Clinical trial NCT03252184: Effects of Photobiomodulation on Endothelial Function in Healthy Subjects
Official title: Effects of Photobiomodulation on Endothelial Function, Blood and Endothelial Markers, and Nitric Oxide Metabolites in Healthy Subjects.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Healthy Behavior
Keywords: Phototherapy
Laser Therapy
Endothelium-Dependent
Vascular Endothelium
Low Intensity Light Therapy
Relaxing Factors
Lead sponsor: Federal University of Health Science of Porto Alegre
Sponsor class: OTHER
Collaborators: name: Federal University of Health Science of Porto Alegre
First posted: 2017-08-17
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

* Age between 18-40 years
* Body mass index (BMI: kg / m2) lower than 30
* Absence of symptoms of musculoskeletal disorders
* No use of medications
* Non-smokers and / or alcoholics
* Absence of previous diagnosis of diseases Rheumatological, cardiovascular, renal, metabolic, neurological, oncological, immunological, hematological, psychiatric or cognitive.

Exclusion Criteria:

On the days of evaluation and intervention:

* Individuals who performed high intensity physical activity in the previous 72 hours
* Individuals who had an inflammatory response (\> 3 mg / dL, fibrinogen \<200 or\> 400mg / dL) or leukocytosis (\> 11,000 x103 / Mm3)
* Individuals who have consumed caffeine, juices or citrus fruits, high-fat foods and alcohol in the 12 hours prior to the test
* Individuals who are not fasting for 12 hours
* Individuals who have used anti-inflammatory, antipyretic or analgesic drugs
* Individuals who having an arterial diameter \<0.25 mm or\> 5.0 mm
* Individuals with present endothelial dysfunction evaluated by the FMD technique (dilation \<8%).

Primary outcomes:
measure: Change in arterial endothelial function
timeFrame: The evaluation of the arterial endothelial function will be performed 20 minutes before and 20 minutes after the intervention with photobiostimulation
Secondary outcomes:
measure: Change in body temperature
timeFrame: The evaluation of the arterial endothelial function will be performed 15 minutes before and 15 minutes after the intervention with photobiostimulation
measure: Change in inflammatory profile
timeFrame: Basal blood collection (5 minutes before) and immediately after each intervention (5 minutes after)
measure: Change in arterial endothelial function (vasodilatation)
timeFrame: Basal blood collection (5 minutes before) and immediately after each intervention (5 minutes after)
measure: Time of blood vessel dilation
timeFrame: 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
Other outcomes:
Locations:
city: Porto Alegre
country: Brazil
facility: Federal University of Health Science of Porto Alegre (UFCSPA)
state: Rio Grande Do Sul
Study officials:
affiliation: Federal University of Health Science of Porto Alegre
name: Rodrigo DM Plentz, PhD
role: STUDY_DIRECTOR
affiliation: Federal University of Health Science of Porto Alegre
name: Melina Hauck, Me
role: PRINCIPAL_INVESTIGATOR
affiliation: Federal University of Health Science of Porto Alegre
name: Jociane Schardong, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Federal University of Health Science of Porto Alegre
name: Camila B Bozzetto, Me
role: PRINCIPAL_INVESTIGATOR
References: