Arginine Therapy for COVID-19

(ART-COVID19 Trial)

Recruiting at 1 trial location

Overseen By Dunia Hatabah, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Disqualifiers: Severe hepatic dysfunction, Renal dysfunction, Acute stroke, Pregnancy, Allergy to arginine, Severe cardiac disease, Significant pulmonary disease, Organ transplant, Metabolic or mitochondrial disease, Severe neurocognitive delays, VP shunt or hydrocephalus, HIV or immune compromise, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5 days

21 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study team for guidance.

How does the drug Arginine Hydrochloride differ from other COVID-19 treatments?

Arginine Hydrochloride (L-arginine) is unique because it is an amino acid that may help improve blood flow and immune function, which could be beneficial in treating COVID-19. Unlike other treatments that directly target the virus or inflammation, L-arginine may support the body's natural processes to fight the infection. ^{1 2 3 4 5}

Who Is on the Research Team?

Claudia Morris, MD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 3 to 21 who are hospitalized with COVID-19. They must not have severe heart issues, kidney dysfunction, liver problems, metabolic diseases like diabetes, or compromised immune systems. Pregnant individuals or those with allergies to arginine can't participate.

Inclusion Criteria

I am between 3 and 21 years old.

I am hospitalized due to COVID-19.

Exclusion Criteria

I have a history of HIV or a weakened immune system.

My kidney function is impaired, with creatinine levels above normal or I am on dialysis.

I have had an organ transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive one of three doses of arginine three times a day for five days or until discharge

5 days

Daily visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Arginine Hydrochloride

Trial Overview The study tests if different doses of arginine hydrochloride given three times daily can improve mitochondrial function in pediatric patients with COVID-19. The treatment lasts five days or until discharge.

How Is the Trial Designed?

Group I: L-arginine loading dose + standard dose Active Control 1 Intervention

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

Group II: Standard dose Active Control 1 Intervention

Standard dose (100mg/kg IV TID).

Group III: Low dose Active Control 1 Intervention

Low dose (25mg/kg IV TID).

Arginine Hydrochloride is already approved in European Union, United States for the following indications:

Approved in European Union as L-arginine for:

• Nutritional supplement
• COVID-19-related conditions

Approved in United States as L-arginine for:

• Nutritional supplement
• COVID-19-related conditions

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Published Research Related to This Trial

In a study involving 14 patients with stable angina, the administration of oral L-arginine during continuous transdermal nitroglycerin (TD-GTN) therapy significantly improved treadmill walking time, indicating enhanced exercise performance compared to placebo.

L-arginine appears to modify or prevent the development of nitrate tolerance associated with TD-GTN therapy, suggesting it may help maintain the efficacy of nitroglycerin treatment over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of supplemental L-arginine on tolerance development during continuous transdermal nitroglycerin therapy. Parker, JO., Parker, JD., Caldwell, RW., et al.[2019]

In a phase 2 clinical trial involving 96 patients with non-small cell lung cancer and brain metastases, the combination of transdermal nitroglycerin (NTG) and whole brain radiation therapy (WBRT) significantly improved the intracranial objective response rate (iORR) compared to WBRT alone, with a response rate of 56.5% in the NTG group versus 32.7% in the control group.

Patients receiving NTG plus WBRT also experienced a longer intracranial progression-free survival (ICPFS) of 27.7 months compared to 9.6 months for those receiving WBRT alone, particularly benefiting those with epidermal growth factor receptor mutations (EGFRm). However, the NTG group reported a higher incidence of vomiting as a side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitroglycerin Plus Whole Intracranial Radiation Therapy for Brain Metastases in Patients With Non-Small Cell Lung Cancer: A Randomized, Open-Label, Phase 2 Clinical Trial. Arrieta, O., Hernández-Pedro, N., Maldonado, F., et al.[2023]

Nitroglycerin (NTG) is a prodrug that releases nitric oxide (NO), which has both potential tumor-promoting and tumor-fighting effects, making it a candidate for enhancing cancer treatments.

NTG has been studied in various preclinical and clinical settings as a NO-releasing agent to combat cancer therapeutic resistance, suggesting it could improve standard cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitroglycerin: a comprehensive review in cancer therapy. Meunier, M., Yammine, A., Bettaieb, A., et al.[2023]

In a randomized phase II trial involving 223 patients with stage IV nonsquamous NSCLC, adding nitroglycerin (NTG) to the standard treatment of carboplatin, paclitaxel, and bevacizumab did not improve progression-free survival (PFS) or overall survival (OS).

While the addition of NTG did not enhance treatment outcomes, it was associated with a higher incidence of headaches (52% in the NTG group), indicating a potential side effect without therapeutic benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase II study comparing paclitaxel-carboplatin-bevacizumab with or without nitroglycerin patches in patients with stage IV nonsquamous nonsmall-cell lung cancer: NVALT12 (NCT01171170)†. Dingemans, AM., Groen, HJ., Herder, GJ., et al.[2020]

Nitroglycerin, used since 1847 for treating angina pectoris, works through both nitric oxide-dependent and independent mechanisms to promote vasodilation and improve blood flow, making it effective for cardiovascular diseases.

A significant limitation of nitroglycerin therapy is the development of tolerance, which can be managed by implementing a dosing strategy that includes periods of no or low nitrate exposure within a 24-hour cycle.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Nitroglycerin and Other Nitrogen Oxides in Cardiovascular Therapeutics. Divakaran, S., Loscalzo, J.[2022]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

The effect of supplemental L-arginine on tolerance development during continuous transdermal nitroglycerin therapy. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Nitroglycerin Plus Whole Intracranial Radiation Therapy for Brain Metastases in Patients With Non-Small Cell Lung Cancer: A Randomized, Open-Label, Phase 2 Clinical Trial. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Nitroglycerin: a comprehensive review in cancer therapy. [2023]

4. England pubmed.ncbi.nlm.nih.gov

A randomized phase II study comparing paclitaxel-carboplatin-bevacizumab with or without nitroglycerin patches in patients with stage IV nonsquamous nonsmall-cell lung cancer: NVALT12 (NCT01171170)†. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

The Role of Nitroglycerin and Other Nitrogen Oxides in Cardiovascular Therapeutics. [2022]