S-Nitrosylation Therapy for COVID-19

Overseen By Robert Schilz, DO, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Robert Schilz

Must not be taking: Nitrates, PDE-5 inhibitors, others

Disqualifiers: Lung malignancy, Anemia, Pregnancy, others

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for severe COVID-19 using S-nitrosylation therapy (SNO Therapy). Researchers aim to determine if this treatment can aid patients with serious breathing issues caused by the virus. Participants will be divided into two groups: one receiving the experimental therapy and the other a placebo (an inactive treatment). Ideal candidates are those currently hospitalized with confirmed COVID-19, experiencing serious respiratory distress, and requiring more than 4 liters of oxygen per minute. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications. The trial excludes individuals taking nitrates, PDE-5 inhibitors, nitric oxide donors, drugs that increase methemoglobin, drugs that interfere with nitrite metabolism, and drugs that may cause low blood pressure.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that S-nitrosylation therapy, which uses nitric oxide, is under investigation as a treatment for severe COVID-19. Past studies on inhaled nitric oxide suggest it might improve breathing and oxygen levels in patients. However, results have been mixed, and further research is necessary to confirm these benefits.

In terms of safety, this treatment remains in the early testing stages, so limited information exists about its effects on people. Early trials focus on assessing safety and determining the appropriate dose. So far, no clear evidence of serious side effects has emerged, but additional studies are required to ensure safety. Prospective trial participants should consider this information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about S-nitrosylation therapy for COVID-19 because it introduces a novel mechanism of action that differentiates it from current treatments, like antivirals and monoclonal antibodies. While standard treatments target the virus directly or modulate the immune response, S-nitrosylation involves delivering SNO, a compound that can release nitric oxide to help regulate inflammation and improve blood flow. This could lead to more effective management of COVID-19 symptoms, potentially offering quicker relief and improved outcomes for patients.

What evidence suggests that S-nitrosylation therapy might be an effective treatment for COVID-19?

This trial will compare S-nitrosylation therapy with a placebo to evaluate its potential in treating COVID-19. Research suggests that S-nitrosylation therapy might help by affecting how the virus enters cells. One study found that S-nitrosylation targets the ACE2 receptor, which the virus uses to infect cells. This targeting could potentially stop the virus from spreading in the body. While the exact benefits are still under investigation, early results indicate this method might slow the virus. However, further research is needed to confirm these possible effects. ^{1 3 6 7 8}

Who Is on the Research Team?

Robert Schilz, DO, PhD

Principal Investigator

University Hospitals Cleveland Medical Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-89 with confirmed COVID-19, experiencing mild respiratory distress and needing more than 4 liters/min of oxygen but not on active ventilatory support. They must be able to consent or have a representative who can. Excluded are pregnant/breastfeeding individuals, those with certain heart/lung/kidney diseases, anemia, taking specific medications that could interact negatively, or at high risk of methemoglobin formation.

Inclusion Criteria

I am over 18 and can give or have someone to give consent for me.

I am hospitalized with COVID-19 confirmed by a test.

I can start ENO treatment after my oxygen levels are stable.

Exclusion Criteria

Individuals who are pregnant or breastfeeding

I am a COVID-19 patient using extra oxygen or a machine to help me breathe.

I have a blood disorder that affects clotting or oxygen delivery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a 6-hour escalating dose of S-nitrosylation therapy or placebo

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

What Are the Treatments Tested in This Trial?

Interventions

• Nitrogen gas
• SNO

Trial Overview The study tests S-nitrosylation therapy using SNO and nitrogen gas in treating severe acute respiratory syndrome coronavirus (SARS-CoV2) infection. It aims to see if this treatment can help patients breathe better without the need for more intensive breathing support like ventilators.

How Is the Trial Designed?

Group I: SNO Experimental Treatment 1 Intervention

12 patients in the S-nitrosylation arm will receive SNO (six-hour treatment with a sequential increasing dose regimen of 20 ppm x 2 hr, 40 ppm x 2 hr, 80 ppm x 2 hr).

Group II: Placebo Placebo Group 1 Intervention

12 patients in the placebo arm will receive nitrogen gas (six-hour treatment).

Who Is Running the Clinical Trial?

Robert Schilz

Lead Sponsor

Trials

1

Recruited

20+

James Reynolds

Lead Sponsor

Trials

3

Recruited

110+

Case Western Reserve University

Collaborator

Trials

314

Recruited

236,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04528771

NCT04528771 | S-Nitrosylation Therapy of COVID-19 The primary objective of this study is to provide expanded access of S-nitrosylation therapy for the treatment of severe acute respiratory syndrome coronavirus ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8962307/

Therapeutic Effects of Inhaled Nitric Oxide Therapy in ... The available data on the effect of iNO as a possible adjuvant agent for respiratory treatment in patients with COVID-19 are inconclusive. However, high-quality ...

3. nature.com nature.com/articles/s41589-022-01149-6

Targeted protein S-nitrosylation of ACE2 inhibits SARS ... We demonstrate that the viral receptor, ACE2, can be S-nitrosylated by NO-related species generated by the nitro adduct of the aminoadamantane nitrate ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04528771?tab=results

No Study Results Posted | S-Nitrosylation Therapy of COVID-19 An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12535814/

Nitric Oxide in the Treatment of COVID-19 - PubMed Central Effective therapy with NO can be used to target several stages of COVID-19 infection to prevent transmission and progression of the disease. The unique ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04528771?tab=history&a=3

Record History | ver. 3: 2022-06-20 | NCT04528771 S-Nitrosylation Therapy of COVID-19. Official Title. Proof of Concept Safety Trial for S-Nitrosylation Therapy to Improve Oxygenation Status in Severe Covid ...

7. uhhospitals.org uhhospitals.org/uh-research/find-clinical-trials-and-studies/clinical-trials-search/s-nitrosylation-therapy-study-for-covid-19-10389

S-Nitrosylation Therapy Study for COVID-19 Proof of Concept Safety Trial for S-Nitrosylation Therapy to Improve Oxygenation Status in Severe Covid-19 Patients Receiving Supplemental Oxygen Support.

8. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1155/bri/8846903

Nitric Oxide in the Treatment of COVID‐19: Nasal Sprays ... iNO therapy is related to improved oxygenation and respiratory rate for pregnant patients with severe or life-threatening COVID-19 and points ...