<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/NCT03256747</url>
  </required_header>
  <id_info>
    <org_study_id>68437417.0.0000.5327</org_study_id>
    <nct_id>NCT03256747</nct_id>
  </id_info>
  <brief_title>Effects of Neuromuscular Electrical Stimulation on Glucose Variability in Patients With Type 2 Diabetes</brief_title>
  <official_title>Effects of Neuromuscular Electrical Stimulation on Glucose Levels and Glucose Variability in Patients With Type 2 Diabetes: a Randomized Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital de Clinicas de Porto Alegre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital de Clinicas de Porto Alegre</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>
      In patients with type 2 diabetes mellitus (T2DM) chronic hyperglycemia is the main cause of&#xD;
      complications, promoting several micro and macrovascular damages. In order to understand&#xD;
      other mechanisms that could have an impact on the development of these diabetic&#xD;
      complications, the assessment of glycemic variability have been widely used. Glucose control&#xD;
      can be achieved with multiple interventions, including exercise training. Some individuals,&#xD;
      however, especially those with autonomic neuropathy, can have exercise intolerance. In this&#xD;
      context, physical therapy proposes neuromuscular electrical stimulation (NMES) as a&#xD;
      therapeutic that has been applied in research and clinical practice as an alternative to the&#xD;
      training of patients who cannot perform conventional exercise. In patients with T2DM, NMES&#xD;
      was shown to improve glycemic control and insulin sensitivity, but quality of these trials is&#xD;
      poor. In addition, the effects of NMES on glycemic variability of T2DM patients have not yet&#xD;
      been reported. The aim of this study is to evaluate the effects of NMES on glucose levels and&#xD;
      glucose variability in patients with T2DM.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with T2DM will be recruited from outpatient clinic of the Hospital de Clinicas de&#xD;
      Porto Alegre. Patients will be randomized to NMES session, with maximal intensity tolerance&#xD;
      by to induce visible contractions or to NMES-placebo, with minimal intensity to provide a&#xD;
      sensory stimulus, but insufficient to elicit a tetanic muscular contraction. Subjects will&#xD;
      attend to research facility four times. On the first visit clinical, physical examination and&#xD;
      autonomic evaluation (Ewing test) will be performed and a blood sample will be collected. On&#xD;
      the second visit CGMS will be placed for glycemic variability evaluation. On the third visit&#xD;
      NMES or NMES-placebo will be performed in a randomized way. On the fourth visit the CGMS will&#xD;
      be removed. Blood pressure and heart rate will be evaluated during the protocol each 5&#xD;
      minutes and oxygenation tissue will be evaluated before, during and immediately after the&#xD;
      protocol, through NIRS.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 15, 2017</start_date>
  <completion_date type="Actual">May 30, 2020</completion_date>
  <primary_completion_date type="Actual">March 30, 2020</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 (Outcomes Assessor)</masking>
    <masking_description>GCMS record will be coded and analyzed by a blinded investigator</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Glucose levels</measure>
    <time_frame>48 hours</time_frame>
    <description>Glucose levels will be assessed through continuous glucose monitoring (CGMS)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Glucose variability</measure>
    <time_frame>48 hours</time_frame>
    <description>Glucose variability will be assessed by CGMS 24 hours before, during the protocol and 24 hours after protocol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>Each 5 minutes during intervention which will last 60 minutes.</time_frame>
    <description>Will be evaluated through non-invasive oscillometric device.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart Rate</measure>
    <time_frame>Each 5 minutes during intervention which will last 60 minutes.</time_frame>
    <description>Will be evaluated through non-invasive oscillometric device.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oxygenation tissue</measure>
    <time_frame>Before, during and immediately after the intervention which will last 60 minutes.</time_frame>
    <description>Will be evaluated through near infrared spectroscopy (NIRS).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Type2 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>NMES group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>NMES will be placed at the knee extensors, with maximal intensity tolerance evaluated by to induce visible contractions.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NMES-placebo group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>NMES-placebo will be placed at the knee extensors, with minimal intensity to provide a sensory stimulus, but insufficient to elicit a tetanic muscular contraction.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>NMES</intervention_name>
    <description>NMES will be placed at the knee extensors. Stimulation frequency will be 20 Hz. Pulse width will be 0.5 milliseconds and the contraction time will be 10 seconds (TON: 10s) with a 5-second rest interval (TOFF: 5s). Total time application will be 60 minutes. Intensity will be adjusted individually, taking into account the patient's ability to promote the full knee extension and comfort during contractions.</description>
    <arm_group_label>NMES group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>NMES-placebo</intervention_name>
    <description>NMES-placebo will be placed at the knee extensors. Stimulation frequency will be 20 Hz. Pulse width will be 0.5 milliseconds and the contraction time will be 10 seconds (TON: 10s) with a 5-second rest interval (TOFF: 5s). Total time of application will be 60 minutes. Intensity will be adjusted with minimal intensity, utilized to provide a sensory stimulus, but insufficient to elicit a tetanic muscular contraction.</description>
    <arm_group_label>NMES-placebo group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Type 2 diabetes;&#xD;
&#xD;
          -  HbA1c from 7,5 to 10%;&#xD;
&#xD;
          -  Fasting plasma glucose lower to 250 mg/dL&#xD;
&#xD;
          -  Drug therapy maintained for at least one month before inclusion in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Insulin use;&#xD;
&#xD;
          -  Pregnancy;&#xD;
&#xD;
          -  Documented arrhythmia;&#xD;
&#xD;
          -  Unstable angina;&#xD;
&#xD;
          -  Chronic renal failure (GFR lower than 15 ml/min);&#xD;
&#xD;
          -  Varicose vein problems;&#xD;
&#xD;
          -  Clinical musculoskeletal disease.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Beatriz D Schaan, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>HCPA</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Aline C P Macedo</name>
      <address>
        <city>Porto Alegre</city>
        <state>RS</state>
        <zip>90570040</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <reference>
    <citation>Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000 Aug 12;321(7258):405-12. doi: 10.1136/bmj.321.7258.405.</citation>
    <PMID>10938048</PMID>
  </reference>
  <reference>
    <citation>Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes. 2005 Jun;54(6):1615-25. doi: 10.2337/diabetes.54.6.1615. No abstract available.</citation>
    <PMID>15919781</PMID>
  </reference>
  <reference>
    <citation>Monnier L, Wojtusciszyn A, Colette C, Owens D. The contribution of glucose variability to asymptomatic hypoglycemia in persons with type 2 diabetes. Diabetes Technol Ther. 2011 Aug;13(8):813-8. doi: 10.1089/dia.2011.0049. Epub 2011 May 11.</citation>
    <PMID>21561372</PMID>
  </reference>
  <reference>
    <citation>Standards of Medical Care in Diabetes-2017: Summary of Revisions. Diabetes Care. 2017 Jan;40(Suppl 1):S4-S5. doi: 10.2337/dc17-S003. No abstract available.</citation>
    <PMID>27979887</PMID>
  </reference>
  <reference>
    <citation>Green S, Egana M, Baldi JC, Lamberts R, Regensteiner JG. Cardiovascular control during exercise in type 2 diabetes mellitus. J Diabetes Res. 2015;2015:654204. doi: 10.1155/2015/654204. Epub 2015 Mar 30.</citation>
    <PMID>25918732</PMID>
  </reference>
  <reference>
    <citation>Sbruzzi G, Ribeiro RA, Schaan BD, Signori LU, Silva AM, Irigoyen MC, Plentz RD. Functional electrical stimulation in the treatment of patients with chronic heart failure: a meta-analysis of randomized controlled trials. Eur J Cardiovasc Prev Rehabil. 2010 Jun;17(3):254-60. doi: 10.1097/HJR.0b013e328339b5a2.</citation>
    <PMID>20560163</PMID>
  </reference>
  <reference>
    <citation>Crowe L, Caulfield B. Aerobic neuromuscular electrical stimulation--an emerging technology to improve haemoglobin A1c in type 2 diabetes mellitus: results of a pilot study. BMJ Open. 2012 Jun 14;2(3):e000219. doi: 10.1136/bmjopen-2011-000219. Print 2012.</citation>
    <PMID>22700835</PMID>
  </reference>
  <reference>
    <citation>Joubert M, Metayer L, Prevost G, Morera J, Rod A, Cailleux A, Parienti JJ, Reznik Y. Neuromuscular electrostimulation and insulin sensitivity in patients with type 2 diabetes: the ELECTRODIAB pilot study. Acta Diabetol. 2015 Apr;52(2):285-91. doi: 10.1007/s00592-014-0636-5. Epub 2014 Aug 9.</citation>
    <PMID>25107502</PMID>
  </reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>August 7, 2017</study_first_submitted>
  <study_first_submitted_qc>August 17, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 22, 2017</study_first_posted>
  <last_update_submitted>July 31, 2020</last_update_submitted>
  <last_update_submitted_qc>July 31, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Diabetes Mellitus</keyword>
  <keyword>Diabetes Mellitus, Type 2</keyword>
  <keyword>Glucose Metabolism Disorders</keyword>
  <keyword>Metabolic Diseases</keyword>
  <keyword>Endocrine System Diseases</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03256747
org study id: 68437417.0.0000.5327
nct id: NCT03256747
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
In patients with type 2 diabetes mellitus (T2DM) chronic hyperglycemia is the main cause of
      complications, promoting several micro and macrovascular damages. In order to understand
      other mechanisms that could have an impact on the development of these diabetic
      complications, the assessment of glycemic variability have been widely used. Glucose control
      can be achieved with multiple interventions, including exercise training. Some individuals,
      however, especially those with autonomic neuropathy, can have exercise intolerance. In this
      context, physical therapy proposes neuromuscular electrical stimulation (NMES) as a
      therapeutic that has been applied in research and clinical practice as an alternative to the
      training of patients who cannot perform conventional exercise. In patients with T2DM, NMES
      was shown to improve glycemic control and insulin sensitivity, but quality of these trials is
      poor. In addition, the effects of NMES on glycemic variability of T2DM patients have not yet
      been reported. The aim of this study is to evaluate the effects of NMES on glucose levels and
      glucose variability in patients with T2DM.
Patients with T2DM will be recruited from outpatient clinic of the Hospital de Clinicas de
      Porto Alegre. Patients will be randomized to NMES session, with maximal intensity tolerance
      by to induce visible contractions or to NMES-placebo, with minimal intensity to provide a
      sensory stimulus, but insufficient to elicit a tetanic muscular contraction. Subjects will
      attend to research facility four times. On the first visit clinical, physical examination and
      autonomic evaluation (Ewing test) will be performed and a blood sample will be collected. On
      the second visit CGMS will be placed for glycemic variability evaluation. On the third visit
      NMES or NMES-placebo will be performed in a randomized way. On the fourth visit the CGMS will
      be removed. Blood pressure and heart rate will be evaluated during the protocol each 5
      minutes and oxygenation tissue will be evaluated before, during and immediately after the
      protocol, through NIRS.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: GCMS record will be coded and analyzed by a blinded investigator
measure: Glucose levels
time frame: 48 hours
description: Glucose levels will be assessed through continuous glucose monitoring (CGMS)
measure: Glucose variability
time frame: 48 hours
description: Glucose variability will be assessed by CGMS 24 hours before, during the protocol and 24 hours after protocol.
measure: Blood pressure
time frame: Each 5 minutes during intervention which will last 60 minutes.
description: Will be evaluated through non-invasive oscillometric device.
measure: Heart Rate
time frame: Each 5 minutes during intervention which will last 60 minutes.
description: Will be evaluated through non-invasive oscillometric device.
measure: Oxygenation tissue
time frame: Before, during and immediately after the intervention which will last 60 minutes.
description: Will be evaluated through near infrared spectroscopy (NIRS).
arm group label: NMES group
arm group type: Experimental
description: NMES will be placed at the knee extensors, with maximal intensity tolerance evaluated by to induce visible contractions.
arm group label: NMES-placebo group
arm group type: Placebo Comparator
description: NMES-placebo will be placed at the knee extensors, with minimal intensity to provide a sensory stimulus, but insufficient to elicit a tetanic muscular contraction.
intervention type: Device
intervention name: NMES
description: NMES will be placed at the knee extensors. Stimulation frequency will be 20 Hz. Pulse width will be 0.5 milliseconds and the contraction time will be 10 seconds (TON: 10s) with a 5-second rest interval (TOFF: 5s). Total time application will be 60 minutes. Intensity will be adjusted individually, taking into account the patient's ability to promote the full knee extension and comfort during contractions.
arm group label: NMES group
intervention type: Device
intervention name: NMES-placebo
description: NMES-placebo will be placed at the knee extensors. Stimulation frequency will be 20 Hz. Pulse width will be 0.5 milliseconds and the contraction time will be 10 seconds (TON: 10s) with a 5-second rest interval (TOFF: 5s). Total time of application will be 60 minutes. Intensity will be adjusted with minimal intensity, utilized to provide a sensory stimulus, but insufficient to elicit a tetanic muscular contraction.
arm group label: NMES-placebo group
criteria: 
gender: All
minimum age: 30 Years
maximum age: N/A
healthy volunteers: No
last name: Beatriz D Schaan, PhD
role: Principal Investigator
affiliation: HCPA
facility: 
country: Brazil
citation: Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000 Aug 12;321(7258):405-12. doi: 10.1136/bmj.321.7258.405.
PMID: 10938048
citation: Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes. 2005 Jun;54(6):1615-25. doi: 10.2337/diabetes.54.6.1615. No abstract available.
PMID: 15919781
citation: Monnier L, Wojtusciszyn A, Colette C, Owens D. The contribution of glucose variability to asymptomatic hypoglycemia in persons with type 2 diabetes. Diabetes Technol Ther. 2011 Aug;13(8):813-8. doi: 10.1089/dia.2011.0049. Epub 2011 May 11.
PMID: 21561372
citation: Standards of Medical Care in Diabetes-2017: Summary of Revisions. Diabetes Care. 2017 Jan;40(Suppl 1):S4-S5. doi: 10.2337/dc17-S003. No abstract available.
PMID: 27979887
citation: Green S, Egana M, Baldi JC, Lamberts R, Regensteiner JG. Cardiovascular control during exercise in type 2 diabetes mellitus. J Diabetes Res. 2015;2015:654204. doi: 10.1155/2015/654204. Epub 2015 Mar 30.
PMID: 25918732
citation: Sbruzzi G, Ribeiro RA, Schaan BD, Signori LU, Silva AM, Irigoyen MC, Plentz RD. Functional electrical stimulation in the treatment of patients with chronic heart failure: a meta-analysis of randomized controlled trials. Eur J Cardiovasc Prev Rehabil. 2010 Jun;17(3):254-60. doi: 10.1097/HJR.0b013e328339b5a2.
PMID: 20560163
citation: Crowe L, Caulfield B. Aerobic neuromuscular electrical stimulation--an emerging technology to improve haemoglobin A1c in type 2 diabetes mellitus: results of a pilot study. BMJ Open. 2012 Jun 14;2(3):e000219. doi: 10.1136/bmjopen-2011-000219. Print 2012.
PMID: 22700835
citation: Joubert M, Metayer L, Prevost G, Morera J, Rod A, Cailleux A, Parienti JJ, Reznik Y. Neuromuscular electrostimulation and insulin sensitivity in patients with type 2 diabetes: the ELECTRODIAB pilot study. Acta Diabetol. 2015 Apr;52(2):285-91. doi: 10.1007/s00592-014-0636-5. Epub 2014 Aug 9.
PMID: 25107502
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
sharing ipd: Undecided