<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/NCT03252184</url>
  </required_header>
  <id_info>
    <org_study_id>PBMLLLT</org_study_id>
    <nct_id>NCT03252184</nct_id>
  </id_info>
  <brief_title>Effects of Photobiomodulation on Endothelial Function in Healthy Subjects</brief_title>
  <official_title>Effects of Photobiomodulation on Endothelial Function, Blood and Endothelial Markers, and Nitric Oxide Metabolites in Healthy Subjects.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rodrigo Della Méa Plentz</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Federal University of Health Science of Porto Alegre</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Federal University of Health Science of Porto Alegre</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The endothelial cell layer is responsible for the control of vascular homeostasis, a process&#xD;
      mediated by vasoconstricting and vasodilatory substances. The principal endothelium-dependent&#xD;
      vascular dilator is nitric oxide (NO), and the reduction of its synthesis or bioavailability&#xD;
      is the main cause for the development of endothelial dysfunction. The use of&#xD;
      photobiomodulation may be beneficial in several clinical situations. At the endothelial&#xD;
      level, the stimulatory effects on vascular endothelial growth factor, NO secretion, number of&#xD;
      capillaries and proliferation of endothelial cells are outstanding. The objective of this&#xD;
      study is to evaluate the effects of photobiomodulation on the arterial endothelial function&#xD;
      of healthy individuals. The study design will be a randomized, crossover, clinical trial and&#xD;
      the sample will be composed of subjects selected by the eligibility criteria, and randomly&#xD;
      randomized according to the order of intervention of the groups. The hypothesis is that at&#xD;
      the end of the protocol with photobiomodulation an increase in endothelial function and blood&#xD;
      markers of endothelial function occurs, and no tissue temperature variation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Detailed Description: The endothelial cell layer is responsible for the control of vascular&#xD;
      homeostasis, a process mediated by vasoconstricting and vasodilatory substances. The&#xD;
      principal endothelium-dependent vascular dilator is nitric oxide (NO), and the reduction of&#xD;
      its synthesis or bioavailability is the main cause for the development of endothelial&#xD;
      dysfunction. The use of photobiomodulation may be beneficial in several clinical situations.&#xD;
      At the endothelial level, the stimulatory effects on vascular endothelial growth factor, NO&#xD;
      secretion, number of capillaries and proliferation of endothelial cells are outstanding. It&#xD;
      has also been shown an increase in glutathione levels, antioxidant effect and angiogenic&#xD;
      potential, which shows a potential vascular effect, and consequently, an improvement in&#xD;
      endothelial function. The objective of this study is to evaluate the effects of&#xD;
      photobiomodulation on the arterial endothelial function of healthy individuals. The study&#xD;
      design will be a randomized, crossover, clinical trial and the sample will be composed of 16&#xD;
      healthy subjects selected by the eligibility criteria, and randomly randomized according to&#xD;
      the order of intervention of the groups. The hypothesis is that at the end of the irradiation&#xD;
      protocol with photobiomodulation an increase in endothelial function and blood markers of&#xD;
      endothelial function occurs, and no tissue temperature variation. The primary objective is to&#xD;
      evaluate the effects of photobiomodulation on the arterial endothelial function of healthy&#xD;
      individuals. The secondary objectives are: 1) To evaluate the time of blood vessel dilation&#xD;
      after photobiomodulation. 2) To evaluate the effects of photobiomodulation on blood markers&#xD;
      (hemogram) and endothelial markers (cGMP and L-arginine), and Nitric oxide (nitrite and&#xD;
      nitrate). 3) To analyze associations between markers and metabolites with endothelial&#xD;
      function due to the effects of Photobiomodulation. 3) Analyze the local temperature before&#xD;
      and after photobiomodulation. 4) Analyze the local temperature before and after the&#xD;
      measurement of Endothelial function. 5) Evaluate possible associations between blood and&#xD;
      endothelial markers, nitric oxide pathway metabolites and Endothelial function with local&#xD;
      temperature. 6) To compare the effects of energy doses and wavelenghts of photobiosmodulation&#xD;
      on endothelial function, blood and endothelial markers, and metabolites of the nitric oxide&#xD;
      pathway. The research will be developed in room 709 of the Laboratory of Physiotherapy in&#xD;
      building II, UFCSPA and, for randomization, the simple technique will be used through numbers&#xD;
      generated by a freely available software. The generation of the sequence of numbers will be&#xD;
      done by a blind researcher, after the selection of the individuals by the eligibility&#xD;
      criteria. The study will be separated in phases in according to photobiomodulation device&#xD;
      employed. Initially, we will use the laser with 658nm, power output of 10mW per point and&#xD;
      fluence of 18J, 36J e 54J per area. The individuals will be randomly assigned to: group 1&#xD;
      (energy dose of 18J), group 2 (energy dose of 36J), group 3 (energy dose of 54J), and group 4&#xD;
      (placebo). In the second phase, we will use the laser with 810nm, power density of 714 mW/cm2&#xD;
      and fluence of 30 J per spot. The individuals will be randomly assigned to: group 1 (energy&#xD;
      dose of 30J), group 2 (energy dose of 60J) and group 3 (placebo). Finally, we will measure&#xD;
      the time of blood vessel dilation after photobiomodulation with 30J and 60J. The normality of&#xD;
      the data will be evaluated by the Shapiro-Wilk test. Data with symmetrical distribution will&#xD;
      be presented as mean ± standard deviation, and data with asymmetric distribution as median&#xD;
      and interquartile range (P25 - P75). The baseline characteristics of the patients will be&#xD;
      compared by Student's t-test or Mann-Whitney when the distributions are parametric or&#xD;
      non-parametric, respectively. The categorical variables will be compared by the Chi-square&#xD;
      test. Variance Analysis (ANOVA) will be used for repeated measures for pre and&#xD;
      post-intervention data analysis, or the Mann-Whitney test (asymmetric distribution), followed&#xD;
      by Bonferroni post hoc. The Pearson or Sperman correlations will be used for possible&#xD;
      association between the analyzed variables. Statistical significance of 5% (p &lt;0.05) will be&#xD;
      observed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">September 1, 2017</start_date>
  <completion_date type="Anticipated">December 30, 2020</completion_date>
  <primary_completion_date type="Actual">December 30, 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>
    <intervention_model_description>The study will be separated in phases in according to photobiomodulation device employed. Initially, we will use the laser with 658nm, power output of 10mW per point and fluence of 18J, 36J e 54J per area. The individuals will be randomly assigned to: group 1 (energy dose of 18J), group 2 (energy dose of 36J), group 3 (energy dose of 54J), and group 4 (placebo). In the second phase, we will use the laser with 810nm, power density of 714 mW/cm2 and fluence of 30 J per spot. The individuals will be randomly assigned to: group 1 (energy dose of 30J), group 2 (energy dose of 60J) and group 3 (placebo). Finally, we will measure the time of blood vessel dilation after photobiomodulation with 30J and 60J.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in arterial endothelial function</measure>
    <time_frame>The evaluation of the arterial endothelial function will be performed 20 minutes before and 20 minutes after the intervention with photobiostimulation</time_frame>
    <description>The assessment of arterial endothelial function will be performed through the technique of flow-mediated dilatation, by high resolution ultrasound</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in body temperature</measure>
    <time_frame>The evaluation of the arterial endothelial function will be performed 15 minutes before and 15 minutes after the intervention with photobiostimulation</time_frame>
    <description>The local temperature will be evaluated by thermography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in inflammatory profile</measure>
    <time_frame>Basal blood collection (5 minutes before) and immediately after each intervention (5 minutes after)</time_frame>
    <description>The inflammatory profile will be evaluated by C-reactive protein dosage</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in arterial endothelial function (vasodilatation)</measure>
    <time_frame>Basal blood collection (5 minutes before) and immediately after each intervention (5 minutes after)</time_frame>
    <description>The vasodilatation will be evaluated by nitrite/nitrate dosage</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of blood vessel dilation</measure>
    <time_frame>The measurement of the brachial artery vasodilation time (Cruz 2016; Iida 2006) was made before (baseline), immediately after and every two minutes until completing 20 minutes of evaluation after photobiomodulation</time_frame>
    <description>The duration of the vasodilation of brachial artery after photobiomodulation</description>
  </secondary_outcome>
  <number_of_arms>9</number_of_arms>
  <enrollment type="Anticipated">16</enrollment>
  <condition>Healthy Behavior</condition>
  <arm_group>
    <arm_group_label>Phase 1 - Low level laser therapy - 1 (G1)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Low level laser therapy with energy dose of 18J will be applied on left brachial artery of the subject.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1 - Low level laser therapy - 1 (G2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Low level laser therapy with energy dose of 36J will be applied on left brachial artery of the subject.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1 - Low level laser therapy - 1 (G3)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Low level laser therapy with energy dose of 54J will be applied on left brachial artery of the subject.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1 - Placebo low level laser therapy - 1 (G4)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Low level laser therapy with equipment turn off (placebo) be applied on left brachial artery of the subject.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2 - Low level laser therapy - 2 (G1)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Low level laser therapy with energy dose of 30J will be applied on left brachial artery of the subject.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2 - Low level laser therapy - 2 (G2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Low level laser therapy with energy dose of 60J will be applied on left brachial artery of the subject.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2 - Placebo low level laser therapy - 2 (G3)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Low level laser therapy with equipment turn off (placebo) be applied on left brachial artery of the subject.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 3 - Low level laser therapy - 3 (G1)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Low level laser therapy with energy dose of 30J will be applied on left brachial artery of the subject.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 3 - Low level laser therapy - 3(G2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Low level laser therapy with energy dose of 60J will be applied on left brachial artery of the subject.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Low level laser therapy - 1</intervention_name>
    <description>In the phase 1, the low level laser therapy will be performed with the Fluence device (HTM, Brasil) and the probe from the same manufacturer. For the interventions in groups G1, G2 and G3 (photobiomodulation) will be used, respectively, the energy doses of 18J, 36J and 54J. A 658nm wavelength with an output power of 10mW will be used. Group 4 intervention (placebo photobiomodulation) will be performed with the application of the device turned off. Each intervention will be performed in one day, with an interval of two days between each intervention. Photobiomodulation will be performed on the region of the radial and ulnar arteries of the left arm of each individual. The laser probe will be placed in direct contact with the skin.</description>
    <arm_group_label>Phase 1 - Low level laser therapy - 1 (G1)</arm_group_label>
    <arm_group_label>Phase 1 - Low level laser therapy - 1 (G2)</arm_group_label>
    <arm_group_label>Phase 1 - Low level laser therapy - 1 (G3)</arm_group_label>
    <arm_group_label>Phase 1 - Placebo low level laser therapy - 1 (G4)</arm_group_label>
    <other_name>Photobiomodulation</other_name>
    <other_name>LLLT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Low level laser therapy - 2</intervention_name>
    <description>In the phase 2, the low level laser therapy will be performed with the Thor DD2 (London, UK) and the cluster probe from the same manufacturer. For the interventions in groups G1 and G2 (photobiomodulation) will be used, respectively, the energy doses of 30J and 60J. A 810nm wavelength and an output power of 200mW will be used. Group 3 intervention (placebo photobiomodulation) will be performed with the application of the device turned off. Each intervention will be performed in one day, with an interval of two days between each intervention. Photobiomodulation will be performed on the region of the radial and ulnar arteries of the left arm of each individual. The laser probe will be placed in direct contact with the skin.</description>
    <arm_group_label>Phase 2 - Low level laser therapy - 2 (G1)</arm_group_label>
    <arm_group_label>Phase 2 - Low level laser therapy - 2 (G2)</arm_group_label>
    <arm_group_label>Phase 2 - Placebo low level laser therapy - 2 (G3)</arm_group_label>
    <other_name>Photobiomodulation</other_name>
    <other_name>LLLT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Low level laser therapy - 3</intervention_name>
    <description>In the phase 3, the low level laser therapy will be performed with the Thor DD2 (London, UK) and the cluster probe from the same manufacturer. For the interventions in groups G1 and G2 (photobiomodulation) will be used, respectively, the energy doses of 30J and 60J. A 810nm wavelength and an output power of 200mW will be used. Each intervention will be performed in one day, with an interval of two days between each intervention. Photobiomodulation will be performed on the region of the radial and ulnar arteries of the left arm of each individual. The laser probe will be placed in direct contact with the skin.</description>
    <arm_group_label>Phase 3 - Low level laser therapy - 3 (G1)</arm_group_label>
    <arm_group_label>Phase 3 - Low level laser therapy - 3(G2)</arm_group_label>
    <other_name>Photobiomodulation</other_name>
    <other_name>LLLT</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age between 18-40 years&#xD;
&#xD;
          -  Body mass index (BMI: kg / m2) lower than 30&#xD;
&#xD;
          -  Absence of symptoms of musculoskeletal disorders&#xD;
&#xD;
          -  No use of medications&#xD;
&#xD;
          -  Non-smokers and / or alcoholics&#xD;
&#xD;
          -  Absence of previous diagnosis of diseases Rheumatological, cardiovascular, renal,&#xD;
             metabolic, neurological, oncological, immunological, hematological, psychiatric or&#xD;
             cognitive.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        On the days of evaluation and intervention:&#xD;
&#xD;
          -  Individuals who performed high intensity physical activity in the previous 72 hours&#xD;
&#xD;
          -  Individuals who had an inflammatory response (&gt; 3 mg / dL, fibrinogen &lt;200 or&gt; 400mg /&#xD;
             dL) or leukocytosis (&gt; 11,000 x103 / Mm3)&#xD;
&#xD;
          -  Individuals who have consumed caffeine, juices or citrus fruits, high-fat foods and&#xD;
             alcohol in the 12 hours prior to the test&#xD;
&#xD;
          -  Individuals who are not fasting for 12 hours&#xD;
&#xD;
          -  Individuals who have used anti-inflammatory, antipyretic or analgesic drugs&#xD;
&#xD;
          -  Individuals who having an arterial diameter &lt;0.25 mm or&gt; 5.0 mm&#xD;
&#xD;
          -  Individuals with present endothelial dysfunction evaluated by the FMD technique&#xD;
             (dilation &lt;8%).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rodrigo DM Plentz, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Federal University of Health Science of Porto Alegre</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Melina Hauck, Me</last_name>
    <role>Principal Investigator</role>
    <affiliation>Federal University of Health Science of Porto Alegre</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jociane Schardong, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Federal University of Health Science of Porto Alegre</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Camila B Bozzetto, Me</last_name>
    <role>Principal Investigator</role>
    <affiliation>Federal University of Health Science of Porto Alegre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Federal University of Health Science of Porto Alegre (UFCSPA)</name>
      <address>
        <city>Porto Alegre</city>
        <state>Rio Grande Do Sul</state>
        <zip>90050170</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>May 18, 2017</study_first_submitted>
  <study_first_submitted_qc>August 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 17, 2017</study_first_posted>
  <last_update_submitted>March 20, 2020</last_update_submitted>
  <last_update_submitted_qc>March 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 24, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Federal University of Health Science of Porto Alegre</investigator_affiliation>
    <investigator_full_name>Rodrigo Della Méa Plentz</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Phototherapy</keyword>
  <keyword>Laser Therapy</keyword>
  <keyword>Endothelium-Dependent</keyword>
  <keyword>Vascular Endothelium</keyword>
  <keyword>Low Intensity Light Therapy</keyword>
  <keyword>Relaxing Factors</keyword>
  <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/NCT03252184
org study id: PBMLLLT
nct id: NCT03252184
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The endothelial cell layer is responsible for the control of vascular homeostasis, a process
      mediated by vasoconstricting and vasodilatory substances. The principal endothelium-dependent
      vascular dilator is nitric oxide (NO), and the reduction of its synthesis or bioavailability
      is the main cause for the development of endothelial dysfunction. The use of
      photobiomodulation may be beneficial in several clinical situations. At the endothelial
      level, the stimulatory effects on vascular endothelial growth factor, NO secretion, number of
      capillaries and proliferation of endothelial cells are outstanding. The objective of this
      study is to evaluate the effects of photobiomodulation on the arterial endothelial function
      of healthy individuals. The study design will be a randomized, crossover, clinical trial and
      the sample will be composed of subjects selected by the eligibility criteria, and randomly
      randomized according to the order of intervention of the groups. The hypothesis is that at
      the end of the protocol with photobiomodulation an increase in endothelial function and blood
      markers of endothelial function occurs, and no tissue temperature variation.
Detailed Description: The endothelial cell layer is responsible for the control of vascular
      homeostasis, a process mediated by vasoconstricting and vasodilatory substances. The
      principal endothelium-dependent vascular dilator is nitric oxide (NO), and the reduction of
      its synthesis or bioavailability is the main cause for the development of endothelial
      dysfunction. The use of photobiomodulation may be beneficial in several clinical situations.
      At the endothelial level, the stimulatory effects on vascular endothelial growth factor, NO
      secretion, number of capillaries and proliferation of endothelial cells are outstanding. It
      has also been shown an increase in glutathione levels, antioxidant effect and angiogenic
      potential, which shows a potential vascular effect, and consequently, an improvement in
      endothelial function. The objective of this study is to evaluate the effects of
      photobiomodulation on the arterial endothelial function of healthy individuals. The study
      design will be a randomized, crossover, clinical trial and the sample will be composed of 16
      healthy subjects selected by the eligibility criteria, and randomly randomized according to
      the order of intervention of the groups. The hypothesis is that at the end of the irradiation
      protocol with photobiomodulation an increase in endothelial function and blood markers of
      endothelial function occurs, and no tissue temperature variation. The primary objective is to
      evaluate the effects of photobiomodulation on the arterial endothelial function of healthy
      individuals. The secondary objectives are: 1) To evaluate the time of blood vessel dilation
      after photobiomodulation. 2) To evaluate the effects of photobiomodulation on blood markers
      (hemogram) and endothelial markers (cGMP and L-arginine), and Nitric oxide (nitrite and
      nitrate). 3) To analyze associations between markers and metabolites with endothelial
      function due to the effects of Photobiomodulation. 3) Analyze the local temperature before
      and after photobiomodulation. 4) Analyze the local temperature before and after the
      measurement of Endothelial function. 5) Evaluate possible associations between blood and
      endothelial markers, nitric oxide pathway metabolites and Endothelial function with local
      temperature. 6) To compare the effects of energy doses and wavelenghts of photobiosmodulation
      on endothelial function, blood and endothelial markers, and metabolites of the nitric oxide
      pathway. The research will be developed in room 709 of the Laboratory of Physiotherapy in
      building II, UFCSPA and, for randomization, the simple technique will be used through numbers
      generated by a freely available software. The generation of the sequence of numbers will be
      done by a blind researcher, after the selection of the individuals by the eligibility
      criteria. The study will be separated in phases in according to photobiomodulation device
      employed. Initially, we will use the laser with 658nm, power output of 10mW per point and
      fluence of 18J, 36J e 54J per area. The individuals will be randomly assigned to: group 1
      (energy dose of 18J), group 2 (energy dose of 36J), group 3 (energy dose of 54J), and group 4
      (placebo). In the second phase, we will use the laser with 810nm, power density of 714 mW/cm2
      and fluence of 30 J per spot. The individuals will be randomly assigned to: group 1 (energy
      dose of 30J), group 2 (energy dose of 60J) and group 3 (placebo). Finally, we will measure
      the time of blood vessel dilation after photobiomodulation with 30J and 60J. The normality of
      the data will be evaluated by the Shapiro-Wilk test. Data with symmetrical distribution will
      be presented as mean ± standard deviation, and data with asymmetric distribution as median
      and interquartile range (P25 - P75). The baseline characteristics of the patients will be
      compared by Student's t-test or Mann-Whitney when the distributions are parametric or
      non-parametric, respectively. The categorical variables will be compared by the Chi-square
      test. Variance Analysis (ANOVA) will be used for repeated measures for pre and
      post-intervention data analysis, or the Mann-Whitney test (asymmetric distribution), followed
      by Bonferroni post hoc. The Pearson or Sperman correlations will be used for possible
      association between the analyzed variables. Statistical significance of 5% (p <0.05) will be
      observed.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: The study will be separated in phases in according to photobiomodulation device employed. Initially, we will use the laser with 658nm, power output of 10mW per point and fluence of 18J, 36J e 54J per area. The individuals will be randomly assigned to: group 1 (energy dose of 18J), group 2 (energy dose of 36J), group 3 (energy dose of 54J), and group 4 (placebo). In the second phase, we will use the laser with 810nm, power density of 714 mW/cm2 and fluence of 30 J per spot. The individuals will be randomly assigned to: group 1 (energy dose of 30J), group 2 (energy dose of 60J) and group 3 (placebo). Finally, we will measure the time of blood vessel dilation after photobiomodulation with 30J and 60J.
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Change in arterial endothelial function
time frame: The evaluation of the arterial endothelial function will be performed 20 minutes before and 20 minutes after the intervention with photobiostimulation
description: The assessment of arterial endothelial function will be performed through the technique of flow-mediated dilatation, by high resolution ultrasound
measure: Change in body temperature
time frame: The evaluation of the arterial endothelial function will be performed 15 minutes before and 15 minutes after the intervention with photobiostimulation
description: The local temperature will be evaluated by thermography
measure: Change in inflammatory profile
time frame: Basal blood collection (5 minutes before) and immediately after each intervention (5 minutes after)
description: The inflammatory profile will be evaluated by C-reactive protein dosage
measure: Change in arterial endothelial function (vasodilatation)
time frame: Basal blood collection (5 minutes before) and immediately after each intervention (5 minutes after)
description: The vasodilatation will be evaluated by nitrite/nitrate dosage
measure: Time of blood vessel dilation
time frame: The measurement of the brachial artery vasodilation time (Cruz 2016; Iida 2006) was made before (baseline), immediately after and every two minutes until completing 20 minutes of evaluation after photobiomodulation
description: The duration of the vasodilation of brachial artery after photobiomodulation
arm group label: Phase 1 - Low level laser therapy - 1 (G1)
arm group type: Experimental
description: Low level laser therapy with energy dose of 18J will be applied on left brachial artery of the subject.
arm group label: Phase 1 - Low level laser therapy - 1 (G2)
arm group type: Experimental
description: Low level laser therapy with energy dose of 36J will be applied on left brachial artery of the subject.
arm group label: Phase 1 - Low level laser therapy - 1 (G3)
arm group type: Experimental
description: Low level laser therapy with energy dose of 54J will be applied on left brachial artery of the subject.
arm group label: Phase 1 - Placebo low level laser therapy - 1 (G4)
arm group type: Placebo Comparator
description: Low level laser therapy with equipment turn off (placebo) be applied on left brachial artery of the subject.
arm group label: Phase 2 - Low level laser therapy - 2 (G1)
arm group type: Experimental
description: Low level laser therapy with energy dose of 30J will be applied on left brachial artery of the subject.
arm group label: Phase 2 - Low level laser therapy - 2 (G2)
arm group type: Experimental
description: Low level laser therapy with energy dose of 60J will be applied on left brachial artery of the subject.
arm group label: Phase 2 - Placebo low level laser therapy - 2 (G3)
arm group type: Placebo Comparator
description: Low level laser therapy with equipment turn off (placebo) be applied on left brachial artery of the subject.
arm group label: Phase 3 - Low level laser therapy - 3 (G1)
arm group type: Experimental
description: Low level laser therapy with energy dose of 30J will be applied on left brachial artery of the subject.
arm group label: Phase 3 - Low level laser therapy - 3(G2)
arm group type: Experimental
description: Low level laser therapy with energy dose of 60J will be applied on left brachial artery of the subject.
intervention type: Device
intervention name: Low level laser therapy - 1
description: In the phase 1, the low level laser therapy will be performed with the Fluence device (HTM, Brasil) and the probe from the same manufacturer. For the interventions in groups G1, G2 and G3 (photobiomodulation) will be used, respectively, the energy doses of 18J, 36J and 54J. A 658nm wavelength with an output power of 10mW will be used. Group 4 intervention (placebo photobiomodulation) will be performed with the application of the device turned off. Each intervention will be performed in one day, with an interval of two days between each intervention. Photobiomodulation will be performed on the region of the radial and ulnar arteries of the left arm of each individual. The laser probe will be placed in direct contact with the skin.
arm group label: Phase 1 - Low level laser therapy - 1 (G1)
arm group label: Phase 1 - Low level laser therapy - 1 (G2)
arm group label: Phase 1 - Low level laser therapy - 1 (G3)
arm group label: Phase 1 - Placebo low level laser therapy - 1 (G4)
other name: Photobiomodulation
other name: LLLT
intervention type: Device
intervention name: Low level laser therapy - 2
description: In the phase 2, the low level laser therapy will be performed with the Thor DD2 (London, UK) and the cluster probe from the same manufacturer. For the interventions in groups G1 and G2 (photobiomodulation) will be used, respectively, the energy doses of 30J and 60J. A 810nm wavelength and an output power of 200mW will be used. Group 3 intervention (placebo photobiomodulation) will be performed with the application of the device turned off. Each intervention will be performed in one day, with an interval of two days between each intervention. Photobiomodulation will be performed on the region of the radial and ulnar arteries of the left arm of each individual. The laser probe will be placed in direct contact with the skin.
arm group label: Phase 2 - Low level laser therapy - 2 (G1)
arm group label: Phase 2 - Low level laser therapy - 2 (G2)
arm group label: Phase 2 - Placebo low level laser therapy - 2 (G3)
other name: Photobiomodulation
other name: LLLT
intervention type: Device
intervention name: Low level laser therapy - 3
description: In the phase 3, the low level laser therapy will be performed with the Thor DD2 (London, UK) and the cluster probe from the same manufacturer. For the interventions in groups G1 and G2 (photobiomodulation) will be used, respectively, the energy doses of 30J and 60J. A 810nm wavelength and an output power of 200mW will be used. Each intervention will be performed in one day, with an interval of two days between each intervention. Photobiomodulation will be performed on the region of the radial and ulnar arteries of the left arm of each individual. The laser probe will be placed in direct contact with the skin.
arm group label: Phase 3 - Low level laser therapy - 3 (G1)
arm group label: Phase 3 - Low level laser therapy - 3(G2)
other name: Photobiomodulation
other name: LLLT
criteria: 
gender: All
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Rodrigo DM Plentz, PhD
role: Study Director
affiliation: Federal University of Health Science of Porto Alegre
last name: Melina Hauck, Me
role: Principal Investigator
affiliation: Federal University of Health Science of Porto Alegre
last name: Jociane Schardong, PhD
role: Principal Investigator
affiliation: Federal University of Health Science of Porto Alegre
last name: Camila B Bozzetto, Me
role: Principal Investigator
affiliation: Federal University of Health Science of Porto Alegre
facility: 
country: Brazil
responsible party type: Sponsor-Investigator
investigator affiliation: Federal University of Health Science of Porto Alegre
investigator full name: Rodrigo Della Méa Plentz
investigator title: Principal Investigator
sharing ipd: No