SepsisPhase 1/2INITIALISENCT06626984
Investigation of Novel and Established Therapies in a Human Intravenous Lipopolysaccharide Model of Sepsis
A Phase 1/2 study testing Imatinib and Compound sodium lactate solution in people with Sepsis and Fluid Overload, run by Belfast Health and Social Care Trust.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Sepsis, Fluid Overload, Endothelial Dysfunction
- What is being tested?
- Imatinib and Compound sodium lactate solution
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2024to 1 Jul 2026
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy adult volunteers aged between 18 and 40 years of age
- Informed consent to participate
Who cannot join
- 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
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- 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
Trial locations and contacts
No sites are listed yet.
About this study
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.
Read the 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:
- Intravenous fluid therapy will exacerbate the degree of vascular dysfunction and systemic inflammation observed in this model.
- Imatinib pre-treatment will attenuate the degree of vascular dysfunction and systemic inflammation observed in this model.
- Conditions
- Sepsis, Fluid Overload, Endothelial Dysfunction, Microcirculation
- Being tested
- Imatinib, Compound sodium lactate solution
- Keywords
- Intravenous Fluid Therapy, Imatinib
- Medical subject headings
- Sepsis, Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ImatinibDrug
Pre-treatment with 600mg Imatinib administered 1 hour prior to intravenous LPS.
Compound sodium lactate solutionDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Intravenous LPS only | No intervention | LPS dose 2ng/kg. |
| Intravenous LPS AND Intravenous Fluid Therapy* | Experimental | *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. Receives: Drug: Compound sodium lactate solution |
| Intravenous LPS AND Imatinib Therapy | Experimental | LPS dose 2ng/kg. Imatinib 600mg 1 hour prior to LPS administration. Receives: Drug: Imatinib |
| Intravenous LPS AND Intravenous Fluid Therapy AND Imatinib Therapy | Experimental | 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. Receives: Drug: Imatinib; Drug: Compound sodium lactate solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biomarkers of vascular and glycocalyx injury
Change in plasma biomarkers of vascular and glycocalyx injury including but not limited to - Hyaluronan
Measured: Up to 8 hours following LPS administration
Secondary outcomes (3)
Biomarkers of inflammation
Change in plasma biomarkers of inflammation including but not limited to - Interleukin-6
Measured: Up to 8 hours following LPS administration
Venous Excess Ultrasound Score
Ultrasound measure of venous congestion
Measured: Up to 8 hours following LPS administration
B-lines
Ultrasound measure of pulmonary oedema
Measured: Up to 8 hours following LPS administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2024
- Study start1 Dec 2024 (estimated)
- Primary completion1 Feb 2026 (estimated)
- Study completion1 Jul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- 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. After the first 5 participants have completed the interventions, a 2x2 factorial design will be adopted, in which participants are randomised to: 1. Intravenous fluids or no intravenous fluids, AND TO 2. Imatinib or no imatinib
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 65 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Belfast Health and Social Care Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Research Council, The Royal College of Anaesthetists
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06626984
- Sponsor's protocol ID
- 22064JS-AS
- Acronym
- INITIALISE
- Status last verified
- Aug 2024
- First submitted
- 3 May 2023
- Last updated
- 4 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of Novel and Established Therapies in a Human Intravenous Lipopolysaccharide Model of Sepsis
- ClinicalTrials.gov ID
- NCT06626984
- Acronym / sponsor ID
- INITIALISE / 22064JS-AS
- Conditions
- Sepsis, Fluid Overload, Endothelial Dysfunction, Microcirculation
- Keywords
- Intravenous Fluid Therapy, Imatinib
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 65 participants (estimated)
- Lead sponsor
- Belfast Health and Social Care TrustUniversity, hospital or other
- Collaborators
- Medical Research Council, The Royal College of Anaesthetists
- Study start
- 1 Dec 2024 (estimated)
- Primary completion
- 1 Feb 2026 (estimated)
- Study completion
- 1 Jul 2026 (estimated)
- First posted
- 4 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Intravenous fluid therapy will exacerbate the degree of vascular dysfunction and systemic inflammation observed in this model.
- Imatinib pre-treatment will attenuate the degree of vascular dysfunction and systemic inflammation observed in this model.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- 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. After the first 5 participants have completed the interventions, a 2x2 factorial design will be adopted, in which participants are randomised to: 1. Intravenous fluids or no intravenous fluids, AND TO 2. Imatinib or no imatinib
| Arm | Type | Receives |
|---|---|---|
| Intravenous LPS only | No intervention | –LPS dose 2ng/kg. |
| Intravenous LPS AND Intravenous Fluid Therapy* | Experimental | Drug: Compound sodium lactate solution*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. |
| Intravenous LPS AND Imatinib Therapy | Experimental | Drug: ImatinibLPS dose 2ng/kg. Imatinib 600mg 1 hour prior to LPS administration. |
| Intravenous LPS AND Intravenous Fluid Therapy AND Imatinib Therapy | Experimental | Drug: Imatinib, Drug: Compound sodium lactate solutionLPS 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. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Healthy adult volunteers aged between 18 and 40 years of age
- Informed consent to participate
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ImatinibPre-treatment with 600mg Imatinib administered 1 hour prior to intravenous LPS. | Drug | Intravenous LPS AND Imatinib Therapy, Intravenous LPS AND Intravenous Fluid Therapy AND Imatinib Therapy |
| Compound sodium lactate solutionTotal 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. | Drug | Intravenous LPS AND Intravenous Fluid Therapy AND Imatinib Therapy, Intravenous LPS AND Intravenous Fluid Therapy* |
Primary outcome
Biomarkers of vascular and glycocalyx injury
Time frame: Up to 8 hours following LPS administration
Change in plasma biomarkers of vascular and glycocalyx injury including but not limited to - Hyaluronan
3 secondary outcomes
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2024.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Imatinib and Compound sodium lactate solution in people with Sepsis and Fluid Overload, run by Belfast Health and Social Care Trust.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jon Silversides (+44 (0) 28 9097 6378, j.silversides@qub.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Biomarkers of vascular and glycocalyx injury (time frame: Up to 8 hours following LPS administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2024.