35 Participants Needed

SNO Therapy for Transfusion Reactions

MH
JR
JD
BD
Overseen ByBatuhan Degis, MD

Trial Summary

What is the purpose of this trial?

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 packed red blood cells (RBCs).

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.

What data supports the effectiveness of SNO Therapy for transfusion reactions?

Research on S-nitrosylation (SNO) shows that it can have protective effects in the body, such as preventing damage to heart tissue. Additionally, S-nitrosothiols, which are related to SNO, have been effective in treating various conditions like asthma and cystic fibrosis, suggesting potential benefits for other medical uses.12345

Is SNO Therapy generally safe for humans?

Research on S-nitrosothiols (SNOs) suggests they are promising for therapeutic use in various conditions, and early results indicate they can be safe and effective, particularly in cancer and neonatal pulmonary hypertension. However, more research is needed to fully understand their safety profile in humans.13456

How does SNO Therapy differ from other treatments for transfusion reactions?

SNO Therapy is unique because it uses S-nitrosylated human serum albumin (SNO-HSA) to deliver nitric oxide (NO) in a controlled manner, potentially reducing side effects and improving efficacy compared to traditional NO donors. This approach may offer a novel way to manage transfusion reactions by leveraging the cytoprotective and anti-inflammatory properties of NO.12357

Research Team

BD

Batuhan Degis, MD

Principal Investigator

Case Western Reserve University

MH

Mada Helou, MD

Principal Investigator

University Hospitals Cleveland Medical Center

Eligibility Criteria

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.
See 15 more

Timeline

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

Treatment Details

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.
Participant Groups
2Treatment groups
Active Control
Placebo Group
Group I: Blood transfusion with SNO agentActive Control2 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 agentPlacebo Group2 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.

Find a Clinic Near You

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+

Findings from Research

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

References

Nitrosylated human serum albumin (SNO-HSA) induces apoptosis in tumor cells. [2017]
Cellular uptake mechanisms and responses to NO transferred from mono- and poly-S-nitrosated human serum albumin. [2017]
Poly-s-nitrosated albumin as a safe and effective multifunctional antitumor agent: characterization, biochemistry and possible future therapeutic applications. [2021]
Measurement of S-nitrosylation occupancy in the myocardium with cysteine-reactive tandem mass tags: short communication. [2021]
Current developments in the therapeutic potential of S-nitrosoglutathione, an endogenous NO-donor molecule. [2019]
Transport and peripheral bioactivities of nitrogen oxides carried by red blood cell hemoglobin: role in oxygen delivery. [2016]
Albumin as a nitric oxide-traffic protein: characterization, biochemistry and possible future therapeutic applications. [2019]