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

NCT05778266 | Completed DMC

• 1 other identifier: PWV-MAFLD-HIIT-CITRULLINE
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Metabolic Dysfunction-Associated Fatty Liver Disease; Obesity, Adolescent; Arterial Stiffness

Keywords

MAFLD; Obesity; Adolescents; PWV; AIx75; HIIT; L-citrulline supplementation

Outcome Measures

Primary Outcomes (3)

• Arterial Stiffness

  The degree of arterial stiffness will be evaluated by oscillometric device (Mobil-O Graph). This device assesses Pulse Wave Velocity

  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

  12 weeks

• Degree of hepatic steatosis

  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 Outcomes (7)

• Glucose metabolism: glucose

  12 weeks

• Glycated hemoglobin (HbA1c)

  12 weeks

• Insuline Resistance

  12 weeks

• Lipid profile

  12 weeks

• VO2max

  12 weeks

Study Arms (3)

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

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

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

Dietary Supplement: Carboxymethyl cellulose; Other: High Intensity Intervals Training

Interventions

L-citrulline DIETARY_SUPPLEMENT

oral supplementation of pure L-citrulline (6 g) for twelve weeks

L-Cit; L-Cit + HIIT

Carboxymethyl cellulose DIETARY_SUPPLEMENT

oral supplementation of Carboxymethyl cellulose (6 g) as a placebo, for twelve weeks

Also known as: Placebo

Placebo + HIIT

High Intensity Intervals Training OTHER

participants will have sessions 3 days a week for twelve weeks

Also known as: HIIT

L-Cit + HIIT; Placebo + HIIT

Eligibility Criteria

• Age: 15 Years - 19 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Universidad de Guanajuato: lead

Study Sites (1)

Universidad de Guanajuato

León, Guanajuato, 37000, Mexico

Location

Related Publications (1)

• 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.

  PMID: 39940261 DERIVED

MeSH Terms

Conditions

Pediatric Obesity; Obesity

Interventions

Citrulline; Carboxymethylcellulose Sodium

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amino Acids, Diamino; Amino Acids; Amino Acids, Peptides, and Proteins; Methylcellulose; Cellulose; Glucans; Polysaccharides; Carbohydrates

Study Officials

• Ma. Eugenia Garay-Sevilla, PhD

  Universidad de Guanajuato

  PRINCIPAL INVESTIGATOR

• Alan Arturo Rodriguez-Carrillo, Bachelor

  Universidad de Guanajuato

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The selection of which group each adolescent will belong to, will be made by randomization by computer numbers by a researcher from the department of medical sciences of the University of Guanajuato, who is not involved in treatment and follow-up. The researcher will designated into a placebo or L-cit group. The investigator and the participants will not know the group which they belong.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Titular Research Professor

Model Details: 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.

Study Record Dates

• First Submitted: February 19, 2023
• First Posted: March 21, 2023
• Study Start: March 14, 2023
• Primary Completion: January 15, 2024
• Study Completion: April 30, 2024
• Last Updated: December 20, 2024

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)