Neuropathies</condition>
  <condition>Diabetic Polyneuropathy</condition>
  <condition>Diabetic Complication</condition>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Best Medical Therapy + Sham Revitive Medic Coach (Sham Neuromuscular Electrical Stimulation Device) for 6 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intervention group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Best Medical Therapy + Revitive Medic Coach (Neuromuscular Electrical Stimulation Device) for 6 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Revitive Medic Coach (Actegy Ltd)</intervention_name>
    <description>Use the device for two 30-minute sessions per day, a minimum of five hours per week for 6 months at suprathreshold (2 x motor threshold).</description>
    <arm_group_label>Intervention group</arm_group_label>
    <other_name>Footplate Neuromuscular Electrical Stimulation Device</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham Revitive Medic Coach (Actegy Ltd)</intervention_name>
    <description>Use the device for two 30-minute sessions per day, a minimum of five hours per week for 6 months at suprathreshold (2 x motor threshold).</description>
    <arm_group_label>Control group</arm_group_label>
    <other_name>Sham Footplate Neuromuscular Electrical Stimulation Device</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        INCLUSION CRITERIA&#xD;
&#xD;
          -  Aged ≥18 (no upper limit)&#xD;
&#xD;
          -  Diagnosis of type 1 or type 2 diabetes based on World Health Organisation (WHO)&#xD;
             definition&#xD;
&#xD;
          -  Diagnosis of diabetic neuropathy based on:&#xD;
&#xD;
               -  symptoms of diabetic neuropathy&#xD;
&#xD;
               -  validated screening questionnaire Michigan Neuropathy Screening Instrument score&#xD;
                  of ≥4&#xD;
&#xD;
               -  nerve conduction study of at least one lower limb must have a sural SNAP&#xD;
                  amplitude of &lt;6 μV or absent&#xD;
&#xD;
          -  Access to internet at home to use the Revitive App (study smartphones will be&#xD;
             provided)&#xD;
&#xD;
          -  Personal mobile phone to receive text messages&#xD;
&#xD;
        EXCLUSION CRITERIA&#xD;
&#xD;
          -  Lacks capacity to provide informed consent&#xD;
&#xD;
          -  Pregnant&#xD;
&#xD;
          -  Implanted electronic, cardiac or defibrillator device&#xD;
&#xD;
          -  Other cause of peripheral neuropathy (e.g. excessive drinking, low levels of vitamin&#xD;
             B12 or other vitamins, syphilis, HIV, underactive thyroid gland)&#xD;
&#xD;
          -  Current foot ulceration&#xD;
&#xD;
          -  Severe vascular disease requiring invasive intervention&#xD;
&#xD;
          -  Being treated for, or have the symptoms of, an existing deep vein thrombosis (DVT)&#xD;
&#xD;
          -  Used a neuromuscular electrical stimulation (NMES) device within 1 year of&#xD;
             randomisation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alun H Davies, MA DM DSC FRCS FEBVS</last_name>
    <role>Study Chair</role>
    <affiliation>Imperial College London</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Tristan R A Lane, MBBS BSc FRCS PhD</last_name>
    <phone>02033117317</phone>
    <email>tristan.lane@imperial.ac.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Sasha K Smith, BSc</last_name>
    <email>sasha.smith@imperial.ac.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Imperial College London</name>
      <address>
        <city>London</city>
        <zip>W6 8RF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <contact>
      <last_name>Tristan R Lane, PhD FRCS</last_name>
      <email>tristan.lane@imperial.ac.uk</email>
    </contact>
    <contact_backup>
      <last_name>Sasha Smith, BSc</last_name>
      <email>sasha.smith@imperial.ac.uk</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>November 27, 2018</study_first_submitted>
  <study_first_submitted_qc>December 5, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 6, 2018</study_first_posted>
  <last_update_submitted>July 13, 2023</last_update_submitted>
  <last_update_submitted_qc>July 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Neuromuscular electrical stimulation</keyword>
  <keyword>Nerve conduction</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Peripheral Nervous System Diseases</mesh_term>
    <mesh_term>Diabetic Neuropathies</mesh_term>
    <mesh_term>Polyneuropathies</mesh_term>
    <mesh_term>Diabetes Complications</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Available on request.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
  </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/NCT03767478
org study id: 18HH4610
secondary id: IRAS ID
secondary id: NRES REC ID
nct id: NCT03767478
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Diabetic neuropathy (DN) is the most common complication of diabetes, affecting almost 50% of
      people with diabetes over the course of their lives. Symptoms vary from numbness to burning,
      aching and hypersensitivity in the lower limbs, indicative of sensory nerve loss. Motor
      neurons can also be affected, leading to muscle weakness and mobility issues, thus preventing
      patients from engaging in daily routines. Further sequelae include foot ulceration and
      Charcot neuroarthropathy, which are risk factors for lower limb amputation and mortality. In
      the United Kingdom, the annual costs of DN alone exceed £300 million, with further
      complications expected to cost an additional £1 billion. Currently, management strategies for
      DN focus on prevention and pain management. Neuromuscular electrical stimulation (NMES) is a
      novel nonpharmacological intervention for people with DN. NMES is the application of
      electrical impulses which are of sufficiency intensity to improve artificial contraction of
      the muscle tissue and may help with DN by improving nerve conductivity through direct
      stimulation of the nerves.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Primary outcome measure: sural nerve conductivity measured using a nerve conduction study at 6 months. This includes conduction velocity (m/s), calculated using distance and latency (ms), and sensory nerve action potential (SNAP) amplitude (μV).
time frame: Month 6
description: Multi-component, single outcome. Nerve conduction parameters include sural nerve conduction velocity (m/s) and SNAP amplitude (µV).
measure: Feasibility outcome measure: recruitment rate measured using screening and randomisation logs.
time frame: Pre-screening / Identification, Recruitment and Consent, Baseline
measure: Feasibility outcome measure: participant retention rate measured using randomisation and withdrawal logs.
time frame: Recruitment and Consent, Baseline, Month 6
measure: Feasibility outcome measure: adherence to treatment measured using Revitive App and a patient diary.
time frame: Month 6
measure: Safety outcome measure: Adverse Events (AEs) collected and reported via AE form.
time frame: Baseline, Week 2, Month 6, Month 9 (and any communication in between)
measure: Safety outcome measure: Adverse Device Effects (ADEs) collected and reported via AE form.
time frame: Baseline, Week 2, Month 6, Month 9 (and any communication in between)
measure: Safety outcome measure: Serious Adverse Events (SAEs) collected and reported via SAE form.
time frame: Baseline, Week 2, Month 6, Month 9 (and any communication in between)
measure: Safety outcome measure: Serious Adverse Device Effects (SADEs) collected and reported via SAE form.
time frame: Baseline, Week 2, Month 6, Month 9 (and any communication in between)
measure: Secondary outcome measure: superficial peroneal nerve conductivity measured using a nerve conduction study.
time frame: Month 6, Month 9
description: Nerve conduction parameters include conduction velocity (m/s), calculated using distance and latency (ms), and SNAP amplitude (μV).
measure: Secondary outcome measure: common peroneal nerve conductivity measured using a nerve conduction study.
time frame: Month 6, Month 9
description: Nerve conduction parameters include conduction velocity (m/s), calculated using distance and distal latency (ms), Compound Muscle Action Potential (CMAP) amplitude (mV) and minimum F wave latency (ms).
measure: Secondary outcome measure: tibial nerve conductivity measured using a nerve conduction study.
time frame: Month 6, Month 9
description: Nerve conduction parameters include conduction velocity (m/s), calculated using distance and distal latency (ms), Compound Muscle Action Potential (CMAP) amplitude (mV) and minimum F wave latency (ms).
measure: Secondary outcome measure: somatosensory nerve fibre function measured using Quantitative Sensory Testing (QST).
time frame: Month 6, Month 9
description: Somatosensory nerve fibre function will be assessed using the German Research Network on Neuropathic Pain (DFNS) QST protocol. The battery of tests includes measures of cold and warm detection thresholds, paradoxical heat sensations, cold and heat pain thresholds, mechanical detection threshold, mechanical pain threshold, mechanical pain sensitivity, dynamic mechanical allodynia, temporal pain summation, vibration detection threshold and pressure pain threshold.
measure: Secondary outcome measure: mobility and balance measured using validated Berg Balance Scale (BBS).
time frame: Month 6, Month 9
measure: Secondary outcome measure: quality of life measured using validated EQ-5D-5L questionnaire.
time frame: Month 6, Month 9
measure: Secondary outcome measure: illness perceptions measured using validated Brief Illness Perception Questionnaire (Brief IPQ).
time frame: Month 6, Month 9
measure: Secondary outcome measure: neuropathy signs and symptoms measured using validated screening questionnaire, Michigan Neuropathy Screening Instrument (MNSI).
time frame: Month 6, Month 9
measure: Secondary outcome measure: neuropathy symptoms measured using validated Self-administered Neuropathy Total Symptom Score (NTSS-6-SA).
time frame: Month 6, Month 9
measure: Secondary outcome measure: protected sensation measured using monofilament test.
time frame: Month 6, Month 9
measure: Secondary outcome measure: neuropathic pain measured using Neuropathic Pain Symptom Inventory (NPSI).
time frame: Month 6, Month 9
measure: Secondary outcome measure: daily pain measured using 11-point Numerical Rating Scale (NRS) collected via text message.
time frame: Daily for treatment phase (6 months)
measure: Secondary outcome measure: daily sleep interference measured using Daily Sleep Interference Scale (DSIS) (30) collected via text message.
time frame: Daily for treatment phase (6 months)
measure: Secondary outcome measure: peripheral arterial perfusion measured using Ankle Brachial Pressure Index (ABPI).
time frame: Baseline
measure: Secondary outcome measure: device sensation measured using device sensory threshold and suprathreshold.
time frame: Month 6, Month 9
measure: Secondary outcome measure: device experience measured using device experience questionnaire.
time frame: Month 6
measure: Secondary outcome measure: device credibility and expectancy measured using modified credibility and expectancy questionnaire.
time frame: Baseline
arm group label: Control group
arm group type: Sham Comparator
description: Best Medical Therapy + Sham Revitive Medic Coach (Sham Neuromuscular Electrical Stimulation Device) for 6 months
arm group label: Intervention group
arm group type: Active Comparator
description: Best Medical Therapy + Revitive Medic Coach (Neuromuscular Electrical Stimulation Device) for 6 months
intervention type: Device
intervention name: Revitive Medic Coach (Actegy Ltd)
description: Use the device for two 30-minute sessions per day, a minimum of five hours per week for 6 months at suprathreshold (2 x motor threshold).
arm group label: Intervention group
other name: Footplate Neuromuscular Electrical Stimulation Device
intervention type: Device
intervention name: Sham Revitive Medic Coach (Actegy Ltd)
description: Use the device for two 30-minute sessions per day, a minimum of five hours per week for 6 months at suprathreshold (2 x motor threshold).
arm group label: Control group
other name: Sham Footplate Neuromuscular Electrical Stimulation Device
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Alun H Davies, MA DM DSC FRCS FEBVS
role: Study Chair
affiliation: Imperial College London
last name: Tristan R A Lane, MBBS BSc FRCS PhD
phone: 02033117317
email: tristan.lane@imperial.ac.uk
last name: Sasha K Smith, BSc
email: sasha.smith@imperial.ac.uk
facility: 
contact: 
contact backup: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Peripheral Nervous System Diseases
mesh term: Diabetic Neuropathies
mesh term: Polyneuropathies
mesh term: Diabetes Complications
sharing ipd: Yes
ipd description: Available on request.
ipd info type: Study Protocol