A Phase 1/2 interventional study of Imatinib and Compound sodium lactate solution in Sepsis, Fluid Overload and Endothelial Dysfunction, sponsored by Belfast Health and Social Care Trust. Not yet recruiting. Open to participants aged 18 Years to 40 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-10-04.
Sponsored by Belfast Health and Social Care Trust · Phase 1/2, Interventional, and Basic science
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.
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:
2,416 studies on the registry are indexed under Sepsis; 541 are open to participants now.
This study's planned enrollment of 65 is below the median of 102 across 1,165 interventional studies indexed under Sepsis.
Browse Sepsis studies →Belfast Health and Social Care Trust is the lead sponsor of 45 studies on the registry; 7 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LPS dose 2ng/kg.
\*The first 5 participants recruited to this study will receive intravenous fluid therapy only. This will allow us to directly elucidate the effects of intravenous fluid therapy on markers of vascular injury, markers of systemic inflammation, microcirculatory function and venous congestion in healthy volunteers. LPS dose 2ng/kg. Intravenous fluid 30ml/kg in total (maximum volume of 2500mls). Administered in two divided doses (15mls/kg) intravenously. Each bolus will be administered at a fixed rate of 999mls/hr. The administration is to commence 90 minutes following intravenous LPS.
Drug: Compound sodium lactate solution
LPS dose 2ng/kg. Imatinib 600mg 1 hour prior to LPS administration.
Drug: Imatinib
LPS dose 2ng/kg. Intravenous fluid 30ml/kg in total (maximum volume of 2500mls). Administered in two divided doses (15mls/kg) intravenously. Each bolus will be administered at a fixed rate of 999mls/hr. The administration is to commence 90 minutes following intravenous LPS. Imatinib 600mg 1 hour prior to LPS administration.
Drug: Imatinib · Drug: Compound sodium lactate solution
Pre-treatment with 600mg Imatinib administered 1 hour prior to intravenous LPS.
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.
Biomarkers of vascular and glycocalyx injury
Change in plasma biomarkers of vascular and glycocalyx injury including but not limited to - Hyaluronan
Time frame: Up to 8 hours following LPS administration
Biomarkers of inflammation
Change in plasma biomarkers of inflammation including but not limited to - Interleukin-6
Time frame: Up to 8 hours following LPS administration
Venous Excess Ultrasound Score
Ultrasound measure of venous congestion
Time frame: Up to 8 hours following LPS administration
B-lines
Ultrasound measure of pulmonary oedema
Time frame: Up to 8 hours following LPS administration
No study locations are listed for this record.
Plan to share: No — No individual participant data will be available to share with other researchers. Anonymised data will be grouped into a database which may be shared with other researchers.
No publications or documents are linked to this record.
This study is not yet recruiting, as verified in Aug 2024. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Imatinib · Ringer's Lactate
Belfast Health and Social Care Trust