Arginine Replacement Therapy in COVID-19

NCT ID: NCT05855330

Last Updated: 2025-04-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-08
• Study Completion Date: 2027-06-30

Brief 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. 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.

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

L-arginine loading dose + standard dose

L-arginine loading dose (200 mg/kg IV) + standard dose (100 mg/kg IV TID).

Group Type: ACTIVE_COMPARATOR

Arginine Hydrochloride

Intervention Type: DRUG

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.

Standard dose

Standard dose (100mg/kg IV TID).

Group Type: ACTIVE_COMPARATOR

Arginine Hydrochloride

Intervention Type: DRUG

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.

Low dose

Low dose (25mg/kg IV TID).

Group Type: ACTIVE_COMPARATOR

Arginine Hydrochloride

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

L-arginine

Eligibility Criteria

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

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Claudia R. Morris

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Claudia R. Morris, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Children's Healthcare of Atlanta (CHOA), Arthur M. Blank

Atlanta, Georgia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Claudia R. Morris, MD

Role: CONTACT

claudia.r.morris@emory.edu

404 727-5500

Dunia Hatabah, MD

Role: CONTACT

dunia.hatabah@emory.edu

470-6626706

Facility Contacts

Claudia R Morris, MD

Role: primary

claudia.morris@choa.org

404 727-5500

Other Identifiers

STUDY00005572

Identifier Type: -

Identifier Source: org_study_id