Phase 1 Study of S-Nitrosylation Therapy to Improve Tissue Oxygenation During Autologous Blood Transfusion in Healthy Volunteer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Oxygen Utilization
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
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.
干预措施: SNO (Drug)
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.
干预措施: Red Blood Cell (Drug)
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.
干预措施: SNO (Drug)
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.
干预措施: Normal Saline (Drug)
结局指标
主要结局
Oxygen Utilization
时间窗: 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.
Peripheral Tissue Oxygenation
时间窗: 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.
次要结局
- 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)
- 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)
- 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)
研究者
James Reynolds
Professor of Anesthesiology and Perioperative Medicine and a member of the Case Institute for Transformative Molecular Medicine
Case Western Reserve University