Metabolic Dysfunction-Associated Fatty Liver DiseaseNCT05778266
Effect of L-citrulline and HIIT on Arterial Stiffness, Body Composition, and Lipid Profile in Adolescents with Steatosis Associated with Metabolic Dysfunction (MASLD)
A study testing L-citrulline, Carboxymethyl cellulose and High Intensity Intervals Training in people with Metabolic Dysfunction-Associated Fatty Liver Disease and Obesity, Adolescent, run by Universidad de Guanajuato at 1 site in Mexico.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 15 to 19 years
- Conditions the study is for
- Metabolic Dysfunction-Associated Fatty Liver Disease, Obesity, Adolescent, Arterial Stiffness
- What is being tested?
- L-citrulline, Carboxymethyl cellulose and High Intensity Intervals Training
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 43 participants
- Where
- 1 siteMexico
- Study dates
- 14 Mar 2023to 30 Apr 2024
- 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 15 to 19 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Metabolic Dysfunction-Associated Fatty Liver Disease, Obesity, Adolescent, Arterial Stiffness
- Being tested
- L-citrulline, Carboxymethyl cellulose, High Intensity Intervals Training
- Keywords
- MAFLD, Obesity, Adolescents, PWV, AIx75, HIIT, L-citrulline supplementation
- Medical subject headings
- Pediatric Obesity, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-citrullineDietary supplement
oral supplementation of pure L-citrulline (6 g) for twelve weeks
Carboxymethyl celluloseDietary supplement
Also called Placebo
oral supplementation of Carboxymethyl cellulose (6 g) as a placebo, for twelve weeks
High Intensity Intervals TrainingOther
Also called HIIT
participants will have sessions 3 days a week for twelve weeks
| Study group | Role | What they receive |
|---|---|---|
| L-Cit + HIIT | Active comparator | adolescents will be supplemented with 6 g/day of L-citrulline and 3 sessions per week of HIIT for 12 weeks Receives: Dietary Supplement: L-citrulline; Other: High Intensity Intervals Training |
| L-Cit | Active comparator | adolescents will be supplemented with 6 g/day of L-citrulline but without do exercise for 12 weeks Receives: Dietary Supplement: L-citrulline |
| Placebo + HIIT | Placebo comparator | adolescents will be supplemented with 6 g/day of Carboxymethyl cellulose and 3 sessions per week of HIIT for 12 weeks Receives: Dietary Supplement: Carboxymethyl cellulose; Other: High Intensity Intervals Training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Arterial Stiffness
The degree of arterial stiffness will be evaluated by oscillometric device (Mobil-O Graph). This device assesses Pulse Wave Velocity
Measured: 12 weeks
Reflected Wave
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
Measured: 12 weeks
Degree of hepatic steatosis
The degree of hepatic steatosis will be evaluated by abdominal ultrasound. It will be diagnosed as:
- Moderate, when sound attenuation is added.
- Severe, when the wall of the portal vessels and the diaphragm are not visible.
Measured: 12 weeks
Secondary outcomes (7)
Glucose metabolism: glucose
Glucose will be evaluated by the Lakeside glucose oxidase method (GOD-PAPTM).
Measured: 12 weeks
Glycated hemoglobin (HbA1c)
Glycated hemoglobin (HbA1c) will be measured by reflectance spectrophotometry, by boronic acid affinity.
Measured: 12 weeks
Insuline Resistance
Insulin level will be measured by ELISA (ALPCO) method. The Homeostatic Model Assessment Index (HOMA-IR) will be calculated to determine insulin resistance.
Measured: 12 weeks
Lipid profile
The lipid profile will be measured by the modified Huang method.
Measured: 12 weeks
VO2max
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.
Measured: 12 weeks
Arterial Pressure
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)
Measured: 12 weeks
Body composition
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 (%)
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2023
- Study start14 Mar 2023
- Primary completion15 Jan 2024
- Study completion30 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metabolic Dysfunction-Associated Fatty Liver DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Parallel groups
- Model description
- An intervention with exercise in modality of High-Intensity Interval Training (HIIT) and Oral administration of L-citrulline (L-cit) or placebo (Pl) as follows: Group L-cit + HIIT: capsules of 6 g of citrulline will be supplemented per day, distributed as 3 g (4 capsules) in the morning before the first meal and 3 g in the evening before sleep for a period of 12 weeks. The sessions of HIIT will be made 3 days per week in a stationary bicycle Group Pl + HIIT: Carboxymethyl cellulose will be used as placebo. 4 capsules will be taken in the morning before the first meal and 4 capsules at night before going to sleep for a period of 12 weeks. The sessions of HIIT will be made 3 days per week in a stationary bicycle. Group L-cit without HIIT: capsules of citrulline will be supplemented per day, distributed as 3 g (4 capsules) in the morning before the first meal and 3 g (4 capsules) in the evening before sleep for a period of 12 weeks. This group will not made exercise.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universidad de Guanajuato
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ma Eugenia Garay Sevilla, Universidad de Guanajuato
- Investigators
- Ma. Eugenia Garay-Sevilla, PhD, Principal investigator, Universidad de GuanajuatoAlan Arturo Rodriguez-Carrillo, Bachelor, Study chair, Universidad de Guanajuato
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05778266
- Sponsor's protocol ID
- PWV-MAFLD-HIIT-CITRULLINE
- Status last verified
- Mar 2023
- First submitted
- 19 Feb 2023
- Last updated
- 20 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: At the request of the researcher
Publications
Rodriguez-Carrillo AA, Espinoza-Vargas MR, Vargas-Ortiz K, Ibarra-Reynoso LDR, Olvera-Juarez M, Gomez-Ojeda A, Garay-Sevilla ME, Figueroa A. Impact of L-Citrulline Supplementation and HIIT on Lipid Profile, Arterial Stiffness, and Fat Mass in Obese Adolescents with Metabolic-Dysfunction-Associated Fatty Liver Disease: A Randomized Clinical Trial. Nutrients. 2025 Jan 23;17(3):402. doi: 10.3390/nu17030402.
PubMed 39940261
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of L-citrulline and HIIT on Arterial Stiffness, Body Composition, and Lipid Profile in Adolescents with Steatosis Associated with Metabolic Dysfunction (MASLD)
- ClinicalTrials.gov ID
- NCT05778266
- Acronym / sponsor ID
- PWV-MAFLD-HIIT-CITRULLINE
- Conditions
- Metabolic Dysfunction-Associated Fatty Liver Disease, Obesity, Adolescent, Arterial Stiffness
- Keywords
- MAFLD, Obesity, Adolescents, PWV, AIx75, HIIT, L-citrulline supplementation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Universidad de GuanajuatoUniversity, hospital or other
- Study start
- 14 Mar 2023 (actual)
- Primary completion
- 15 Jan 2024 (actual)
- Study completion
- 30 Apr 2024 (actual)
- First posted
- 21 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
- Model description
- An intervention with exercise in modality of High-Intensity Interval Training (HIIT) and Oral administration of L-citrulline (L-cit) or placebo (Pl) as follows: Group L-cit + HIIT: capsules of 6 g of citrulline will be supplemented per day, distributed as 3 g (4 capsules) in the morning before the first meal and 3 g in the evening before sleep for a period of 12 weeks. The sessions of HIIT will be made 3 days per week in a stationary bicycle Group Pl + HIIT: Carboxymethyl cellulose will be used as placebo. 4 capsules will be taken in the morning before the first meal and 4 capsules at night before going to sleep for a period of 12 weeks. The sessions of HIIT will be made 3 days per week in a stationary bicycle. Group L-cit without HIIT: capsules of citrulline will be supplemented per day, distributed as 3 g (4 capsules) in the morning before the first meal and 3 g (4 capsules) in the evening before sleep for a period of 12 weeks. This group will not made exercise.
| Arm | Type | Receives |
|---|---|---|
| L-Cit + HIIT | Active comparator | Dietary Supplement: L-citrulline, Other: High Intensity Intervals Trainingadolescents will be supplemented with 6 g/day of L-citrulline and 3 sessions per week of HIIT for 12 weeks |
| L-Cit | Active comparator | Dietary Supplement: L-citrullineadolescents will be supplemented with 6 g/day of L-citrulline but without do exercise for 12 weeks |
| Placebo + HIIT | Placebo comparator | Dietary Supplement: Carboxymethyl cellulose, Other: High Intensity Intervals Trainingadolescents will be supplemented with 6 g/day of Carboxymethyl cellulose and 3 sessions per week of HIIT for 12 weeks |
Who may qualify
- Ages
- 15 to 19 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L-citrullineoral supplementation of pure L-citrulline (6 g) for twelve weeks | Dietary supplement | L-Cit, L-Cit + HIIT |
| Carboxymethyl celluloseAlso: Placebooral supplementation of Carboxymethyl cellulose (6 g) as a placebo, for twelve weeks | Dietary supplement | Placebo + HIIT |
| High Intensity Intervals TrainingAlso: HIITparticipants will have sessions 3 days a week for twelve weeks | Other | L-Cit + HIIT, Placebo + HIIT |
Primary outcome
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
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
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.
7 secondary outcomes
Glucose metabolism: glucose
Time frame: 12 weeks
Glycated hemoglobin (HbA1c)
Time frame: 12 weeks
Insuline Resistance
Time frame: 12 weeks
Lipid profile
Time frame: 12 weeks
VO2max
Time frame: 12 weeks
Arterial Pressure
Time frame: 12 weeks
Body composition
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Dec 2024.
- Derived from this study: PubMed 39940261Rodriguez-Carrillo AA, Espinoza-Vargas MR, Vargas-Ortiz K, Ibarra-Reynoso LDR, Olvera-Juarez M, Gomez-Ojeda A, Garay-Sevilla ME, Figueroa A. Impact of L-Citrulline Supplementation and HIIT on Lipid Profile, Arterial Stiffness, and Fat Mass in Obese Adolescents with Metabolic-Dysfunction-Associated Fatty Liver Disease: A Randomized Clinical Trial. Nutrients. 2025 Jan 23;17(3):402. doi: 10.3390/nu17030402.
- Individual participant dataSharing planned: No. At the request of the researcher
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ma. Eugenia Garay-Sevilla, PhD principal investigator
Universidad de Guanajuato
Alan Arturo Rodriguez-Carrillo, Bachelor study chair
Universidad de Guanajuato
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing L-citrulline, Carboxymethyl cellulose and High Intensity Intervals Training in people with Metabolic Dysfunction-Associated Fatty Liver Disease and Obesity, Adolescent, run by Universidad de Guanajuato at 1 site in Mexico.
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 8 inclusion and 5 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: finished, as of the sponsor's last update on 20 Dec 2024. 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 Mexico. 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. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Arterial Stiffness (time frame: 12 weeks). The study lists 3 primary outcomes in all. 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 NCT05778266, which also lists 1 linked publication.
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 20 Dec 2024.