Transfusion Related ComplicationPhase 1NCT03999229
S-Nitrosylation (SNO) Therapy During Autologous Blood Transfusion
A Phase 1 study testing SNO, Normal Saline and Red Blood Cell in people with Transfusion Related Complication, run by James Reynolds at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Transfusion Related Complication
- What is being tested?
- SNO, Normal Saline and Red Blood Cell
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Jul 2019to 29 Feb 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Hemoglobin > 12 g/dl
- 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.
Who cannot join
- The exclusion criteria is derived from the American Red Cross(ARC) Standard Operating Procedure (SOP) for autologous donation AND the parameters set out in the investigational new drug application (IND).
- 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.
Show all 18Show fewer
- 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 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.
- 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.
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Sindhuja Senigarapu, MD, 216-334-9277, Sindhuja.Senigarapu@uhhospitals.org
James D Reynolds, PhD, (216) 368-5727, jxr343@case.edu
About this study
Official title: Phase 1 Study of S-Nitrosylation Therapy to Improve Tissue Oxygenation During Autologous Blood Transfusion in Healthy Volunteer
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).
Read the detailed description
Transfusion is the most common therapeutic intervention employed to maintain and/or improve tissue and end-organ oxygen delivery. Despite the conceptual simplicity of this treatment recent studies indicate that RBC infusion often produces little clinical benefit and may actually harm the recipient by exacerbating rather than correcting anemia-induced tissue hypoxia.
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
- Transfusion Related Complication
- Being tested
- SNO, Normal Saline, Red Blood Cell
- Keywords
- S-Nitrosylation, Tissue Oxygenation, Anemia-induced tissue hypoxia, Red blood cell Transfusion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SNODrug
S-nitrosylating agent (SNO) Inhalation
Normal SalineDrug
Normal Saline transfusion
Red Blood CellDrug
Blood transfusion (RBCs)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: SNO; Drug: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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 will be assayed for markers of kidney function:
creatinine - milligram per deciliter
albumin - grams per deciliter
blood urea nitrogen - milligram per deciliter
This 3 blood markers are incorporated into a formula to calculate glomerular filtration rate or GFR. This is a measure of how well your kidneys are filtering your blood and if it is changing in response to transfusion or administration of the study drug.
Measured: 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 will be assayed for markers of liver function:
alanine transaminase or ALT - units per liter
aspartate aminotransferase or AST - units per liter
The individual values are determined then the AST/ALT ratio is calculated to provide further information on liver status and if it is changing in response to transfusion or administration of the study drug.
Measured: 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
The number of white blood cells is counted in each blood sample. White blood cells (also called leukocytes) are an important measure of how the immune system is working and if it is changing in response to transfusion or administration of the study drug.
leukocytes - reported as cell counts
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2019
- Study start25 Jul 2019
- Primary completion29 Feb 2028 (estimated)
- Study completion29 Feb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Transfusion Related ComplicationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- James Reynolds
- Sponsor type
- University, hospital or other
- Collaborators
- Case Western Reserve University, National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor-investigator, James Reynolds, Case Western Reserve University
- Investigators
- James D. Reynolds, PhD, Principal investigator, Case Western Reserve UniversityMada Helou, MD, Study director, University Hospitals Cleveland Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03999229
- Sponsor's protocol ID
- STUDY20221492
- Other IDs
- 5R01HL126900
- Status last verified
- Nov 2025
- First submitted
- 20 Jun 2019
- Last updated
- 2 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All of the individual participant data collected during the trial, after deidentification and analysis will be shared.
Publications
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.
PubMed 17940022Singel 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.
PubMed 15709954McMahon 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.
PubMed 16203976Pawloski 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.
PubMed 11214321VALTIS 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.
PubMed 13118742Bunn 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.
PubMed 5764013Sugerman 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.
PubMed 5458535Shah 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.
PubMed 7120526Rao 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.
PubMed 15467057Vincent 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.
PubMed 12243637Malone 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.
PubMed 12777902
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of S-Nitrosylation Therapy to Improve Tissue Oxygenation During Autologous Blood Transfusion in Healthy Volunteer
- ClinicalTrials.gov ID
- NCT03999229
- Acronym / sponsor ID
- STUDY20221492
- Conditions
- Transfusion Related Complication
- Keywords
- S-Nitrosylation, Tissue Oxygenation, Anemia-induced tissue hypoxia, Red blood cell Transfusion
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- James ReynoldsUniversity, hospital or other
- Collaborators
- Case Western Reserve University, National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 25 Jul 2019 (actual)
- Primary completion
- 29 Feb 2028 (estimated)
- Study completion
- 29 Feb 2028 (estimated)
- First posted
- 26 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
Transfusion is the most common therapeutic intervention employed to maintain and/or improve tissue and end-organ oxygen delivery. Despite the conceptual simplicity of this treatment recent studies indicate that RBC infusion often produces little clinical benefit and may actually harm the recipient by exacerbating rather than correcting anemia-induced tissue hypoxia.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Blood transfusion with SNO agent | Active comparator | Drug: SNO, Drug: Red Blood CellAutologous 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. |
| Normal Saline with SNO agent | Placebo comparator | Drug: SNO, Drug: Normal SalineNormal 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 may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Hemoglobin > 12 g/dl
- 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.
Key exclusion criteria (18 listed)
- The exclusion criteria is derived from the American Red Cross(ARC) Standard Operating Procedure (SOP) for autologous donation AND the parameters set out in the investigational new drug application (IND).
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SNOS-nitrosylating agent (SNO) Inhalation | Drug | Blood transfusion with SNO agent, Normal Saline with SNO agent |
| Normal SalineNormal Saline transfusion | Drug | Normal Saline with SNO agent |
| Red Blood CellBlood transfusion (RBCs) | Drug | Blood transfusion with SNO agent |
Primary outcome
Peripheral Tissue Oxygenation
Time frame: 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.
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.
Oxygen Utilization
Time frame: 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
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.
3 secondary outcomes
Kidney Function Test
Time frame: 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
Time frame: 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
Time frame: 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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2025.
- Background: PubMed 17940022Reynolds 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.
- Background: PubMed 15709954Singel 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.
- Background: PubMed 16203976McMahon 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.
- Background: PubMed 11214321Pawloski 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.
- Background: PubMed 13118742VALTIS 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.
- Background: PubMed 5764013Bunn 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.
- Background: PubMed 5458535Sugerman 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.
- Background: PubMed 7120526Shah 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.
- Background: PubMed 15467057Rao 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.
- Background: PubMed 12243637Vincent 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.
- Background: PubMed 12777902Malone 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.
- Individual participant dataSharing planned: Yes. All of the individual participant data collected during the trial, after deidentification and analysis will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
James D. Reynolds, PhD principal investigator
Case Western Reserve University
Mada Helou, MD study director
University Hospitals Cleveland Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SNO, Normal Saline and Red Blood Cell in people with Transfusion Related Complication, run by James Reynolds at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact James D Reynolds, PhD (216-334-9277, jxr343@case.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peripheral Tissue Oxygenation (time frame: 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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03999229, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2025.