Investigation of novel and established therapies in a human intravenous LPS model of sepsis

• Research type

  Research Study

• Full title

  Investigation of novel and established therapies in a human intravenous LPS model of sepsis (INITIALISE)

• IRAS ID

  1006559

• Contact name

  Jonathan Silversides

• Contact email

  j.silversides@qub.ac.uk

• Sponsor organisation

  Belfast Health and Social Care Trust

• Research summary

  The problem: Sepsis is a common, out-of-control immune response to infection, resulting in abnormal blood flow so that some areas may not receive enough blood and oxygen. Sepsis also causes damage to special cells in blood vessels called endothelial cells. The vessels become “leaky”, allowing fluid to move into surrounding areas. This leaked fluid makes it hard for oxygen to reach the cells where it is needed. A key treatment for sepsis is to give fluids intravenously in order to improve blood flow. However, fluid may cause more damage to blood vessels, thereby making swelling worse which makes it even more difficult for oxygen to be delivered where it is required. It is important to establish the effects of fluid on blood vessels and blood flow in sepsis, as it may be either helping or causing harm. It is also important to find out if any drugs can protect blood vessels from damage or control the immune response.
  The Research Proposal: Volunteers will receive intravenous lipopolysaccharide (LPS). LPS causes a very mild sepsis-like state for a few hours, similar to a mild flu. This will be carried out in a medical research centre. We will use a camera to examine small blood vessels under the tongue before and after giving LPS. We will use ultrasound technology to assess for fluid leakage and fluid accumulation. After giving LPS, some volunteers will be given intravenous fluids, and some not. By comparing the two groups, we can see what effect fluid has on blood flow, on small blood vessels. Moreover, some volunteers will receive fluid only to ascertain the impact this has. We also plan to investigate a drug called Imatinib which may help protect endothelial cells. Some volunteers will be given imatinib and some will not. By comparing the blood flow and blood vessels between groups we will be able to see if imatinib has any beneficial effects.

• REC name

  London - Westminster Research Ethics Committee

• REC reference

  23/LO/0394

• Date of REC Opinion

  9 Jan 2024

• REC opinion

  Further Information Favourable Opinion