Effect of L-citrulline and HIIT on Arterial Stiffness, Body Composition, and Lipid Profile in Adolescents with Steatosis Associated with Metabolic Dysfunction (MASLD)

December 16, 2024 updated by: Ma Eugenia Garay Sevilla, Universidad de Guanajuato
Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) accelerate the appearance of arterial stiffness due to inflammatory and oxidative stress mechanisms producing increased vascular tone and increasing the risk of cardiovascular disease. This arterial stiffness can be measured through pulse wave velocity (PWV). Obesity and MAFLD have multifactorial components, high fructose diet and sedentary lifestyle are causing the onset of these diseases earlier in life such as in adolescence. L-citrulline, a non-protein amino acid, has shown positive effects on improving nitric oxide synthesis which improves endothelial function, as well as results on the metabolic profile in MASLD. High intensity interval training (HIIT) has also shown benefits on endothelial function improving the metabolic profile of people with obesity and MASLD with the advantage of decreasing the time required to perform the physical activity. A clinical study will be conducted with 45 adolescents (15-19 years old) with MASLD and the participants will be divided into 3 groups to perform HIIT and supplement with citrulline or placebo for 12 weeks.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The investigators hypothesize that citrulline and HIIT have additive effects on endothelial function in people with obesity and MASLD, in addition to improving metabolic, lipid and hepatic steatosis profile. the researcher´s aim is to evaluate the effect of citrulline and HIIT on arterial stiffness assessed by PWV in adolescents with MASLD. For this the investigators will perform a randomized, double-blind clinical study in 45 adolescents with MASLD and obesity, who will be supplemented with 6 g per day with L-citrulline or placebo (Carboxymethylcellulose) and will perform HIIT sessions for 12 weeks. At the beginning and at the end of the intervention, the level of arterial stiffness by means of PWV, body composition, biochemical and metabolic data, as well as the degree of hepatic steatosis will be evaluated.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
43

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Locations

  • Mexico
    • Guanajuato
      • León, Guanajuato, Mexico, 37000
        • Universidad de Guanajuato

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

15 years to 19 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis of obesity and metabolic associated-dysfunction steatotic liver disease associated with (MASLD) and with moderate or severe steatosis
  • History of physical inactivity
  • They should not be under treatment with any dietary supplement or polyvitamins for weight loss at least 6 months before the study.
  • They should not be smokers.
  • Not have a diagnosis of any chronic degenerative disease
  • Adolescents without fracture or musculoskeletal injury
  • Patients without surgical procedures at least 1 month prior to the protocol.
  • Women who are not pregnant or use oral contraceptives

Exclusion Criteria:

  • Participants who do not complete at least 80% of the training sessions.
  • Participants who miss 2 consecutive weeks of training.
  • Who do not ingest the L-citrulline supplement or placebo.
  • Participants who present allergy or intolerance to L-citrulline.
  • Participants who present any injury during the intervention period that prevents them from performing the training.

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: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: L-Cit + HIIT
adolescents will be supplemented with 6 g/day of L-citrulline and 3 sessions per week of HIIT for 12 weeks
Dietary supplement: L-citrulline
oral supplementation of pure L-citrulline (6 g) for twelve weeks
Other: High Intensity Intervals Training
participants will have sessions 3 days a week for twelve weeks
Other Names:
  • HIIT
Active Comparator: L-Cit
adolescents will be supplemented with 6 g/day of L-citrulline but without do exercise for 12 weeks
Dietary supplement: L-citrulline
oral supplementation of pure L-citrulline (6 g) for twelve weeks
Placebo Comparator: Placebo + HIIT
adolescents will be supplemented with 6 g/day of Carboxymethyl cellulose and 3 sessions per week of HIIT for 12 weeks
Other: High Intensity Intervals Training
participants will have sessions 3 days a week for twelve weeks
Other Names:
  • HIIT
Dietary supplement: Carboxymethyl cellulose
oral supplementation of Carboxymethyl cellulose (6 g) as a placebo, for twelve weeks
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Arterial Stiffness
Time Frame: 12 weeks
The degree of arterial stiffness will be evaluated by oscillometric device (Mobil-O Graph). This device assesses Pulse Wave Velocity
12 weeks
Reflected Wave
Time Frame: 12 weeks
The Augmentation Index (AIx) measures the percentage of the pressure increase that is caused by the premature arrival of the reflected wave and is expressed as the ratio of PAo and PP multiplied by 100. AIx@75 is AIx corrected to a heart rate of 75 beats per minute. The Mobil-O Graph device also evaluates AIx@75
12 weeks
Degree of hepatic steatosis
Time Frame: 12 weeks

The degree of hepatic steatosis will be evaluated by abdominal ultrasound. It will be diagnosed as:

  1. Moderate, when sound attenuation is added.
  2. Severe, when the wall of the portal vessels and the diaphragm are not visible.
12 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Glucose metabolism: glucose
Time Frame: 12 weeks
Glucose will be evaluated by the Lakeside glucose oxidase method (GOD-PAPTM).
12 weeks
Glycated hemoglobin (HbA1c)
Time Frame: 12 weeks
Glycated hemoglobin (HbA1c) will be measured by reflectance spectrophotometry, by boronic acid affinity.
12 weeks
Insuline Resistance
Time Frame: 12 weeks
Insulin level will be measured by ELISA (ALPCO) method. The Homeostatic Model Assessment Index (HOMA-IR) will be calculated to determine insulin resistance.
12 weeks
Lipid profile
Time Frame: 12 weeks
The lipid profile will be measured by the modified Huang method.
12 weeks
VO2max
Time Frame: 12 weeks
VO2max is a measure of aerobic exercise capacity. It will be performed on a cycloergometer. Every 2 minutes 0.5 kp will be increased and HR will be measured minute by minute with a portable monitor (Polar HO1). When the participant no longer maintains the 60 rpm cadence or reaches the maximum perceived exertion on the modified Borg scale (9 or 10), the test is terminated.
12 weeks
Arterial Pressure
Time Frame: 12 weeks
Is pressure exerted by the blood on the artery wall. The mobil-O Graph also evaluates arterial pressure and reports it as Dyastolic Pressure (DAP), Systolic Pressure (SAP) and Mean Arterial Pressure (MAP)
12 weeks
Body composition
Time Frame: 12 weeks

Bioelectrical impedance will be used to assess total body composition as fat free mass (FFM), fat mass (FM) and total body water, using the standard configuration.

The portable, multi-frequency In body S10 device will be used and it reports body composition in percentage (%)
12 weeks

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Universidad de Guanajuato

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ma. Eugenia Garay-Sevilla, PhD, Universidad de Guanajuato
  • Study Chair: Alan Arturo Rodriguez-Carrillo, Bachelor, Universidad de Guanajuato

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 (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 14, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 15, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 30, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 19, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 18, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 21, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 16, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PWV-MAFLD-HIIT-CITRULLINE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

At the request of the researcher

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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.

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