Impact of Citrulline and Arginine Supplementation on the Post-exercise Hypotension (PEH) (PEH)

December 22, 2017 updated by: Juliano Casonatto

Impact of L-citrulline Associated With L-arginine Supplementation on the Post-exercise Hypotension in Normotensives and Hypertensives

Post-exercise hypotension (PEH) is a established phenomenon as one of the non-pharmacological ways of reducing blood pressure, producing important impacts, particularly in hypertensive individuals. However, the factors involved in the magnitude and duration of this effect are relatively little studied. Thus, the bioavailability of vasodilatation mediators may maximize the duration and magnitude of PEH. In this sense, the objective of the present project will be to verify the impact of L-citrulline associated with L-arginine supplementation on the acute blood pressure response after an aerobic exercise session. Approximately 80 adults (40 normotensive and 40 hypertensive) will be selected. The sample will be submitted to measurements of body mass, height and resting blood pressure. After the minimum interval of 48 h, subjects will be randomly submitted to four experimental situations (exercise/L-citrulline, exercise/L-arginine, exercise/placebo, exercise/L-citrulline + L-arginine). The exercise sessions (40 min in treadmill at 60% of FCres) will be performed with a minimum interval of 48 h. After each session, the blood pressure of the sample will be recorded during 24 hours. For data analysis, blood pressure values will be plotted in average of the wakefulness and average of the sleep periods and average of the 24 hours. The comparisons will be made through the ANOVA (repeated measures), following the recommended assumptions. It is hoped that the results of this project will collaborate to the knowledge regarding non-pharmacological models aimed at the prevention and treatment of hypertension in normotensive and hypertensive patients.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Participants After sample size calculation (see statistical analysis session), 40 hypertensives and 40 normotensive sedentaries will be recruited to this study. All volunteers (both sexes) will be adults without osteoarticular disabilities and they will need a medical authorization to physical exercise practice. Participants will be recruited from an exercise program project linked to the university that offered stretching and functional exercises sessions to the external community. The study follow the Declaration of Helsinki and the Institutional Ethics Committee approved all experimental procedures and protocols. Each participant will be fully informed of all potential risks and experimental procedures, after which, informed written consent will be signed. Table 1 shows the basics characteristics of the participants.

Study design A double-blind crossover randomized clinical trial will be conducted. After the minimum interval (48 hours), the subjects will be randomly (using a random number table - https://www.random.org/) submitted to four experimental situations (exercise/L-citrulline, exercise/L-arginine, exercise/placebo, exercise/L-citrulline + L-arginine). The participants will ingested a sachet, which contained L-citrulline malate (6 grams) or L-arginine (8 grams) or placebo (6 grams of corn starch) dissolved in water.

The substances will be ingested 120 minutes before the experimental or control session. Anthropometric measures will be taken before the rest period. The exercise session consisted of 5 min to warm up (50% of 65% HRreserve) and 40 minutes of run/walk at 60-70% HRreserve (or 12-14 ratings of perceived exertion [RPE](1) if take some beta-blocker medicines) in a treadmill. This will be followed by a progressive cooldown (5 minutes). In the control session, the participants will be remained seated in a quiet room for 40 min.

After the exercise/control sessions, the blood pressure will be measured every 10 minutes over the course of 60 minutes and the heart rate variability will be recorded continuously for 60 minutes (laboratorial phase). Then, 15 minutes will be given to the participants to take a shower and change the clothes before the ambulatory blood pressure device be attached on their arm. The ambulatory blood pressure will be recorded over 24 hours. In the next day, the participants will be asked to return to the laboratory to remove the device.

Anthropometry The weight will be measured by the digital anthropometric scale (Urano, OS 180A, Canoas, Brasil), with accuracy of 0.1kg and height will be measured by stadiometer with accuracy of 0.1cm, in accordance with the procedures described by Gordon et al (2). The body mass index (BMI) will be defined as the body mass (kg) divided by the square of the body height.

Office Blood Pressure (laboratorial phase) The office blood pressure measurements will be taken with oscillometric device (Omron MX3 Plus, Bannockburn, EUA) previously validated for clinic measures in adults (3). Firstly, the participants remained seated (rest period) in calm, quiet and thermoneutral (22°-24°C) environment for 20 min. The blood pressure will be measured three times during the rest period (at 10 min, 15 min and 20 min). The rest blood pressure value will be considered as the average of these three measurements. Immediately following the sessions (exercise or control), the blood pressure will be measured in a quiet environment during 60 minutes. The blood pressure measurements will be taken according to the American Heart Association recommendations (4).

Heart rate variability measures The heart rate variability will be monitored during the rest period using a cardiac monitor (Polar RS800CX, Kempele, Finlândia) previously validated (5). The recorded R-R intervals will be transferred to a computer using a specific software (Polar Pro-Trainer software, Kempele, Finlândia). The Fast Fourier Transformation will be applied to quantify the low and high frequencies in to normalized units, in accordance with Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology (6). The participants will be taking beta-blockers will be excluded of this analysis.

The time domain analisys will be obtained by SDNN (standard deviation of the NN interval), RMSSD (the square root of the mean of the sum of the squares of differences between adjacent NN intervals), pNN50 (NN50 count divided by the total number of all NN intervals), indexes. The range interval analysis will be 5 min (rest, previous exercise) and 30 min (post-exercise - laboratorial phase) using the Kubios HRV, version 2.2 (Kuopio, Finlândia).

Ambulatorial blood pressure measures (ambulatorial phase) The ambulatorial blood pressure measurements will be taken with oscillometric device (Dyna-MAPA - São Paulo, Brazil) attached on the left arm, always by the same investigator, in accordance with procedures described by American Heart Association (4). The participants will be instructioned to keep the arm stand during the measures. The device will be calibrated by direct comparison with mercury sphygmomanometer, by trained technical person, in agreement with recommendations (4).

The monitor will be setting to register the systolic and diastolic blood pressure and heart rate every 20 minutes during "daytime" (08:00am to 11:00pm) and every 30 minutes during "night-time" (11:00pm to 08:00am) to reduce sleep disturbs. The device screen will be electronically blinded to avoid feedback. All participants will be instructed to register and reported their sleep time in a diary on the day after.

The data will be recorded in the device memory, then they will be send to a computer using specific software (Aplicação Dyna Mapa - Version 5.0.382.12) for analysis. The average of the valid readings will be above 90% for all participants.

Statistical analysis Assuming a standard deviation of 5 mmHg(7) for the systolic blood pressure, an alpha of 5% and a desired statistical power of 80% for detecting a minimum difference of 7 mmHg (7) required 10 subjects in each group.

The datas will be presented in the text as mean and standard error. The sphericity Mauchly´s test will be applied. Greenhouse-Geisser correction will be used if necessary. Then, these datas will be compared with a one-factor repeated measures general linear model (GLM). Fisher multiple comparisons will be employed to examine differences between pairs of trials.

The ambulatory blood pressure will be analysed as awake, sleep and 24 hours of monitoring. Statistical significance will be defined as P<0.05. The statistical analysis will be generated using SPSS, version 20, system for windows.

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Brazil
    • Parana
      • Londrina, Parana, Brazil, 86025-170
        • Recruiting
        • Juliano Casonatto
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Hypertensive and Normotensive, without osteoarticular disabilities and medical authorization to physical exercise practice.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: L-citrulline & L-arginine
L-citrulline (6 grams) L-arginine (8 grams)
Dietary supplement: L-citrulline + L-arginine
L-citrulline + L-arginine - sachet dissolved in water
Active Comparator: L-citrulline & Placebo
L-citrulline (6 grams) Placebo (6 grams)
Dietary supplement: L-citrulline
L-citrulline - sachet dissolved in water
Dietary supplement: Placebo
Placebo (corn starch) - sachet dissolved in water
Active Comparator: L-arginine & Placebo
L-arginine (8 grams) Placebo (6 grams)
Dietary supplement: Placebo
Placebo (corn starch) - sachet dissolved in water
Dietary supplement: L-arginine
L-arginine - sachet dissolved in water
Active Comparator: Placebo
Placebo (6 grams)
Dietary supplement: Placebo
Placebo (corn starch) - sachet dissolved in water

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ambulatorial Blood Pressure Monitoring
Time Frame: 24 hours
The ambulatorial blood pressure measurements will be taken with oscillometric device (Dyna-MAPA - São Paulo, Brazil) attached on the left arm. The participants will received instructions to keep the arm stand during the measures. The monitor will be setting to register the systolic and diastolic blood pressure and heart rate every 20 minutes during "daytime" (08:00am to 11:00pm) and every 30 minutes during "night-time" (11:00pm to 08:00am) to reduce sleep disturbs. The device screen will be electronically blinded to avoid feedback. The metric measures will be reported by millimeters of mercury (mmHg).
24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Juliano Casonatto

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

January 2, 2018

Primary Completion (Anticipated)

January 31, 2018

Study Completion (Anticipated)

February 28, 2018

Study Registration Dates

First Submitted

December 14, 2017

First Submitted That Met QC Criteria

December 14, 2017

First Posted (Actual)

December 20, 2017

Study Record Updates

Last Update Posted (Actual)

December 27, 2017

Last Update Submitted That Met QC Criteria

December 22, 2017

Last Verified

December 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016-0108 (Other Identifier: M D Anderson Cancer Center)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Hypertension

Clinical Trials on L-citrulline + L-arginine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Hungary

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe