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HypertensionPEHNCT03378596

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

A study testing L-citrulline + L-arginine, L-arginine and L-citrulline in people with Hypertension, run by Juliano Casonatto at 1 site in Brazil.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Any ageHealthy volunteers can take part
Conditions the study is for
Hypertension
What is being tested?
L-citrulline + L-arginine, L-arginine and L-citrulline
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
20 participants
Where
1 siteBrazil
Study dates
2 Jan 2018to 28 Feb 2018
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult, Older adult

Who may be able to join

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

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

Juliano Casonatto, PhD contact

55-43-999840790

juliano2608@hotmail.com

Brazil1 site, 1 recruiting
  • Juliano Casonatto

    Londrina, Paraná, 86025-170

    Juliano Casonatto, PhD, 55-43-999840790, juliano2608@hotmail.com

    Recruiting

Other trials in Brazil

About this study

Official title: 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.

Read the 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.

Conditions
Hypertension
Being tested
L-citrulline + L-arginine, L-arginine, L-citrulline, Placebo
Keywords
Post-Exercise Hypotension, Exercise, Arginine, Citrulline
Medical subject headings
Hypertension, Post-Exercise Hypotension, Motor Activity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • L-citrulline + L-arginineDietary supplement

    L-citrulline + L-arginine - sachet dissolved in water

  • L-arginineDietary supplement

    L-arginine - sachet dissolved in water

  • L-citrullineDietary supplement

    L-citrulline - sachet dissolved in water

  • PlaceboDietary supplement

    Placebo (corn starch) - sachet dissolved in water

Study groups in NCT03378596
Study groupRoleWhat they receive
L-citrulline & L-arginineExperimentalL-citrulline (6 grams) L-arginine (8 grams)
Receives: Dietary Supplement: L-citrulline + L-arginine
L-citrulline & PlaceboActive comparatorL-citrulline (6 grams) Placebo (6 grams)
Receives: Dietary Supplement: L-citrulline; Dietary Supplement: Placebo
L-arginine & PlaceboActive comparatorL-arginine (8 grams) Placebo (6 grams)
Receives: Dietary Supplement: L-arginine; Dietary Supplement: Placebo
PlaceboActive comparatorPlacebo (6 grams)
Receives: Dietary Supplement: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Ambulatorial Blood Pressure Monitoring

    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).

    Measured: 24 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Dec 2017
  2. Study start2 Jan 2018 (estimated)
  3. Primary completion31 Jan 2018 (estimated)
  4. Study completion28 Feb 2018 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03378596
Sponsor's protocol ID
2016-0108
Acronym
PEH
Status last verified
Dec 2017
First submitted
14 Dec 2017
Last updated
27 Dec 2017
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Borg G. Borg's Perceived Exertion and Pain Scales. Champaign: Human Kinetics; 1998.

  • Gordon CC, Chumlea WC, Roche AF. Stature, recumbent length, and weight. Lohman TG, Roche AF, Martorell R, editors. Champaign: Human Kinetics Books; 1988. 3-8 p.

  • Coleman A, Freeman P, Steel S, Shennan A. Validation of the Omron MX3 Plus oscillometric blood pressure monitoring device according to the European Society of Hypertension international protocol. Blood Press Monit. 2005 Jun;10(3):165-8. doi: 10.1097/00126097-200506000-00009.

    PubMed 15923819
  • Pickering TG, Hall JE, Appel LJ, Falkner BE, Graves J, Hill MN, Jones DW, Kurtz T, Sheps SG, Roccella EJ; Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Recommendations for blood pressure measurement in humans and experimental animals: Part 1: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Hypertension. 2005 Jan;45(1):142-61. doi: 10.1161/01.HYP.0000150859.47929.8e. Epub 2004 Dec 20.

    PubMed 15611362
  • Quintana DS, Heathers JA, Kemp AH. On the validity of using the Polar RS800 heart rate monitor for heart rate variability research. Eur J Appl Physiol. 2012 Dec;112(12):4179-80. doi: 10.1007/s00421-012-2453-2. Epub 2012 Jul 13. No abstract available.

    PubMed 22790488
  • Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation. 1996 Mar 1;93(5):1043-65. No abstract available.

    PubMed 8598068
  • Casonatto J, Tinucci T, Dourado AC, Polito M. Cardiovascular and autonomic responses after exercise sessions with different intensities and durations. Clinics (Sao Paulo). 2011;66(3):453-8. doi: 10.1590/s1807-59322011000300016.

    PubMed 21552672
  • Domingues V, Cavalari JV, Grandolfi K, Aguiar AF, Borghi SM, Casonatto J. Acute Effects of Citrulline Malate Supplementation on Nocturnal Blood Pressure Dipping After Exercise in Hypertensive Patients: A Randomized, Placebo-Controlled Trial. J Diet Suppl. 2024;21(6):868-880. doi: 10.1080/19390211.2024.2414052. Epub 2024 Oct 10.

    PubMed 39385595

Questions about this trial

What is this clinical trial studying?

A study testing L-citrulline + L-arginine, L-arginine and L-citrulline in people with Hypertension, run by Juliano Casonatto at 1 site in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 27 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Juliano Casonatto, PhD (55-43-999840790, juliano2608@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Ambulatorial Blood Pressure Monitoring (time frame: 24 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03378596, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2017.

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