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

April 15, 2026 updated by: Dulce González Islas, PhD, Instituto Nacional de Enfermedades Respiratorias

Effect of a Non-pharmacological Intervention (Nutritional Therapy and Pulmonary Rehabilitation) on Endothelial Function, Body Composition, and Physical Functionality in Recovered COVID-19 Patients.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2, represents a global public health crisis that has resulted in severe complications and death in more than 500,000 individuals worldwide.

The risk factors for severe COVID-19 include age over 70 years, hypertension, diabetes mellitus, smoking, coronary artery disease, and obesity, which have been associated with endothelial dysfunction (ED). The coexistence of chronic non-communicable diseases significantly exacerbates the inflammatory response, increasing the risk of adverse events and poor prognosis. Similarly, a high probability of cardiovascular diseases in subjects is at elevated risk of severe COVID-19, due to the overexpression of angiotensin-converting enzyme 2. In addition, in our country, the leading causes of death are related to metabolic diseases: 19% of men and women between the ages of 30 and 69 die from cardiovascular diseases, with diabetes ranking as the second leading cause of death. Furthermore, 76.6% of the population is overweight or obese, and 25.5% has hypertension, factors that render our population particularly susceptible to moderate to severe COVID-19.

Moreover, both pharmacological and non-pharmacological treatments have primarily focused on the acute phase of infection. However, it is essential to implement treatment protocols, including pulmonary rehabilitation and nutritional therapy with citrulline supplementation or immunonutrients with anti-inflammatory properties, to prevent Post-Intensive Care Syndrome, reduce systemic inflammation, and improve endothelial function. These interventions may collectively enhance protein synthesis, attenuate muscle mass loss, and promote patient autonomy, functional recovery, and overall quality of life.

Post-COVID-19 syndrome Post-COVID-19 syndrome has been defined as the persistence of symptoms and/or delayed long-term remission of complications arising from SARS-CoV-2 infection, occurring beyond 4 weeks after initial symptom onset.

Nutritional supplementation L-citrulline L-Citrulline is a non-essential, water-soluble alpha-amino acid and a potent endogenous precursor of L-arginine, which increases the bioavailability of NO. In endothelial cells, NO is synthesized from L-arginine by endothelial nitric oxide synthase, yielding NO and L-citrulline.

Endothelial dysfunction ED is a systemic condition in which the endothelium loses its physiological properties, including vascular permeability, vascular tone regulation, and neutrophil recruitment, thereby promoting a prothrombotic, proinflammatory, and pro-oxidant state.

General objective:

To evaluate the impact of a non-pharmacological intervention (nutritional therapy and pulmonary rehabilitation) on endothelial function, body composition, and physical functionality in recovered COVID-19 patients.

Specific objectives:

To evaluate the impact of a non-pharmacological intervention (nutritional therapy and pulmonary rehabilitation) on endothelial function in recovered COVID-19 patients.

To evaluate the impact of a non-pharmacological intervention (nutritional therapy and pulmonary rehabilitation) on body composition in recovered COVID-19 patients.

To evaluate the impact of a non-pharmacological intervention (nutritional therapy and pulmonary rehabilitation) on physical functionality in recovered COVID-19 patients.

To evaluate the impact of a non-pharmacological intervention (nutritional therapy and pulmonary rehabilitation) on quality of life in recovered COVID-19 patients.

Secondary objectives:

To describe the prevalence of sarcopenia in recovered COVID-19 patients. To describe cardiovascular alterations in recovered COVID-19 patients. To describe alterations in body composition in recovered COVID-19 patients. To describe metabolic alterations in recovered COVID-19 patients. To evaluate the effect of a non-pharmacological intervention (nutritional therapy and pulmonary rehabilitation) on muscle strength in recovered COVID-19 patients.

To evaluate the effect of a non-pharmacological intervention (nutritional therapy and pulmonary rehabilitation) on pulmonary function in recovered COVID-19 patients.

Study Type

Interventional

Enrollment (Actual)

43

Phase

  • 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
      • Mexico City, Mexico
        • Instituto Nacional De Enfermedades Respiratorias

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

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

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: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention group.
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
Subjects allocated to the intervention group receive 4 grams of L-citrulline supplementation daily, combined with nutritional therapy, over a 3-month period.
No Intervention: Control group.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Endothelial disfunction markers
Time Frame: 3 months

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
Time Frame: 3 months
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
Time Frame: 3 months

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

Collaborators and Investigators

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

Sponsor

Instituto Nacional de Enfermedades Respiratorias

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

November 9, 2020

Primary Completion (Actual)

November 11, 2022

Study Completion (Actual)

August 10, 2023

Study Registration Dates

First Submitted

April 7, 2026

First Submitted That Met QC Criteria

April 15, 2026

First Posted (Actual)

April 22, 2026

Study Record Updates

Last Update Posted (Actual)

April 22, 2026

Last Update Submitted That Met QC Criteria

April 15, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C71-20

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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