COVID-19Phase 2ART-COVID19NCT05855330
Arginine Replacement Therapy in COVID-19
A Phase 2 study testing Arginine Hydrochloride in people with COVID-19, run by Emory University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 3 to 21 years
- Conditions the study is for
- COVID-19
- What is being tested?
- Arginine Hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Jan 2024to Jun 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 3 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Established diagnosis of COVID-19 requiring admission to the hospital for treatment of COVID-19 infection
- Age 3 years - 21 years of age
Who cannot join
- 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]
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Children's Healthcare of Atlanta (CHOA), Arthur M. Blank
Atlanta, Georgia, 30322
Claudia R Morris, MD, 404 727-5500, claudia.morris@choa.org
Caludia R Morris, MD
About this study
Official title: 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.
Read the 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.
- Conditions
- COVID-19
- Being tested
- Arginine Hydrochloride
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arginine HydrochlorideDrug
Also called L-arginine
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.
| Study group | Role | What they receive |
|---|---|---|
| L-arginine loading dose + standard dose | Active comparator | L-arginine loading dose (200 mg/kg IV) + standard dose (100 mg/kg IV TID). Receives: Drug: Arginine Hydrochloride |
| Standard dose | Active comparator | Standard dose (100mg/kg IV TID). Receives: Drug: Arginine Hydrochloride |
| Low dose | Active comparator | Low dose (25mg/kg IV TID). Receives: Drug: Arginine Hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in mitochondrial function
Complex-IV activity changes will be measured to estimate mitochondrial function before and after administration for L-arginine
Measured: Baseline and day 5
Secondary outcomes (5)
Change in amino acids
arginine (ARG) ornithine (ORN) and citrulline (CIT) will be measured before and after administration for L-arginine
Measured: Baseline and day 5
Change in the arginase-1 activity/concentration
arginase-1 will be measured before and after administration for L-arginine
Measured: Baseline and day 5
Change in myeloid-derived suppressor cells (MDSC-source of arginase-1)
Myeloid-derived suppressor cells (MDSC) producing arginase-1 will be measured in the peripheral blood before and after administration of L-arginine
Measured: Baseline and day 5
Change in the level of cytokines (IL-6)
Cytokines are biomarkers for inflammation. Cell supernatants will be collected and analyzed for different cytokines.
Measured: Baseline and day 5
Change on secretory phospholipase (sPLA2).
Serum activity of secretory phospholipase (sPLA2) will be measured before and after administration for L-arginine
Measured: Baseline and day 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2023
- Study start8 Jan 2024
- Primary completionJun 2028 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Claudia R. Morris, Emory University
- Investigators
- Claudia R. Morris, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05855330
- Sponsor's protocol ID
- STUDY00005572
- Other IDs
- 2025P010543
- Acronym
- ART-COVID19
- Status last verified
- Apr 2026
- First submitted
- 9 May 2023
- Last updated
- 15 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Upon request, the research team will share de-identified data with researchers who provide a methodologically sound proposal.
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Open-Label Pilot Study of Arginine Replacement Therapy in Children Hospitalized With COVID-19
- ClinicalTrials.gov ID
- NCT05855330
- Acronym / sponsor ID
- ART-COVID19 / STUDY00005572
- Conditions
- COVID-19
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 21 participants (estimated)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Study start
- 8 Jan 2024 (actual)
- Primary completion
- Jun 2028 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 11 May 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.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| L-arginine loading dose + standard dose | Active comparator | Drug: Arginine HydrochlorideL-arginine loading dose (200 mg/kg IV) + standard dose (100 mg/kg IV TID). |
| Standard dose | Active comparator | Drug: Arginine HydrochlorideStandard dose (100mg/kg IV TID). |
| Low dose | Active comparator | Drug: Arginine HydrochlorideLow dose (25mg/kg IV TID). |
Who may qualify
- Ages
- 3 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- Established diagnosis of COVID-19 requiring admission to the hospital for treatment of COVID-19 infection
- Age 3 years - 21 years of age
Key exclusion criteria (13 listed)
- 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
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 |
|---|---|---|
| Arginine HydrochlorideAlso: L-arginineArginine 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. | Drug | L-arginine loading dose + standard dose, Low dose, Standard dose |
Primary outcome
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
5 secondary outcomes
Change in amino acids
Time frame: Baseline and day 5
Change in the arginase-1 activity/concentration
Time frame: Baseline and day 5
Change in myeloid-derived suppressor cells (MDSC-source of arginase-1)
Time frame: Baseline and day 5
Change in the level of cytokines (IL-6)
Time frame: Baseline and day 5
Change on secretory phospholipase (sPLA2).
Time frame: Baseline and day 5
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2026.
- Individual participant dataSharing planned: Yes. Upon request, the research team will share de-identified data with researchers who provide a methodologically sound proposal.
Related trials for COVID-19
Not yet recruitingPhase 1
Evaluating AVM0703 for Treatment of COVID-19 or Influenza-mediated ARDS
ARDS, Covid19
Active, not recruitingObservational study
Vaccine Responses to SARS-CoV-2 and Other Emerging Infectious Diseases
COVID-19, Vaccination
RecruitingPhase 4
Comparative Immunogenicity of Respiratory Virus Vaccines (CIRV2) Study
COVID -19, COVID - 19
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
RecruitingObservational study
Clinical Outcomes and Pharmacotherapy Effectiveness in the VA Health Care System (COPE-VA)
COVID-19, SARS-CoV-2 Infection, RSV
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.
Claudia R. Morris, MD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Arginine Hydrochloride in people with COVID-19, run by Emory University at 1 site in United States.
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 2 inclusion and 13 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: looking for participants now, as of the sponsor's last update on 15 Apr 2026. 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 United States. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Claudia R. Morris, MD (404 727-5500, claudia.r.morris@emory.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in mitochondrial function (time frame: Baseline and day 5). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Apr 2026.