S-Nitrosylation (SNO) Therapy During Autologous Blood Transfusion

NCT03999229 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: STUDY202214925R01HL126900
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Transfusion Related Complication

Keywords

S-Nitrosylation; Tissue Oxygenation; Anemia-induced tissue hypoxia; Red blood cell Transfusion

Outcome Measures

Primary Outcomes (2)

• Peripheral Tissue Oxygenation

  Measurement of small vessel blood flow and oxygenation status with near infrared spectroscopy (NIRS). NIRS can record the amount of oxygenated and de-oxygenated hemoglobin (the main protein in red blood cells) using different light frequencies shined through probes attached to the skin. The tissue oxygenation measurement is expressed as a percentage based on the ratio of oxygenated to de-oxygenated hemoglobin. It is continually-measured to see if it is changing in response to transfusion or administration of the study drug.

  Monitoring is continuous once the probes are placed on the skin. It will start approximately 30 minutes prior to blood transfsuion and continue overnight and then stopped next morning when subject is discharged. Total time is up to 24 hours.

• Oxygen Utilization

  Determined by measuring arterial and venous blood oxygen levels - Blood Gas (BG) A BG is a test that measures the the levels of oxygen (O2) in the blood obtained from an artery or vein. The test is used to check the function of the patient's lungs and how well they are able to move oxygen around the body. The amount of oxygen is expressed as percent of the overall amount of hemoglobin. The difference in the amount of oxygen in arterial and venous blood is calculated as the measure of oxygen utilization and if it is changing in response to transfusion or administration of the study drug.

  Blood samples are obtained every 3 to 6 hours before during and after blood transfsuion until subject is discharged Total time is up to 24 hour

Secondary Outcomes (3)

• Kidney Function Test

  Blood samples are obtained every 3 to 6 hours before during and after blood transfsuion until subject is discharged Total time is up to 24 hour

• Liver Function Test

  Blood samples are obtained every 3 to 6 hours before during and after blood transfsuion until subject is discharged Total time is up to 24 hour

• Assessment of Immune Status

  Blood samples are obtained every 3 to 6 hours before during and after blood transfsuion until subject is discharged Total time is up to 24 hour

Study Arms (2)

Blood transfusion with SNO agent

ACTIVE COMPARATOR

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.

Drug: SNO; Drug: Red Blood Cell

Normal Saline with SNO agent

PLACEBO COMPARATOR

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.

Drug: SNO; Drug: Normal Saline

Interventions

SNO DRUG

S-nitrosylating agent (SNO) Inhalation

Blood transfusion with SNO agent; Normal Saline with SNO agent

Normal Saline DRUG

Normal Saline transfusion

Normal Saline with SNO agent

Red Blood Cell DRUG

Blood transfusion (RBCs)

Blood transfusion with SNO agent

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Hemoglobin \> 12 g/dl
• Healthy, non-pregnant adults with no pre-existing blood disorders or disease states that impact oxygen delivery.
• a. 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.

You may not qualify if:

• Individuals who are pregnant, breastfeeding, or are unwilling to avoid pregnancy during the study.
• Individuals with an anatomic anomaly that would increase the risks associated with placement of the vascular catheters.
• Individuals who report chronic diseases requiring medication of the heart, lungs, kidney, liver, etc or afflicted with any acute or chronic pathology that in the opinion of the screening physician makes them unsuitable for study.
• Individuals with a recent history of antibiotic therapy (check for underlying cause).
• Individuals unwilling to refrain from taking any phosphodiesterase 5 (PDE-5) inhibitor for at least 24 h prior to donation and/or autologous transfusion.
• Individuals taking a vitamin K antagonist (warfarin) or other anticoagulant (e.g. heparin, clopidogrel, enoxaparin or dalteparin).
• Individuals taking allopurinol, beta-adrenergic blockers, tricyclic antidepressants, meperidine (or related central nervous system (CNS) agents), or nitrates.
• Individuals with blood pressure parameters outside the normal range, i.e., higher than 130 mm Hg systolic and/or higher than 90 mm Hg diastolic; mild hypertension is acceptable by the Red Cross for blood donation.
• Individuals with heart rates outside the range of 50 to 100 beats per minutes or with a pathologic irregularity.
• a. Pulses lower than 50 may be acceptable if the study participant participates in endurance training. The study physician will be consulted for evaluation.
• \. Individuals with an inherited or acquired blood coagulation disorder, congenital methemoglobinemia, or a familial hemoglobinopathy that impacts oxygen delivery (e.g. sickle cell).
• \. Individuals with any illness that may increase the risks associated with the study.
• \. Individuals who previously received blood products to treat an acute condition will be evaluated on a case by case basis.
• \. Individuals who report an acute or chronic disease state that may impact oxygen delivery.
• \. Individuals with evidence of diminished lung capacity.

Sponsors & Collaborators

• James Reynolds: lead
• Case Western Reserve University: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

RECRUITING

Related Publications (11)

• Reynolds JD, Ahearn GS, Angelo M, Zhang J, Cobb F, Stamler JS. S-nitrosohemoglobin deficiency: a mechanism for loss of physiological activity in banked blood. Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17058-62. doi: 10.1073/pnas.0707958104. Epub 2007 Oct 11.

  PMID: 17940022 BACKGROUND

• Singel DJ, Stamler JS. Chemical physiology of blood flow regulation by red blood cells: the role of nitric oxide and S-nitrosohemoglobin. Annu Rev Physiol. 2005;67:99-145. doi: 10.1146/annurev.physiol.67.060603.090918.

  PMID: 15709954 BACKGROUND

• McMahon TJ, Ahearn GS, Moya MP, Gow AJ, Huang YC, Luchsinger BP, Nudelman R, Yan Y, Krichman AD, Bashore TM, Califf RM, Singel DJ, Piantadosi CA, Tapson VF, Stamler JS. A nitric oxide processing defect of red blood cells created by hypoxia: deficiency of S-nitrosohemoglobin in pulmonary hypertension. Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14801-6. doi: 10.1073/pnas.0506957102. Epub 2005 Oct 3.

  PMID: 16203976 BACKGROUND

• Pawloski JR, Hess DT, Stamler JS. Export by red blood cells of nitric oxide bioactivity. Nature. 2001 Feb 1;409(6820):622-6. doi: 10.1038/35054560.

  PMID: 11214321 BACKGROUND

• VALTIS DJ. Defective gas-transport function of stored red blood-cells. Lancet. 1954 Jan 16;266(6803):119-24. doi: 10.1016/s0140-6736(54)90978-2. No abstract available.

  PMID: 13118742 BACKGROUND

• Bunn HF, May MH, Kocholaty WF, Shields CE. Hemoglobin function in stored blood. J Clin Invest. 1969 Feb;48(2):311-21. doi: 10.1172/JCI105987.

  PMID: 5764013 BACKGROUND

• Sugerman HJ, Davidson DT, Vibul S, Delivoria-Papadopoulos M, Miller LD, Oski FA. The basis of defective oxygen delivery from stored blood. Surg Gynecol Obstet. 1970 Oct;131(4):733-41. No abstract available.

  PMID: 5458535 BACKGROUND

• Shah DM, Gottlieb ME, Rahm RL, Stratton HH, Barie PS, Paloski WH, Newell JC. Failure of red blood cell transfusion to increase oxygen transport or mixed venous PO2 in injured patients. J Trauma. 1982 Sep;22(9):741-6. doi: 10.1097/00005373-198209000-00004.

  PMID: 7120526 BACKGROUND

• Rao SV, Jollis JG, Harrington RA, Granger CB, Newby LK, Armstrong PW, Moliterno DJ, Lindblad L, Pieper K, Topol EJ, Stamler JS, Califf RM. Relationship of blood transfusion and clinical outcomes in patients with acute coronary syndromes. JAMA. 2004 Oct 6;292(13):1555-62. doi: 10.1001/jama.292.13.1555.

  PMID: 15467057 BACKGROUND

• Vincent JL, Baron JF, Reinhart K, Gattinoni L, Thijs L, Webb A, Meier-Hellmann A, Nollet G, Peres-Bota D; ABC (Anemia and Blood Transfusion in Critical Care) Investigators. Anemia and blood transfusion in critically ill patients. JAMA. 2002 Sep 25;288(12):1499-507. doi: 10.1001/jama.288.12.1499.

  PMID: 12243637 BACKGROUND

• Malone DL, Dunne J, Tracy JK, Putnam AT, Scalea TM, Napolitano LM. Blood transfusion, independent of shock severity, is associated with worse outcome in trauma. J Trauma. 2003 May;54(5):898-905; discussion 905-7. doi: 10.1097/01.TA.0000060261.10597.5C.

  PMID: 12777902 BACKGROUND

MeSH Terms

Interventions

Saline Solution; Erythrocyte Count

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Blood Cell Count; Cell Count; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Hematologic Tests; Investigative Techniques; Cell Physiological Phenomena; Blood Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Study Officials

• James D. Reynolds, PhD

  Case Western Reserve University

  PRINCIPAL INVESTIGATOR

• Mada Helou, MD

  University Hospitals Cleveland Medical Center

  STUDY DIRECTOR

Central Study Contacts

James D Reynolds, PhD

CONTACT

216-334-9277; jxr343@case.edu

Sindhuja Senigarapu, MD

CONTACT

216-334-9277; Sindhuja.Senigarapu@uhhospitals.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Anesthesiology and Perioperative Medicine and a member of the Case Institute for Transformative Molecular Medicine

Model Details: This is an open-label phase I trial. Healthy young adult volunteers that would considered eligible by American Red Cross standards to donate blood will be screened by qualified practitioners for eligibility to participate in the above mentioned study. We anticipate an accrual number of 35, with subjects randomized to receive their blood (n=30) or saline (n=5) while breathing an SNO agent.

Study Record Dates

• First Submitted: June 20, 2019
• First Posted: June 26, 2019
• Study Start: July 25, 2019
• Primary Completion (Estimated): February 29, 2028
• Study Completion (Estimated): February 29, 2028
• Last Updated: December 2, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, CSR
• Time Frame: Available Immediately following publication
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose.

Locations

US (1)