<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/NCT04467255</url>
  </required_header>
  <id_info>
    <org_study_id>2185</org_study_id>
    <nct_id>NCT04467255</nct_id>
  </id_info>
  <brief_title>Surface Electromyography Study of Fatigue in Diabetic Neuropathy</brief_title>
  <official_title>Muscular Fatigue Evaluation in Patients With Diabetic Neuropathy by Means of Multichannel Surface Electromyography After a Rehabilitative Training: Aerobic Versus Endurance Training.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Istituti Clinici Scientifici Maugeri SpA</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Istituti Clinici Scientifici Maugeri SpA</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>
      Fatigue in diabetic neuropathy compromises patients' physical activity and poses questions on&#xD;
      how to plan correct rehabilitation training. Conclusive interpretation of muscular mechanisms&#xD;
      of fatigue in diabetic neuropathy has not yet been achieved. Among the various instrumental&#xD;
      evaluations for fatigue, multichannel surface electromyography (sEMG) is a recognized tool&#xD;
      that permits the study of myoelectric manifestations of fatigue. Aim of the study is to&#xD;
      assess if differences in myoelectric manifestations of fatigue between patients affected by&#xD;
      diabetic neuropathy exist after an aerobic or endurance training.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The instrumental session consisted of the registration of sEMG signals during electrically&#xD;
      stimulated and voluntary contractions according to a consolidated standardized protocol. The&#xD;
      investigated muscle is the Anterior Tibial.&#xD;
&#xD;
      Each subjects sat comfortably on a chair with his/her ankle flexed at 90° degree and knee&#xD;
      extended; the leg was fixed at 90 degrees, in the isometric brace fixed on a plane (MISO1,&#xD;
      LISiN Bioengineering Centre, Turin Polytechnic, Italy Torque was measured with a modular&#xD;
      brace incorporating two independent torque transducers (model TR11, CCT Transducers, Torino,&#xD;
      Italy).&#xD;
&#xD;
      The signal from the two torque meters were amplified, summed and displayed by means of a&#xD;
      visual feedback system, which provided the subject with information regarding the torque&#xD;
      level produced. Torque signal were stored to be analysed later.&#xD;
&#xD;
      The sEMG signal of the right Anterior Tibial was investigated with a flexible adhesive linear&#xD;
      array of 16 electrodes (silver bars 10 mm long, 1 mm diameter, 10 mm apart) in single&#xD;
      differential (SD) configuration. The optimal position and orientation of the array was&#xD;
      determined at moderate contraction levels by visual inspection of the signal. It provided&#xD;
      clear motor unit action potentials with similar propagation in the two directions from the&#xD;
      neuromuscular junction to the tendons.&#xD;
&#xD;
      The reference electrode was positioned on the patient's leg. The skin was cleaned by slightly&#xD;
      abrading it with abrasive gel before positioning the array.&#xD;
&#xD;
      Since sEMG variables are affected by muscle temperature, the skin temperature was monitored&#xD;
      with an electronic thermometer throughout the whole examination and was kept between 31.5 C°&#xD;
      and 32.5 C° 30.&#xD;
&#xD;
      The protocol consisted in three evaluations: one stimulated contraction and two voluntary&#xD;
      contractions, according to a standardized protocol.&#xD;
&#xD;
      The stimulated contraction was executed through a button stimulation electrode (size: 10 mm)&#xD;
      positioned on the motor point using a monopolar configuration, a frequency of 25 Hz for a&#xD;
      duration of 30 seconds and a supramaximal stimulation. The motor point was selected as the&#xD;
      position of the stimulated electrode on the skin where the M-wave showed the maximum&#xD;
      amplitude for a specified stimulation intensity; the supramaximal stimulation level was&#xD;
      defined as the current intensity above which there was no significant increase of the&#xD;
      amplitude of the M-wave or the maximum level tolerated by the subjects.&#xD;
&#xD;
      A rest period of 10 minutes after stimulation was observed in order to avoid cumulative&#xD;
      fatigue phenomenon.&#xD;
&#xD;
      The subject then performed two test-contractions by dorsiflexion of the foot against the&#xD;
      resistance given by the braces, in order to get acquainted with the procedure and to verify&#xD;
      the correct posture and position of the array.&#xD;
&#xD;
      The subject was subsequently asked to produce three maximal voluntary contractions (MVC)&#xD;
      lasting 3 seconds each with a rest period of 2 minutes in-between. The reference MVC,&#xD;
      expressed in Nm, was established as the maximum of the three measurements. The last MVC&#xD;
      measurement was followed by a 10-minute rest period.&#xD;
&#xD;
      The subject then produced two voluntary contractions each lasting 30 seconds: one contraction&#xD;
      at 30% MVC and one at 60% MVC with a 5-minute rest in between. A visual biofeedback was used&#xD;
      to help the subject maintaining the requested contraction level; furthermore, the subjects&#xD;
      were verbally encouraged to obtain the best outcome during their performance.&#xD;
&#xD;
      The EMG signals were filtered with a 10-500 Hz bandwidth filter, amplified (EMG 16-16 channel&#xD;
      amplifiers LISiN Bioengineering Centre Turin Polytechnic). They were sampled at 2048 Hz&#xD;
      during voluntary contractions and 1024 Hz during electrically elicited contractions. Signals&#xD;
      were digitised by a 16 bit A/D converter (DAQCARD-6024E National Instruments, Austin, Texas,&#xD;
      USA) and stored on the disk of a personal computer.&#xD;
&#xD;
      Signal processing was performed using MATLAB. EMG variables of interest were: mean normalized&#xD;
      frequency (MNF), average rectified value (ARV) and muscle fibre conduction velocity (CV).&#xD;
      Spectral (i.e. MNF), amplitude (i.e. ARV) and CV variables were computed with numerical&#xD;
      algorithms described in previous papers.&#xD;
&#xD;
      CV was estimated from the consecutive double differential signals showing the best signal&#xD;
      propagation; MNF and ARV were estimated from the single differential channel in the middle of&#xD;
      the channels used for CV estimation. Epoch length for EMG variable estimation was 0.5 seconds&#xD;
      without overlapping.&#xD;
&#xD;
      A linear regression was used to fit all the scatter graphs of the EMG variables with time.&#xD;
      The rate of change was defined as the slope of the regression line. The normalized rate of&#xD;
      change for all variables was defined as the ratio between the slope and the intercept&#xD;
      (initial value of sEMG variables) expressed as percentage. Physiological myoelectric&#xD;
      manifestations of muscle fatigue consist in reduction of MNF and CV and increase of ARV.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 3, 2018</start_date>
  <completion_date type="Anticipated">July 2023</completion_date>
  <primary_completion_date type="Anticipated">April 2023</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>
    <intervention_model_description>Participants are assigned to two groups in parallel for the duration of the study</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Six-minute walk test</measure>
    <time_frame>4 weeks</time_frame>
    <description>The score of the test is the distance a patient walks in 6 minutes measured in meters.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Modified Borg Scale</measure>
    <time_frame>4 weeks</time_frame>
    <description>Is is commonly used to assess fatigue during a training expressed with Dyspnea. This is a0 to 10 rated scale. High score corresponds to worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional Independence Measure</measure>
    <time_frame>4 weeks</time_frame>
    <description>The functional Independence measure is an 18-item measurement tool that explores an individual's physical, psychological and social function. The tool is used to assess a patient's level of disability. Range total score 18-126. High score corresponds to better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Surface multichannel electromyographic variables.</measure>
    <time_frame>4 weeks</time_frame>
    <description>In research setting muscle electric properties were analyzed during contractions employing multichannel surface electromyograpy. Among the variables describing muscle activity, we examine conduction velocity. The conduction velocity of the muscle was estimated from the difference in arrival time of the motor unit potential at electrodes separeted by 15 mm. The motor unit conduction velocity for anterior tibial, analyzed in this study, ranged from 2.6 to 5.3 m/s (mean 3.7 m/s) (Arendt-Nielsen SA and L. J Physiol (1987), 391, pp 561-571).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Neuropathy</condition>
  <condition>Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>group a</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>aerobic training</description>
  </arm_group>
  <arm_group>
    <arm_group_label>group b</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>endurance training</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Rehabilitative training</intervention_name>
    <description>4 weeks aerobic treadmill training compared to endurance training with elastic thera band</description>
    <arm_group_label>group a</arm_group_label>
    <arm_group_label>group b</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Michigan Neuropathy Screening instrument higher or equal to 7&#xD;
&#xD;
          -  Stable clinical conditions&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Other neurological conditions or diseases&#xD;
&#xD;
          -  Skin lesions&#xD;
&#xD;
          -  Recent lower limb fractures or lower limb surgical intervention&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Cira Fundarò, MD</last_name>
    <phone>0385247268</phone>
    <email>cira.fundaro@icsmaugeri.it</email>
  </overall_contact>
  <location>
    <facility>
      <name>Ics Maugeri</name>
      <address>
        <city>Montescano</city>
        <state>Pavia</state>
        <zip>27040</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Cira Fundarò, MD</last_name>
      <phone>0385247268</phone>
      <phone_ext>0385247268</phone_ext>
      <email>cira.fundaro@icsmaugeri.it</email>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Callaghan BC, Cheng HT, Stables CL, Smith AL, Feldman EL. Diabetic neuropathy: clinical manifestations and current treatments. Lancet Neurol. 2012 Jun;11(6):521-34. doi: 10.1016/S1474-4422(12)70065-0. Epub 2012 May 16.</citation>
    <PMID>22608666</PMID>
  </reference>
  <reference>
    <citation>Chipkin SR, Klugh SA, Chasan-Taber L. Exercise and diabetes. Cardiol Clin. 2001 Aug;19(3):489-505. doi: 10.1016/s0733-8651(05)70231-9.</citation>
    <PMID>11570119</PMID>
  </reference>
  <reference>
    <citation>Fritschi C, Quinn L. Fatigue in patients with diabetes: a review. J Psychosom Res. 2010 Jul;69(1):33-41. doi: 10.1016/j.jpsychores.2010.01.021. Epub 2010 Mar 23.</citation>
    <PMID>20630261</PMID>
  </reference>
  <reference>
    <citation>Watanabe K, Gazzoni M, Holobar A, Miyamoto T, Fukuda K, Merletti R, Moritani T. Motor unit firing pattern of vastus lateralis muscle in type 2 diabetes mellitus patients. Muscle Nerve. 2013 Nov;48(5):806-13. doi: 10.1002/mus.23828. Epub 2013 Aug 30.</citation>
    <PMID>23447092</PMID>
  </reference>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>June 23, 2020</study_first_submitted>
  <study_first_submitted_qc>July 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 10, 2020</study_first_posted>
  <last_update_submitted>November 17, 2022</last_update_submitted>
  <last_update_submitted_qc>November 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 18, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>sEMG, diabetic neuropathy, fatigue, training</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>Fatigue</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/NCT04467255
org study id: 2185
nct id: NCT04467255
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Fatigue in diabetic neuropathy compromises patients' physical activity and poses questions on
      how to plan correct rehabilitation training. Conclusive interpretation of muscular mechanisms
      of fatigue in diabetic neuropathy has not yet been achieved. Among the various instrumental
      evaluations for fatigue, multichannel surface electromyography (sEMG) is a recognized tool
      that permits the study of myoelectric manifestations of fatigue. Aim of the study is to
      assess if differences in myoelectric manifestations of fatigue between patients affected by
      diabetic neuropathy exist after an aerobic or endurance training.
The instrumental session consisted of the registration of sEMG signals during electrically
      stimulated and voluntary contractions according to a consolidated standardized protocol. The
      investigated muscle is the Anterior Tibial.

      Each subjects sat comfortably on a chair with his/her ankle flexed at 90° degree and knee
      extended; the leg was fixed at 90 degrees, in the isometric brace fixed on a plane (MISO1,
      LISiN Bioengineering Centre, Turin Polytechnic, Italy Torque was measured with a modular
      brace incorporating two independent torque transducers (model TR11, CCT Transducers, Torino,
      Italy).

      The signal from the two torque meters were amplified, summed and displayed by means of a
      visual feedback system, which provided the subject with information regarding the torque
      level produced. Torque signal were stored to be analysed later.

      The sEMG signal of the right Anterior Tibial was investigated with a flexible adhesive linear
      array of 16 electrodes (silver bars 10 mm long, 1 mm diameter, 10 mm apart) in single
      differential (SD) configuration. The optimal position and orientation of the array was
      determined at moderate contraction levels by visual inspection of the signal. It provided
      clear motor unit action potentials with similar propagation in the two directions from the
      neuromuscular junction to the tendons.

      The reference electrode was positioned on the patient's leg. The skin was cleaned by slightly
      abrading it with abrasive gel before positioning the array.

      Since sEMG variables are affected by muscle temperature, the skin temperature was monitored
      with an electronic thermometer throughout the whole examination and was kept between 31.5 C°
      and 32.5 C° 30.

      The protocol consisted in three evaluations: one stimulated contraction and two voluntary
      contractions, according to a standardized protocol.

      The stimulated contraction was executed through a button stimulation electrode (size: 10 mm)
      positioned on the motor point using a monopolar configuration, a frequency of 25 Hz for a
      duration of 30 seconds and a supramaximal stimulation. The motor point was selected as the
      position of the stimulated electrode on the skin where the M-wave showed the maximum
      amplitude for a specified stimulation intensity; the supramaximal stimulation level was
      defined as the current intensity above which there was no significant increase of the
      amplitude of the M-wave or the maximum level tolerated by the subjects.

      A rest period of 10 minutes after stimulation was observed in order to avoid cumulative
      fatigue phenomenon.

      The subject then performed two test-contractions by dorsiflexion of the foot against the
      resistance given by the braces, in order to get acquainted with the procedure and to verify
      the correct posture and position of the array.

      The subject was subsequently asked to produce three maximal voluntary contractions (MVC)
      lasting 3 seconds each with a rest period of 2 minutes in-between. The reference MVC,
      expressed in Nm, was established as the maximum of the three measurements. The last MVC
      measurement was followed by a 10-minute rest period.

      The subject then produced two voluntary contractions each lasting 30 seconds: one contraction
      at 30% MVC and one at 60% MVC with a 5-minute rest in between. A visual biofeedback was used
      to help the subject maintaining the requested contraction level; furthermore, the subjects
      were verbally encouraged to obtain the best outcome during their performance.

      The EMG signals were filtered with a 10-500 Hz bandwidth filter, amplified (EMG 16-16 channel
      amplifiers LISiN Bioengineering Centre Turin Polytechnic). They were sampled at 2048 Hz
      during voluntary contractions and 1024 Hz during electrically elicited contractions. Signals
      were digitised by a 16 bit A/D converter (DAQCARD-6024E National Instruments, Austin, Texas,
      USA) and stored on the disk of a personal computer.

      Signal processing was performed using MATLAB. EMG variables of interest were: mean normalized
      frequency (MNF), average rectified value (ARV) and muscle fibre conduction velocity (CV).
      Spectral (i.e. MNF), amplitude (i.e. ARV) and CV variables were computed with numerical
      algorithms described in previous papers.

      CV was estimated from the consecutive double differential signals showing the best signal
      propagation; MNF and ARV were estimated from the single differential channel in the middle of
      the channels used for CV estimation. Epoch length for EMG variable estimation was 0.5 seconds
      without overlapping.

      A linear regression was used to fit all the scatter graphs of the EMG variables with time.
      The rate of change was defined as the slope of the regression line. The normalized rate of
      change for all variables was defined as the ratio between the slope and the intercept
      (initial value of sEMG variables) expressed as percentage. Physiological myoelectric
      manifestations of muscle fatigue consist in reduction of MNF and CV and increase of ARV.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants are assigned to two groups in parallel for the duration of the study
primary purpose: Basic Science
masking: None (Open Label)
measure: Six-minute walk test
time frame: 4 weeks
description: The score of the test is the distance a patient walks in 6 minutes measured in meters.
measure: Modified Borg Scale
time frame: 4 weeks
description: Is is commonly used to assess fatigue during a training expressed with Dyspnea. This is a0 to 10 rated scale. High score corresponds to worse outcome.
measure: Functional Independence Measure
time frame: 4 weeks
description: The functional Independence measure is an 18-item measurement tool that explores an individual's physical, psychological and social function. The tool is used to assess a patient's level of disability. Range total score 18-126. High score corresponds to better outcome.
measure: Surface multichannel electromyographic variables.
time frame: 4 weeks
description: In research setting muscle electric properties were analyzed during contractions employing multichannel surface electromyograpy. Among the variables describing muscle activity, we examine conduction velocity. The conduction velocity of the muscle was estimated from the difference in arrival time of the motor unit potential at electrodes separeted by 15 mm. The motor unit conduction velocity for anterior tibial, analyzed in this study, ranged from 2.6 to 5.3 m/s (mean 3.7 m/s) (Arendt-Nielsen SA and L. J Physiol (1987), 391, pp 561-571).
arm group label: group a
arm group type: Active Comparator
description: aerobic training
arm group label: group b
arm group type: Active Comparator
description: endurance training
intervention type: Other
intervention name: Rehabilitative training
description: 4 weeks aerobic treadmill training compared to endurance training with elastic thera band
arm group label: group a
arm group label: group b
criteria: 
gender: All
minimum age: 65 Years
maximum age: 85 Years
healthy volunteers: No
last name: Cira Fundarò, MD
phone: 0385247268
email: cira.fundaro@icsmaugeri.it
facility: 
status: Recruiting
contact: 
country: Italy
citation: Callaghan BC, Cheng HT, Stables CL, Smith AL, Feldman EL. Diabetic neuropathy: clinical manifestations and current treatments. Lancet Neurol. 2012 Jun;11(6):521-34. doi: 10.1016/S1474-4422(12)70065-0. Epub 2012 May 16.
PMID: 22608666
citation: Chipkin SR, Klugh SA, Chasan-Taber L. Exercise and diabetes. Cardiol Clin. 2001 Aug;19(3):489-505. doi: 10.1016/s0733-8651(05)70231-9.
PMID: 11570119
citation: Fritschi C, Quinn L. Fatigue in patients with diabetes: a review. J Psychosom Res. 2010 Jul;69(1):33-41. doi: 10.1016/j.jpsychores.2010.01.021. Epub 2010 Mar 23.
PMID: 20630261
citation: Watanabe K, Gazzoni M, Holobar A, Miyamoto T, Fukuda K, Merletti R, Moritani T. Motor unit firing pattern of vastus lateralis muscle in type 2 diabetes mellitus patients. Muscle Nerve. 2013 Nov;48(5):806-13. doi: 10.1002/mus.23828. Epub 2013 Aug 30.
PMID: 23447092
responsible party type: Sponsor
mesh term: Peripheral Nervous System Diseases
mesh term: Diabetic Neuropathies
mesh term: Fatigue
sharing ipd: No