SNO Therapy for Transfusion Reactions

Overseen By Batuhan Degis, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: James Reynolds

Must not be taking: Anticoagulants, Antidepressants, Nitrates, others

Disqualifiers: Pregnancy, Chronic diseases, Hypertension, others

Compensation: Varies

Number of Visits: 1

Duration: 1 day

35 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether an S-nitrosylating (SNO) agent can enhance oxygen delivery to tissues during blood transfusions. Participants will receive a blood transfusion while inhaling the SNO agent to determine its effect on oxygen delivery. The study seeks healthy adults without blood disorders or conditions affecting oxygen delivery, such as sickle cell disease. Regular blood and platelet donors comfortable with blood-related procedures might find this trial suitable. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications, including phosphodiesterase 5 inhibitors, vitamin K antagonists, anticoagulants, allopurinol, beta-adrenergic blockers, tricyclic antidepressants, meperidine, nitrates, and long-term antihistamines. If you use antihistamines occasionally for allergies, the study physician will decide if you can participate.

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

Research is exploring whether S-nitrosylation (SNO) therapy can enhance oxygen delivery during blood transfusions. Previous studies suggest this method might address issues with stored blood, such as reduced oxygen delivery.

Detailed safety information is limited because the trial remains in its early stages. Early-phase trials primarily assess the safety and tolerability of the treatment in humans. So far, no serious side effects or problems with SNO therapy have been reported, indicating that researchers continue to monitor its safety closely.

Early-phase trials are designed to carefully assess safety, with participants closely monitored for potential side effects. Prospective participants should discuss any concerns with the study team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the SNO therapy for transfusion reactions because it introduces the use of an S-nitrosylating agent (SNO) during blood transfusions, which is not a common component in standard transfusion practices. Unlike typical treatments that primarily focus on managing symptoms after a transfusion reaction occurs, SNO therapy aims to prevent reactions by modifying the blood itself through inhalation of the SNO agent during the transfusion process. This approach could potentially offer a proactive way to reduce transfusion-related complications, making it a promising development in transfusion medicine.

What evidence suggests that SNO Therapy might be an effective treatment for transfusion reactions?

Research has shown that S-nitrosylation (SNO) therapy might enhance the oxygen-carrying capacity of blood during transfusions. Studies have found that a drop in S-nitrosohemoglobin (SNO-Hb) levels during transfusions can lead to reduced oxygen delivery and poorer health outcomes. In this trial, participants will receive either a blood transfusion with the SNO agent or a normal saline transfusion with the SNO agent. The SNO agent aids red blood cells in delivering oxygen more effectively. By improving oxygen delivery, SNO therapy might prevent issues like organ dysfunction that can occur after transfusions. These findings suggest that SNO treatment could make blood transfusions safer and more effective for patients. ^{2 3 6 7 8}

Who Is on the Research Team?

Batuhan Degis, MD

Principal Investigator

Case Western Reserve University

Mada Helou, MD

Principal Investigator

University Hospitals Cleveland Medical Center

Are You a Good Fit for This Trial?

Healthy, non-pregnant adults with normal hemoglobin levels (>12 g/dl) and no blood disorders or diseases affecting oxygen delivery can join. Ideal candidates are active blood/platelet donors familiar with transfusion processes. Exclusions include pregnant/breastfeeding individuals, those on certain medications like anticoagulants or antidepressants, people with irregular heart rates or lung capacity issues, and anyone with a condition that could increase study risks.

Inclusion Criteria

Hemoglobin > 12 g/dl

I am a healthy adult, not pregnant, with no blood disorders affecting oxygen delivery.

Active blood and platelet donors will be sought as study participants since these individuals are familiar with the routines for blood withdrawal and re-infusion

Exclusion Criteria

Individuals who previously received blood products to treat an acute condition will be evaluated on a case by case basis

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

Individuals who might have difficulty with the placement of a face mask (e.g. claustrophobia, uncontrolled asthma, severe allergies, sensitive skin) and/or the inhalation of a product for approximately 1-2 hr.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single intravenous blood transfusion of one unit of packed Red Blood Cells (RBCs) while inhaling an S-nitrosylating agent (SNO)

1 day

1 visit (in-person)

Monitoring

Continuous monitoring of peripheral tissue oxygenation and other physiological parameters using near infrared spectroscopy (NIRS) and blood gas analysis

24 hours

Continuous monitoring during hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of immune status, kidney function, and liver function

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Normal Saline
• Red Blood Cell
• SNO

Trial Overview The trial is testing if an S-nitrosylating (SNO) agent can better tissue oxygenation when giving packed red blood cells during transfusions. Participants will receive either the SNO therapy or a normal saline solution as part of the study to compare outcomes.

How Is the Trial Designed?

Group I: Blood transfusion with SNO agent Active Control 2 Interventions

Autologous blood transfusion packed red blood cells (RBCs) while inhaling S-nitrosylating agent (SNO) A single intra venous blood transfusion of one unit of packed Red Blood Cells (RBCs) will be given over the standard transfusion flow rate of 5 ml/min under the direction of a physician or a licensed medical professional. Inhalation of SNO agent, 20-40 parts per million will occur during the transfusion.

Group II: Normal Saline with SNO agent Placebo Group 2 Interventions

Normal Saline Transfusion while inhaling S-nitrosylating agent (SNO) A single intra venous infusion of one unit of normal saline, will be given over the standard transfusion flow rate of 5 ml/min under the direction of a physician or a licensed medical professional. Inhalation of the SNO agent at 40 parts per million, will occur during the transfusion.

Who Is Running the Clinical Trial?

James Reynolds

Lead Sponsor

Trials

3

Recruited

110+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Case Western Reserve University

Collaborator

Trials

314

Recruited

236,000+

Published Research Related to This Trial

Poly-SNO-HSA, a modified form of human serum albumin, exhibits strong pro-apoptotic effects against tumor cells, contrasting with the protective effects of its Mono-SNO-HSA counterpart.

Poly-SNO-HSA may also help overcome multidrug resistance in cancer cells, suggesting its potential as a safe and effective multifunctional antitumor agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poly-s-nitrosated albumin as a safe and effective multifunctional antitumor agent: characterization, biochemistry and possible future therapeutic applications. Ishima, Y., Kragh-Hansen, U., Maruyama, T., et al.[2021]

A new method called differential cysteine-reactive tandem mass tag (cysTMT) was developed to measure S-nitrosylation (SNO) occupancy in heart tissue, which is important for understanding protein protection against oxidation.

The study found that SNO occupancy is generally low in the myocardium at baseline but increases significantly after ischemic preconditioning, indicating that SNO plays a protective role in heart cells during stress conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measurement of S-nitrosylation occupancy in the myocardium with cysteine-reactive tandem mass tags: short communication. Kohr, MJ., Aponte, A., Sun, J., et al.[2021]

S-nitrosylated human serum albumin (SNO-HSA) has been shown to induce apoptosis in LY-80 cancer cells through mechanisms like mitochondrial depolarization and caspase-3 activation, indicating its potential as an anti-cancer therapy.

In a study involving tumor-bearing rats, SNO-HSA significantly inhibited tumor growth compared to control treatments, suggesting its efficacy as a chemopreventive or chemotherapeutic agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrosylated human serum albumin (SNO-HSA) induces apoptosis in tumor cells. Katayama, N., Nakajou, K., Ishima, Y., et al.[2017]

S-nitrosoglutathione (GSNO) has shown promising therapeutic effects in 15 human studies, indicating its potential as a nitric oxide donor for treating various conditions without inducing tolerance.

Despite its benefits, GSNO is not yet available in pharmaceutical formulations, and its clinical use is limited by its rapid and unpredictable decomposition in solutions, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current developments in the therapeutic potential of S-nitrosoglutathione, an endogenous NO-donor molecule. Hornyák, I., Pankotai, E., Kiss, L., et al.[2019]

E-Mono-SNO-HSA, a natural nitric oxide carrier, provides cytoprotective effects by inducing heme oxygenase-1, while CM-Poly-SNO-HSA, with more SNO groups, leads to faster NO transfer and promotes apoptotic cell death through ROS induction and caspase-3 activation.

The study highlights that increasing the number of SNO groups on human serum albumin can significantly alter the cellular response, demonstrating that more is not always better in terms of therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cellular uptake mechanisms and responses to NO transferred from mono- and poly-S-nitrosated human serum albumin. Ishima, Y., Yoshida, F., Kragh-Hansen, U., et al.[2017]

S-nitrosylated human serum albumin (SNO-HSA) shows promise as a novel nitric oxide (NO) donor with potential therapeutic applications, particularly in protecting cells from damage during ischemia/reperfusion events.

The presence of oleate and other fatty acids enhances the formation of SNO-HSA and its protective effects on liver cells, suggesting that these fatty acids could play a role in improving NO delivery and efficacy in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Albumin as a nitric oxide-traffic protein: characterization, biochemistry and possible future therapeutic applications. Ishima, Y., Kragh-Hansen, U., Maruyama, T., et al.[2019]

Nitric oxide (NO) functions beyond its role as a free radical; it exists in equilibrium with stable forms like S-nitrosylated hemoglobin (SNO-Hb), which plays a crucial role in regulating oxygen delivery and blood flow in the body.

Dysregulation of SNO-Hb and its related pathways is linked to several diseases, including sepsis and diabetes, suggesting that targeting these pathways could offer new therapeutic strategies for conditions like cancer and neonatal pulmonary hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transport and peripheral bioactivities of nitrogen oxides carried by red blood cell hemoglobin: role in oxygen delivery. Sonveaux, P., Lobysheva, II., Feron, O., et al.[2016]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3710799/

S-nitrosylation therapy to improve oxygen delivery ... Our findings provide evidence that adverse transfusion outcomes may reflect underlying defects in RBC function (e.g., impaired NO-based vasodilation) and are ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5867013/

S‐Nitrosohemoglobin Levels and Patient Outcome After ... ✓ We linked declines in SNO‐Hb caused by intraoperative transfusion to reductions in tissue oxygenation, organ dysfunction, and worse outcomes in young cardiac ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03999229

S-Nitrosylation (SNO) Therapy During Autologous Blood ... The Purpose of the study is to test the hypothesis that administration of an S-nitrosylating (SNO) agent can improve tissue oxygenation during transfusion of ...

4. pnas.org pnas.org/doi/10.1073/pnas.0707958104

S-nitrosohemoglobin deficiency: A mechanism for loss of ... We report that S-nitrosohemoglobin (SNO-Hb) concentrations declined rapidly after storage of fresh venous blood and that hypoxic vasodilation by banked RBCs ...

5. ascpt.onlinelibrary.wiley.com ascpt.onlinelibrary.wiley.com/doi/pdf/10.1111/cts.12530

Sâ•'Nitrosohemoglobin Levels and Patient Outcome After ... We predicted that transfusion-induced reductions in SNO-Hb would portend worse outcome, including impaired organ function and increased ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/23798386/

S-nitrosylation therapy to improve oxygen delivery of banked ... Banked blood shows reduced levels of S-nitrosohemoglobin (SNO-Hb), which in turn impairs the ability of stored RBCs to effect hypoxic vasodilation.

7. ascpt.onlinelibrary.wiley.com ascpt.onlinelibrary.wiley.com/doi/full/10.1111/cts.12530

S‐Nitrosohemoglobin Levels and Patient Outcome After ... ✓ We linked declines in SNO-Hb caused by intraoperative transfusion to reductions in tissue oxygenation, organ dysfunction, and worse outcomes ...

8. uhhospitals.org uhhospitals.org/uh-research/find-clinical-trials-and-studies/clinical-trials-search/s-nitrosylation-sno-therapy-during-autologous-blood-transfusion-17654

S-Nitrosylation (SNO) Therapy During Autologous Blood ... The purpose of the study is to find out whether giving adults an experimental drug called ethyl nitrite (ENO) can improve oxygen delivery to the body's tissues ...