Investigation of Novel and Established Therapies in a Human Intravenous Lipopolysaccharide Model of Sepsis
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Imatinib, Compound sodium lactate solution.
- Who it may be relevant to
- Registry conditions: Sepsis, Fluid Overload, Endothelial Dysfunction, Microcirculation. Basic parameters: 18 years — 40 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Center list to be confirmed — check the primary protocol.
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Overview
Sepsis is a common and life-threatening condition caused by a dysregulated host immune response to infection. Given the prominent role of endothelial breakdown and dysfunction in sepsis, therefore, there is an urgent need to establish strategies to protect the endothelium and preserve microcirculatory function. This study is a randomised clinical study investigating intravenous fluid therapy and oral imatinib therapy in healthy human volunteers exposed to intravenous lipopolysaccharide (LPS). The objective of the study is to investigate the biological effects of fluid and imatinib therapy on LPS-induced microcirculatory dysfunction.
Detailed description
The benefits of intravenous fluid administration in sepsis remain uncertain. A growing body of evidence suggests that excessive fluid administration is harmful. An association between a more positive fluid balance and mortality in critically ill patients has been repeatedly demonstrated. Moreover, emerging evidence suggests that intravenous fluid administration induces glycocalyx injury, thought to be mediated by shear stress. In sepsis the rapid administration of intravenous fluids is hypothesised to exacerbate glycocalyx injury, capillary leak and tissue oedema formation.
Recent work has highlighted the protective effects of Imatinib, a tyrosine kinase inhibitor, on endothelial barrier function in animal models of microcirculatory dysfunction as well as in patients with endothelial barrier dysfunction. Moreover, Imatinib has also been demonstrated to attenuate markers of systemic inflammation in animals with a LPS-induced lung injury model of acute respiratory distress syndrome. There is, therefore, a growing body of evidence to support a potential therapeutic role for Imatinib in disease states involving inflammatory vascular leak.
The hypothesis being tested is that:
1. Intravenous fluid therapy will exacerbate the degree of vascular dysfunction and systemic inflammation observed in this model. 2. Imatinib pre-treatment will attenuate the degree of vascular dysfunction and systemic inflammation observed in this model.
Interventions
- Drug Imatinib
Pre-treatment with 600mg Imatinib administered 1 hour prior to intravenous LPS. - Drug Compound sodium lactate solution
Total of 30 ml/kg administered 90 minutes following intravenous LPS. 30mls/kg (maximum volume of 2500mls) administered in two divided doses (15mls/kg) intravenously. Each bolus will be administered at a fixed rate of 999mls/hr.
Primary outcome measures
- Biomarkers of vascular and glycocalyx injury [Time frame: Up to 8 hours following LPS administration]
Secondary outcome measures (3)
- Biomarkers of inflammation [Time frame: Up to 8 hours following LPS administration]
- Venous Excess Ultrasound Score [Time frame: Up to 8 hours following LPS administration]
- B-lines [Time frame: Up to 8 hours following LPS administration]
Eligibility criteria
Inclusion criteria
- Healthy adult volunteers aged between 18 and 40 years of age
- Informed consent to participate
Exclusion criteria
- Current participation in a clinical trial
- Pregnant or breastfeeding
- Current history of smoking
- Alcohol intake > 21 units per week
- Regular intake of any relevant prescription or over-the-counter medication. Any regular medication use will be reviewed on a case-by-case basis as to (a) risk and (b) potential confounding effect.
- Oxygen saturation <95% breathing room air
- Abnormal findings on history, examination or laboratory tests suggestive of underlying illness (in the opinion of the clinician undertaking screening)
- History of recurrent vaso-vagal episodes
- Allergy to Imatinib
- Positive or equivocal hepatitis B or C serology result
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Allocation
- Randomized
- Model
- Factorial
- Masking
- Double blind
- Primary purpose
- Basic science
Study locations
Center list to be confirmed — check the primary protocol.
Identifiers
NCT: NCT06626984 · 22064JS-AS