<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/NCT03258489</url>
  </required_header>
  <id_info>
    <org_study_id>UFSM</org_study_id>
    <nct_id>NCT03258489</nct_id>
  </id_info>
  <brief_title>Effects of TENS and IES on the Autonomous Balance of Normotens Volunteers and Hypertensive Patients</brief_title>
  <official_title>Effects of Transcutaneous Nervous Electric Stimulation (TENS) and Interferential Electrical Stimulation (IES) on the Autonomous Balance of Normotens Volunteers and Hypertensive Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universidade Federal de Santa Maria</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Universidade Federal de Santa Maria</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>
      Hypertension is considered a serious public health problem. The imbalance in autonomic&#xD;
      nervous system (ANS) activity is one of the main triggers in the development and maintenance&#xD;
      of hypertension. The non-pharmacological management of this disease is an important resource,&#xD;
      especially in refractory hypertensive patients or in hypertensive crises, where the&#xD;
      pharmacological treatment does not present an efficient response. It is known that&#xD;
      transcutaneous electrical nerve stimulation (TENS) is capable of modifying the autonomic&#xD;
      balance, however, the effects of Interferential electrical stimulation (IES) on this system&#xD;
      in normotensive and hypertensive volunteers are not yet known. These electrotherapeutic&#xD;
      resources may be a non-pharmacological tool supporting the management of hypertension. The&#xD;
      objective of this research is to study the effects of different TENS and IC parameters on&#xD;
      cardiovascular variables of normotensive volunteers and hypertensive patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Each volunteer will perform three assessments with a one-week interval. Each assessment will&#xD;
      include assessment of autonomic balance, blood pressure, and blood collection&#xD;
      (catecholamines). Interventions (placebo, low frequency TENS and IES) will be randomized.&#xD;
      Volunteers will be accommodated in the supine position. With properly sanitized skin (70%&#xD;
      alcohol) and self-adhesive electrodes (5x5 area) will be positioned in the cervical&#xD;
      paravertebral region. All participants will be submitted to a placebo TENS session, a low&#xD;
      frequency TENS session (TENS, 10 Hz/200μs) and an IES session (STEIN et al., 2012). The&#xD;
      sessions will take place in the morning in a 12-hour fast, lasting 30 minutes, in an&#xD;
      air-conditioned place (23ºC).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 20, 2018</start_date>
  <completion_date type="Actual">December 9, 2019</completion_date>
  <primary_completion_date type="Actual">December 9, 2019</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Systemic arterial pressure (mmHg)</measure>
    <time_frame>SBP will be evaluated 1 hours after the interventions</time_frame>
    <description>Systemic arterial pressure (SBP) will be evaluated by an Ambulatory Blood Pressure Monitor (ABPM) (NOBRE et al., 2011). Micromed and version 5.0.1.52 equipment will be used. Blood pressure monitoring using ABPM will be performed every 10 min throughout the experiment, which has an estimated time of two hours.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Blood collection - catecholamines (pg/mL)</measure>
    <time_frame>Blood collection (catecholamines) will be evaluated 1 hours after the interventions</time_frame>
    <description>Plasma levels of catecholamines (dopamine, epinephrine and norepinephrine) will be evaluated before and after HPLC (High Performance Liquid Chromatography) interventions. Blood with heparin will be homogenized and immediately transferred to a special tube containing 120 μL of EGTA/GSH (reduced glutathione) solution. After being centrifuged and the plasma transferred to a plastic tube, it is placed in a freezer (-80ºC).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart Rate Variability (n.u.)</measure>
    <time_frame>HRV will be evaluated 1 hours after the interventions</time_frame>
    <description>The autonomic balance evaluate by heart rate variability (HRV) and the heart rate signal will be purchased through a pulse frequency meter mark Polar model 810i (GAMELIN et al., 2006). The acquisition of ECG signal (sample rate-1 kHz) of the time series of RR will be purchased in continuous intervals (10 min). Data Will be transferred to a computer and RR intervals. They will be processed to calculate HRV parameter using the HRV analysis software KUBIOS. HRV will be analyzed in the time and frequency domain, using the area of greatest stability in RR intervals corresponding to 5 min of recordings (containing at least 256 consecutive beats) during controlled breathing. Volunteers Will remain in a supine position at rest for 10 min and afterwards, data will be collected with controlled breathing (12 breaths per minute; I/E:2/3) (STEIN et al., 2011). Values expressed in Total Power (ms2) and normalization unit (n.u.) (GAMELIN et al., 2006).</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Healthy Volunteers</condition>
  <condition>Hypertension, Essential</condition>
  <arm_group>
    <arm_group_label>Transcutaneous nervous electric stimulation (TENS)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Autonomic balance, blood pressure, and blood collection (catecholamines) will be evaluated before and after TENS. The autonomic balance will be evaluated by heart rate variability (HRV), systemic arterial pressure (SBP) will be evaluated by an Ambulatory Blood Pressure Monitor (ABPM) and catecholamines of kits.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Interferential electrical stimulation (IES)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Autonomic balance, blood pressure, and blood collection (catecholamines) will be evaluated before and after Interferential electrical stimulation (IES). The autonomic balance will be evaluated by heart rate variability (HRV), systemic arterial pressure (SBP) will be evaluated by an Ambulatory Blood Pressure Monitor (ABPM) and catecholamines of kits.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TENS and IES Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Autonomic balance, blood pressure, and blood collection (catecholamines) will be evaluated before and after of the TENS and IES placebo. The autonomic balance will be evaluated by heart rate variability (HRV), systemic arterial pressure (SBP) will be evaluated by an Ambulatory Blood Pressure Monitor (ABPM) and catecholamines of kits.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Transcutaneous nervous electric stimulation (TENS)</intervention_name>
    <description>TENS (Frequency 10 Hz or 100Hz /duration 200μs, Endophasys nms 0501® model, KLD Biosystems, Amparo, SP, Brazil) will be applied with intensity between 1 to 60 mA and the current will be adjusted every 5 minutes at the sensory threshold level muscle contraction or according to the tolerance to the stimulus informed by the volunteers. TENS will be applied in bilateral paravertebral region of C7 to T4 or long the brachial plexus and sciatic plexus.</description>
    <arm_group_label>Transcutaneous nervous electric stimulation (TENS)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Interferential electrical stimulation (IES)</intervention_name>
    <description>The IES (Endophasys nms 0501®, KLD Biosystems, Amparo, SP, Brazil) will be applied in continuous mode with biphasic pulses. Bipolar electrodes with slope of 1/5/1. The rest of the parameters will be set to 4000 Hz, AMF of 100 Hz and the AMF variation of 25 Hz. The effect of the current will be adjusted by the intensity, it should produce paresthesia stimuli, without pain and below the motor threshold. Adhesive electrodes (MultiStick®, Axelgaard Manufacturing CO, Ltd, Fallbrook, CA, USA) will be housed in the paravertebral region, between C7 (Channel 1) and T4 (Channel 2). (SANTOS et al., 2013)</description>
    <arm_group_label>Interferential electrical stimulation (IES)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>TENS and IES Placebo</intervention_name>
    <description>Same protocol without electrical output.</description>
    <arm_group_label>TENS and IES Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Both sexes;&#xD;
&#xD;
          -  Normal blood pressure (PAS &lt;130 mmHg; PAD &lt;85 mmHg) or Previous Hypertension&#xD;
             diagnosis, systolic blood pressure (SBP) &gt; 140 mm Hg and/or diastolic blood pressure&#xD;
             (DBP) &gt;90 mm Hg and clinical stability with no change in medications for at least 2&#xD;
             months preceding the study;&#xD;
&#xD;
          -  The subjects that joined the study will be alphabetized volunteers;&#xD;
&#xD;
          -  Age between 20 and 65 years old;&#xD;
&#xD;
          -  With no symptoms of skeletal muscle disorders;&#xD;
&#xD;
          -  No previous performing cardiovascular surgery;&#xD;
&#xD;
          -  No previous diagnose of rheumatic, neurological, oncological, immune or hematologic&#xD;
             diseases;&#xD;
&#xD;
          -  Without evidence of psychiatric diseases and/or cognitive déficit;&#xD;
&#xD;
          -  Non-Smoker;&#xD;
&#xD;
          -  Volunteers with a body mass index (BMI: kg/m2) greater than 35 will not be included in&#xD;
             the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  On the day of the assessments who have consumed of the alcoholic drink, caffeine and&#xD;
             citrus juice and who have performed intense physical activities 48 before the&#xD;
             examination&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Luis Ulisses Signori</name>
      <address>
        <city>Santa Maria</city>
        <state>Rio Grande Do Sul</state>
        <zip>5596200190</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <results_reference>
    <citation>Gamelin FX, Berthoin S, Bosquet L. Validity of the polar S810 heart rate monitor to measure R-R intervals at rest. Med Sci Sports Exerc. 2006 May;38(5):887-93. doi: 10.1249/01.mss.0000218135.79476.9c.</citation>
    <PMID>16672842</PMID>
  </results_reference>
  <results_reference>
    <citation>Santos FV, Chiappa GR, Vieira PJ, Umpierre D, Ribeiro JP, Cipriano G Jr. Interferential electrical stimulation improves peripheral vasodilatation in healthy individuals. Braz J Phys Ther. 2013 May-Jun;17(3):281-8. doi: 10.1590/s1413-35552012005000092.</citation>
    <PMID>23966145</PMID>
  </results_reference>
  <results_reference>
    <citation>Sociedade Brasileira de Cardiologia (SBC); Sociedade Brasileira de Hipertensao (SBH); Sociedade Brasileira de Nefrologia (SBN). [V Guidelines for ambulatory blood pressure monitoring (ABPM) and III Guidelines for home blood pressure monitoring (HBPM)]. Arq Bras Cardiol. 2011 Sep;97(3 Suppl 3):1-24. No abstract available. Portuguese.</citation>
    <PMID>22262107</PMID>
  </results_reference>
  <results_reference>
    <citation>Stein C, Dal Lago P, Ferreira JB, Casali KR, Plentz RD. Transcutaneous electrical nerve stimulation at different frequencies on heart rate variability in healthy subjects. Auton Neurosci. 2011 Dec 7;165(2):205-8. doi: 10.1016/j.autneu.2011.07.003. Epub 2011 Aug 9.</citation>
    <PMID>21827970</PMID>
  </results_reference>
  <results_reference>
    <citation>Stein C, Mea Plentz RD. The effect of transcutaneous electrical nerve stimulation on blood pressure. Blood Press. 2013 Jun;22(3):188-9. doi: 10.3109/08037051.2012.722271. Epub 2012 Sep 25. No abstract available.</citation>
    <PMID>23004921</PMID>
  </results_reference>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>July 26, 2017</study_first_submitted>
  <study_first_submitted_qc>August 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 23, 2017</study_first_posted>
  <last_update_submitted>December 9, 2019</last_update_submitted>
  <last_update_submitted_qc>December 9, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 11, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universidade Federal de Santa Maria</investigator_affiliation>
    <investigator_full_name>Luis Ulisses Signori</investigator_full_name>
    <investigator_title>Principal Investigador</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Essential Hypertension</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/NCT03258489
org study id: UFSM
nct id: NCT03258489
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Hypertension is considered a serious public health problem. The imbalance in autonomic
      nervous system (ANS) activity is one of the main triggers in the development and maintenance
      of hypertension. The non-pharmacological management of this disease is an important resource,
      especially in refractory hypertensive patients or in hypertensive crises, where the
      pharmacological treatment does not present an efficient response. It is known that
      transcutaneous electrical nerve stimulation (TENS) is capable of modifying the autonomic
      balance, however, the effects of Interferential electrical stimulation (IES) on this system
      in normotensive and hypertensive volunteers are not yet known. These electrotherapeutic
      resources may be a non-pharmacological tool supporting the management of hypertension. The
      objective of this research is to study the effects of different TENS and IC parameters on
      cardiovascular variables of normotensive volunteers and hypertensive patients.
Each volunteer will perform three assessments with a one-week interval. Each assessment will
      include assessment of autonomic balance, blood pressure, and blood collection
      (catecholamines). Interventions (placebo, low frequency TENS and IES) will be randomized.
      Volunteers will be accommodated in the supine position. With properly sanitized skin (70%
      alcohol) and self-adhesive electrodes (5x5 area) will be positioned in the cervical
      paravertebral region. All participants will be submitted to a placebo TENS session, a low
      frequency TENS session (TENS, 10 Hz/200μs) and an IES session (STEIN et al., 2012). The
      sessions will take place in the morning in a 12-hour fast, lasting 30 minutes, in an
      air-conditioned place (23ºC).
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Systemic arterial pressure (mmHg)
time frame: SBP will be evaluated 1 hours after the interventions
description: Systemic arterial pressure (SBP) will be evaluated by an Ambulatory Blood Pressure Monitor (ABPM) (NOBRE et al., 2011). Micromed and version 5.0.1.52 equipment will be used. Blood pressure monitoring using ABPM will be performed every 10 min throughout the experiment, which has an estimated time of two hours.
measure: Blood collection - catecholamines (pg/mL)
time frame: Blood collection (catecholamines) will be evaluated 1 hours after the interventions
description: Plasma levels of catecholamines (dopamine, epinephrine and norepinephrine) will be evaluated before and after HPLC (High Performance Liquid Chromatography) interventions. Blood with heparin will be homogenized and immediately transferred to a special tube containing 120 μL of EGTA/GSH (reduced glutathione) solution. After being centrifuged and the plasma transferred to a plastic tube, it is placed in a freezer (-80ºC).
measure: Heart Rate Variability (n.u.)
time frame: HRV will be evaluated 1 hours after the interventions
description: The autonomic balance evaluate by heart rate variability (HRV) and the heart rate signal will be purchased through a pulse frequency meter mark Polar model 810i (GAMELIN et al., 2006). The acquisition of ECG signal (sample rate-1 kHz) of the time series of RR will be purchased in continuous intervals (10 min). Data Will be transferred to a computer and RR intervals. They will be processed to calculate HRV parameter using the HRV analysis software KUBIOS. HRV will be analyzed in the time and frequency domain, using the area of greatest stability in RR intervals corresponding to 5 min of recordings (containing at least 256 consecutive beats) during controlled breathing. Volunteers Will remain in a supine position at rest for 10 min and afterwards, data will be collected with controlled breathing (12 breaths per minute; I/E:2/3) (STEIN et al., 2011). Values expressed in Total Power (ms2) and normalization unit (n.u.) (GAMELIN et al., 2006).
arm group label: Transcutaneous nervous electric stimulation (TENS)
arm group type: Active Comparator
description: Autonomic balance, blood pressure, and blood collection (catecholamines) will be evaluated before and after TENS. The autonomic balance will be evaluated by heart rate variability (HRV), systemic arterial pressure (SBP) will be evaluated by an Ambulatory Blood Pressure Monitor (ABPM) and catecholamines of kits.
arm group label: Interferential electrical stimulation (IES)
arm group type: Active Comparator
description: Autonomic balance, blood pressure, and blood collection (catecholamines) will be evaluated before and after Interferential electrical stimulation (IES). The autonomic balance will be evaluated by heart rate variability (HRV), systemic arterial pressure (SBP) will be evaluated by an Ambulatory Blood Pressure Monitor (ABPM) and catecholamines of kits.
arm group label: TENS and IES Placebo
arm group type: Placebo Comparator
description: Autonomic balance, blood pressure, and blood collection (catecholamines) will be evaluated before and after of the TENS and IES placebo. The autonomic balance will be evaluated by heart rate variability (HRV), systemic arterial pressure (SBP) will be evaluated by an Ambulatory Blood Pressure Monitor (ABPM) and catecholamines of kits.
intervention type: Device
intervention name: Transcutaneous nervous electric stimulation (TENS)
description: TENS (Frequency 10 Hz or 100Hz /duration 200μs, Endophasys nms 0501® model, KLD Biosystems, Amparo, SP, Brazil) will be applied with intensity between 1 to 60 mA and the current will be adjusted every 5 minutes at the sensory threshold level muscle contraction or according to the tolerance to the stimulus informed by the volunteers. TENS will be applied in bilateral paravertebral region of C7 to T4 or long the brachial plexus and sciatic plexus.
arm group label: Transcutaneous nervous electric stimulation (TENS)
intervention type: Device
intervention name: Interferential electrical stimulation (IES)
description: The IES (Endophasys nms 0501®, KLD Biosystems, Amparo, SP, Brazil) will be applied in continuous mode with biphasic pulses. Bipolar electrodes with slope of 1/5/1. The rest of the parameters will be set to 4000 Hz, AMF of 100 Hz and the AMF variation of 25 Hz. The effect of the current will be adjusted by the intensity, it should produce paresthesia stimuli, without pain and below the motor threshold. Adhesive electrodes (MultiStick®, Axelgaard Manufacturing CO, Ltd, Fallbrook, CA, USA) will be housed in the paravertebral region, between C7 (Channel 1) and T4 (Channel 2). (SANTOS et al., 2013)
arm group label: Interferential electrical stimulation (IES)
intervention type: Device
intervention name: TENS and IES Placebo
description: Same protocol without electrical output.
arm group label: TENS and IES Placebo
criteria: 
gender: All
minimum age: 20 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Brazil
citation: Gamelin FX, Berthoin S, Bosquet L. Validity of the polar S810 heart rate monitor to measure R-R intervals at rest. Med Sci Sports Exerc. 2006 May;38(5):887-93. doi: 10.1249/01.mss.0000218135.79476.9c.
PMID: 16672842
citation: Santos FV, Chiappa GR, Vieira PJ, Umpierre D, Ribeiro JP, Cipriano G Jr. Interferential electrical stimulation improves peripheral vasodilatation in healthy individuals. Braz J Phys Ther. 2013 May-Jun;17(3):281-8. doi: 10.1590/s1413-35552012005000092.
PMID: 23966145
citation: Sociedade Brasileira de Cardiologia (SBC); Sociedade Brasileira de Hipertensao (SBH); Sociedade Brasileira de Nefrologia (SBN). [V Guidelines for ambulatory blood pressure monitoring (ABPM) and III Guidelines for home blood pressure monitoring (HBPM)]. Arq Bras Cardiol. 2011 Sep;97(3 Suppl 3):1-24. No abstract available. Portuguese.
PMID: 22262107
citation: Stein C, Dal Lago P, Ferreira JB, Casali KR, Plentz RD. Transcutaneous electrical nerve stimulation at different frequencies on heart rate variability in healthy subjects. Auton Neurosci. 2011 Dec 7;165(2):205-8. doi: 10.1016/j.autneu.2011.07.003. Epub 2011 Aug 9.
PMID: 21827970
citation: Stein C, Mea Plentz RD. The effect of transcutaneous electrical nerve stimulation on blood pressure. Blood Press. 2013 Jun;22(3):188-9. doi: 10.3109/08037051.2012.722271. Epub 2012 Sep 25. No abstract available.
PMID: 23004921
responsible party type: Principal Investigator
investigator affiliation: Universidade Federal de Santa Maria
investigator full name: Luis Ulisses Signori
investigator title: Principal Investigador
mesh term: Essential Hypertension
sharing ipd: Undecided