Arginine Replacement Therapy in COVID-19 (ART-COVID19)

April 10, 2026 updated by: Claudia R. Morris, Emory University

Prospective Open-Label Pilot Study of Arginine Replacement Therapy in Children Hospitalized With COVID-19

This study aims to investigate if receiving doses of arginine (a protein in the body) will improve mitochondria function in children with COVID-19.

The study will be performed at the Children's Healthcare of Atlanta, Arthur M. Blank Hospital. Patients will be randomized to receive one of three doses of arginine three times a day for five days or at discharge whichever comes first.

Study Overview

Status

Status

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

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

In the early stages of COVID-19, it was believed that children were immune or had very mild disease. Given the unfolding pandemic, children's cases are exhibiting an increasing global trend and are associated with some serious complications in addition to more long-term complications such as multisystem inflammatory syndrome in children (MIS-C) and "Long Covid". A significant number of hospitalized and critically ill pediatric patients have now been documented, in addition to a high number of emergency department (ED) visits despite previous reports suggesting rare or mild disease in children. The research team and others have shown that severe COVID-19 and MIS-C are associated with acute arginine deficiency in both adults and children. There has been increased evidence of the role of the endothelium associated with severe inflammation in COVID-19. Low plasma arginine bioavailability has been implicated in endothelial dysfunction, immune regulation, and hypercoagulation. The research team also identified high sPLA2 levels in COVID-19 and MIS-C, an observation previously made in children with Kawasaki's Disease. Subsequent studies have shown that sPLA2 is associated with the pathobiology leading to COVID-19 mortality, with enzyme levels 10-fold higher in people who died vs. mild disease and is also associated with Mito dysfunction. Not only could sPLA2 represent a prognostic indicator of disease severity, but it also represents a mechanism with potential therapeutic targets.

Information learned from the Mito activity in COVID-19 can contribute to further understanding of severe acute respiratory syndrome by coronavirus (SARS-CoV-2) infection. This data may help guide future treatment targets and strategies.

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 (Estimated)

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.
21

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.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Children's Healthcare of Atlanta (CHOA), Arthur M. Blank
        • Principal Investigator:
          • Caludia R Morris, MD
        • Contact:

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

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Established diagnosis of COVID-19 requiring admission to the hospital for treatment of COVID-19 infection
  • Age 3 years - 21 years of age

Exclusion Criteria:

  • Severe hepatic dysfunction: ALT> 6 x Upper limit of normal
  • Renal dysfunction: Creatinine > 1.5 x upper limit of normal or on dialysis
  • Acute Stroke
  • Pregnancy
  • Allergy to arginine
  • Past history of severe cardiac disease or significant cardiac surgery [minor procedures like ventricular septal defect (VSD) repair are not an exclusion]
  • History of significant pulmonary disease [Cystic Fibrosis, sickle cell disease (SCD)]
  • History of organ transplant
  • History of metabolic or mitochondrial disease (including Diabetes)
  • History of severe neurocognitive delays (severe cerebral palsy, anoxic brain injury)
  • History of ventriculoperitoneal (VP) shunt or hydrocephalus
  • PI discretion that the patient is not an ideal candidate for the study
  • History of HIV of immune compromise

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

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-arginine loading dose + standard dose
L-arginine loading dose (200 mg/kg IV) + standard dose (100 mg/kg IV TID).
Drug: Arginine Hydrochloride
Arginine will be infused based on the manufacturer's instructions (R-Gene 10, Pfizer), over 30 minutes. However, rates may be slowed to over 60 minutes for patients experiencing symptoms of flushing, nausea, vomiting, or headache at the research team's discretion. Pediatric doses will be drawn up by the pharmacy.
Other Names:
  • L-arginine
Active Comparator: Standard dose
Standard dose (100mg/kg IV TID).
Drug: Arginine Hydrochloride
Arginine will be infused based on the manufacturer's instructions (R-Gene 10, Pfizer), over 30 minutes. However, rates may be slowed to over 60 minutes for patients experiencing symptoms of flushing, nausea, vomiting, or headache at the research team's discretion. Pediatric doses will be drawn up by the pharmacy.
Other Names:
  • L-arginine
Active Comparator: Low dose
Low dose (25mg/kg IV TID).
Drug: Arginine Hydrochloride
Arginine will be infused based on the manufacturer's instructions (R-Gene 10, Pfizer), over 30 minutes. However, rates may be slowed to over 60 minutes for patients experiencing symptoms of flushing, nausea, vomiting, or headache at the research team's discretion. Pediatric doses will be drawn up by the pharmacy.
Other Names:
  • L-arginine

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
Change in mitochondrial function
Time Frame: Baseline and day 5
Complex-IV activity changes will be measured to estimate mitochondrial function before and after administration for L-arginine
Baseline and day 5

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
Change in amino acids
Time Frame: Baseline and day 5
arginine (ARG) ornithine (ORN) and citrulline (CIT) will be measured before and after administration for L-arginine
Baseline and day 5
Change in the arginase-1 activity/concentration
Time Frame: Baseline and day 5
arginase-1 will be measured before and after administration for L-arginine
Baseline and day 5
Change in myeloid-derived suppressor cells (MDSC-source of arginase-1)
Time Frame: Baseline and day 5
Myeloid-derived suppressor cells (MDSC) producing arginase-1 will be measured in the peripheral blood before and after administration of L-arginine
Baseline and day 5
Change in the level of cytokines (IL-6)
Time Frame: Baseline and day 5
Cytokines are biomarkers for inflammation. Cell supernatants will be collected and analyzed for different cytokines.
Baseline and day 5
Change on secretory phospholipase (sPLA2).
Time Frame: Baseline and day 5
Serum activity of secretory phospholipase (sPLA2) will be measured before and after administration for L-arginine
Baseline and day 5

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.
Emory University

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: Claudia R. Morris, MD, Emory University

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.
January 8, 2024

Primary Completion (Estimated)

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.
June 1, 2028

Study Completion (Estimated)

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.
June 1, 2028

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).
May 9, 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.
May 9, 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.
May 11, 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.
April 15, 2026

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.
April 10, 2026

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.
April 1, 2026

More Information

Terms related to this study

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.
  • STUDY00005572
  • 2025P010543 (Other Identifier: Emory Insight Humans IRB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Upon request, the research team will share de-identified data with researchers who provide a methodologically sound proposal.

IPD Sharing Time Frame

Data are available for at least 5 years after publication of primary results.

IPD Sharing Access Criteria

Data are available for at least 5 years, available upon request from PI, directed to claudia.r.morris@emory.edu

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

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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