S-Nitrosylation (SNO) Therapy During Autologous Blood Transfusion
NCT ID: NCT03999229
Last Updated: 2025-12-02
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1
35 participants
INTERVENTIONAL
2019-07-25
2028-02-29
Brief Summary
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Detailed Description
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The main driver/regulator of tissue oxygenation is blood flow not blood oxygen content. In turn flow into the microvasculature is controlled by small molecules called S-nitrosothiols (SNOs), the most important of which is S-nitrosylated hemoglobin (SNO-Hb).
The investigators determined that storage of human blood leads to rapid losses in SNO-Hb that are precisely paralleled by losses in the ability of stored RBCs to dilate blood vessels and thereby deliver oxygen. The investigators have now recently completed an autologous human blood transfusion that confirms the pre-clinical findings in that administration of 1 unit of packed RBCs to young healthy subjects did not improve tissue oxygenation and reduced circulating SNO-Hb levels.
This novel mechanism for the loss of physiological activity in banked blood and, more importantly, a putative intervention for its correction, raise the possibility that restoration of NO bioactivity could correct the deficit in oxygen delivery. As such, The Investigators plan to repeat our transfusion study with the addition of administering an S-nitrosylating agent during RBC infusion.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Blood transfusion with SNO agent
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.
SNO
S-nitrosylating agent (SNO) Inhalation
Red Blood Cell
Blood transfusion (RBCs)
Normal Saline with SNO agent
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.
SNO
S-nitrosylating agent (SNO) Inhalation
Normal Saline
Normal Saline transfusion
Interventions
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SNO
S-nitrosylating agent (SNO) Inhalation
Normal Saline
Normal Saline transfusion
Red Blood Cell
Blood transfusion (RBCs)
Eligibility Criteria
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Inclusion Criteria
2. Healthy, non-pregnant adults with no pre-existing blood disorders or disease states that impact oxygen delivery.
2a. 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
2. Individuals with an anatomic anomaly that would increase the risks associated with placement of the vascular catheters.
3. 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.
4. Individuals with a recent history of antibiotic therapy (check for underlying cause).
5. Individuals unwilling to refrain from taking any phosphodiesterase 5 (PDE-5) inhibitor for at least 24 h prior to donation and/or autologous transfusion.
6. Individuals taking a vitamin K antagonist (warfarin) or other anticoagulant (e.g. heparin, clopidogrel, enoxaparin or dalteparin).
7. Individuals taking allopurinol, beta-adrenergic blockers, tricyclic antidepressants, meperidine (or related central nervous system (CNS) agents), or nitrates.
8. Individuals on long-term antihistamine therapy 8a. The study physician will determine on a case by case basis the suitability for inclusion of individuals who control seasonal or acute allergies with occasional antihistamine use.
9. 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.
10. Individuals with heart rates outside the range of 50 to 100 beats per minutes or with a pathologic irregularity.
10a. Pulses lower than 50 may be acceptable if the study participant participates in endurance training. The study physician will be consulted for evaluation.
11\. Individuals with an inherited or acquired blood coagulation disorder, congenital methemoglobinemia, or a familial hemoglobinopathy that impacts oxygen delivery (e.g. sickle cell).
12\. Individuals with any illness that may increase the risks associated with the study.
13\. Individuals who previously received blood products to treat an acute condition will be evaluated on a case by case basis.
14\. Individuals who report an acute or chronic disease state that may impact oxygen delivery.
15\. Individuals with evidence of diminished lung capacity.
16\. 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 2-3 hours.
18 Years
35 Years
ALL
Yes
Sponsors
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Case Western Reserve University
OTHER
National Heart, Lung, and Blood Institute (NHLBI)
NIH
James Reynolds
OTHER
Responsible Party
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James Reynolds
Professor of Anesthesiology and Perioperative Medicine and a member of the Case Institute for Transformative Molecular Medicine
Principal Investigators
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James D. Reynolds, PhD
Role: PRINCIPAL_INVESTIGATOR
Case Western Reserve University
Mada Helou, MD
Role: STUDY_DIRECTOR
University Hospitals Cleveland Medical Center
Locations
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University Hospitals Cleveland Medical Center
Cleveland, Ohio, United States
Countries
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Central Contacts
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Facility Contacts
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References
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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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Other Identifiers
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STUDY20221492
Identifier Type: -
Identifier Source: org_study_id
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