S-Nitrosylation (SNO) Therapy During Autologous Blood Transfusion

November 25, 2025 updated by: James Reynolds

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
35

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: James D Reynolds, PhD
  • Phone Number: 216-334-9277
  • Email: jxr343@case.edu

Study Contact Backup

Study Locations

  • United States
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Recruiting
        • University Hospitals Cleveland Medical Center
        • Principal Investigator:
          • Mada Helou, MD
        • Contact:
          • James D Reynolds, PhD
          • Phone Number: (216) 368-5727
          • Email: jxr343@case.edu
        • Sub-Investigator:
          • Basanta Mohapatra, MD
        • Sub-Investigator:
          • Reid Rubsamen, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 35 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Eligibility Criteria

Recruiting and studying of healthy human subjects with no pre-existing pathologic conditions from the local population. As a result the inclusion criteria is deliberately broad.

Inclusion Criteria

  1. Hemoglobin > 12 g/dl
  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

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).

  1. Individuals who are pregnant, breastfeeding, or are unwilling to avoid pregnancy during the study.
  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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: 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.
Drug: SNO
S-nitrosylating agent (SNO) Inhalation
Drug: Red Blood Cell
Blood transfusion (RBCs)
Placebo Comparator: 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.
Drug: SNO
S-nitrosylating agent (SNO) Inhalation
Drug: Normal Saline
Normal Saline transfusion

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
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
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.
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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

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.
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

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.
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

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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
James Reynolds

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Heart, Lung, and Blood Institute (NHLBI)
Case Western Reserve University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: James D. Reynolds, PhD, Case Western Reserve University
  • Study Director: Mada Helou, MD, University Hospitals Cleveland Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 25, 2019

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 29, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 29, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 20, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 25, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 26, 2019

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 2, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 25, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • STUDY20221492
  • 5R01HL126900 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All of the individual participant data collected during the trial, after deidentification and analysis will be shared.

IPD Sharing Time Frame

Available Immediately following publication

IPD Sharing Access Criteria

Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose.

IPD Sharing Supporting Information Type

  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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