Effect of a Non-pharmacological Intervention on Endothelial Function, Body Composition, and Physical Functionality in Recovered COVID-19 Patients.

NCT07544186 | Completed

• 1 other identifier: C71-20
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the impact of a non-pharmacological treatment (nutritional therapy and pulmonary rehabilitation) on endothelial function, body composition, and physical functionality in recovered COVID-19 patients. The primary research question is: What is the effect of a non-pharmacological treatment (nutritional therapy and pulmonary rehabilitation) on endothelial function, body composition, and physical capacity in recovered COVID-19 patients, compared to those receiving conventional medical management? A nutritional treatment combined with L-citrulline supplementation (intervention group) will be compared against conventional treatment alone (control group). Both groups will undergo pulmonary rehabilitation for a 3-month follow-up. Subjects assigned to the intervention group will be required to:

• Take 4 g of L-citrulline daily for 3 months.
• Attend an interim session at 1.5 months for review of the nutritional treatment and supplementation.
• Keep a record of each supplement intake.

Conditions

Supplemental Nutrition Assistance Program Education; Post COVID Syndrome; Endothelial Function

Keywords

Post-COVID-19 syndrome; Endothelial function; Body composition; L-citrulline; Physical functionality

Outcome Measures

Primary Outcomes (3)

• Endothelial disfunction markers

  E-Selectin, ng/ml was Serum nitric oxide concentration was assessed indirectly through the enzymatic conversion of nitrate to nitrite (pg/ml). sE-Selectin (ng/ml) and Endothelin-1 (ng/ml) levels were measured using a human enzyme-linked immunosorbent assay (ELISA) kit (R\&D Systems, Inc., Minneapolis, MN, USA). ICAM-1 (ng/mg of protein )and VCAM-1 (ng/mg of protein) was assessed using a method is the sandwich enzyme-linked immunosorbent assay (ELISA).

  3 months

• Body composition

  Body composition was measured using whole-body electrical bioimpedance with RJL Systems Quantum single-frequency. Weight was expressed in kilograms, fat-mass in percentage, phase angle in grades, and the appendicular skeletal muscle mass index in kg/m2.

  3 months

• Physical functionality

  Handgrip strength was measured using a mechanical Smedley Hand Dynamometer, this outcome measure was expressed in kilograms. Exercise tolerance was evaluated using a six-minute walk test, the distance covered was expressed in meters. Pulmonary rehabilitation: static and dynamic balance, gait, fall risk, cognitive function, peripheral strength assessed by manual muscle testing, quality of life, anxiety and depression screening, and perceived disability. The results were presented in scores obtained for each test.

  3 months

Study Arms (2)

Intervention group.

EXPERIMENTAL

Intervention group: Subjects will receive conventional medical and nutritional treatment supplemented with 4 g/day L-citrulline supplementation for 3 months, as well as a home-based PR program prescribed by a rehabilitation physician according to each patient's individual needs and physical capacity, specifically for those whose clinical condition does not require attending in-person PR sessions three times per week at INER. Assessments will be conducted at baseline and 3 months.

Dietary Supplement: L-citrulline supplementation

Control group.

NO INTERVENTION

Control group: Subjects will receive conventional medical and nutritional treatment, as well as a home-based pulmonary rehabilitation (PR) program prescribed by a rehabilitation physician according to each patient's individual needs and physical capacity, specifically for those whose clinical condition does not require attending in-person PR sessions three times per week at INER. Assessments will be conducted at baseline, and 3 months.

Interventions

L-citrulline supplementation DIETARY_SUPPLEMENT

Subjects allocated to the intervention group receive 4 grams of L-citrulline supplementation daily, combined with nutritional therapy, over a 3-month period.

Intervention group.

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Recovered COVID-19 patients with a negative PCR test for SARS-CoV-2.
• Subjects between 40 and 80 years.
• Subjects who give written informed consent to participate in the study.

You may not qualify if:

• Subjects diagnosed with Human Immunodeficiency Virus (HIV).
• Subjects diagnosed with cancer.
• Subjects with a glomerular filtration rate (GFR) \<30 ml/min/1.73 m².
• Subjects currently enrolled in another interventional study.

Sponsors & Collaborators

• Instituto Nacional de Enfermedades Respiratorias: lead

Study Sites (1)

Instituto Nacional de Enfermedades Respiratorias

Mexico City, Mexico

Location

Related Publications (7)

• Nalbandian A, Sehgal K, Gupta A, Madhavan MV, McGroder C, Stevens JS, Cook JR, Nordvig AS, Shalev D, Sehrawat TS, Ahluwalia N, Bikdeli B, Dietz D, Der-Nigoghossian C, Liyanage-Don N, Rosner GF, Bernstein EJ, Mohan S, Beckley AA, Seres DS, Choueiri TK, Uriel N, Ausiello JC, Accili D, Freedberg DE, Baldwin M, Schwartz A, Brodie D, Garcia CK, Elkind MSV, Connors JM, Bilezikian JP, Landry DW, Wan EY. Post-acute COVID-19 syndrome. Nat Med. 2021 Apr;27(4):601-615. doi: 10.1038/s41591-021-01283-z. Epub 2021 Mar 22.

  PMID: 33753937 BACKGROUND

• Huertas A, Montani D, Savale L, Pichon J, Tu L, Parent F, Guignabert C, Humbert M. Endothelial cell dysfunction: a major player in SARS-CoV-2 infection (COVID-19)? Eur Respir J. 2020 Jul 30;56(1):2001634. doi: 10.1183/13993003.01634-2020. Print 2020 Jul.

  PMID: 32554538 BACKGROUND

• Allerton TD, Proctor DN, Stephens JM, Dugas TR, Spielmann G, Irving BA. l-Citrulline Supplementation: Impact on Cardiometabolic Health. Nutrients. 2018 Jul 19;10(7):921. doi: 10.3390/nu10070921.

  PMID: 30029482 BACKGROUND

• Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11.

  PMID: 32171076 BACKGROUND

• Chen L, Hao G. The role of angiotensin-converting enzyme 2 in coronaviruses/influenza viruses and cardiovascular disease. Cardiovasc Res. 2020 Oct 1;116(12):1932-1936. doi: 10.1093/cvr/cvaa093.

  PMID: 32267499 BACKGROUND

• Del Turco S, Vianello A, Ragusa R, Caselli C, Basta G. COVID-19 and cardiovascular consequences: Is the endothelial dysfunction the hardest challenge? Thromb Res. 2020 Dec;196:143-151. doi: 10.1016/j.thromres.2020.08.039. Epub 2020 Aug 27.

  PMID: 32871306 BACKGROUND

• Instituto Nacional de Estadística y Geografía. Nota técnica: Estadística de Defunciones Registradas 2020 [Internet]. Aguascalientes: INEGI; 2021 Disponible en: https://www.inegi.org.mx/contenidos/programas/edr/doc/defunciones_registradas_2020_nota_tecnica.pdf

  BACKGROUND

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: An open-label, randomized controlled clinical trial was conducted.

Study Record Dates

• First Submitted: April 7, 2026
• First Posted: April 22, 2026
• Study Start: November 9, 2020
• Primary Completion: November 11, 2022
• Study Completion: August 10, 2023
• Last Updated: April 22, 2026

Record last verified: 2026-04

Locations

ME (1)