Sepsis, Endotoxemia, ImmunosuppressionLPS-BMNCT05570643
The Effects of Human Endotoxemia on Functional Capacity of Hematopoietic Stem and Progenitor Cells
A study testing LPS in people with Sepsis, Endotoxemia, Immunosuppression, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
We will investigate whether human endotoxemia induces changes in human bone marrow cells and their downstream effector cells. To comprehensively investigate underlying mechanisms behind functional and transcriptional changes in these cell types, we will use state-of-the-art systems biology techniques, including single… Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Sepsis, Endotoxemia, Immunosuppression
- What is being tested?
- LPS
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteNetherlands
- Study dates
- 5 Jan 2018to 28 Jun 2018
- Phase
- Interventional
- 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 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Written informed consent
- Age ≥18 and ≤35 yrs
- Male
- Healthy (as confirmed by medical history, examination, ECG, blood sampling)
Who cannot join
- Use of any medication
- Smoking
- History or signs of atopic syndrome (asthma, rhinitis with medication and/or eczema)
- Known anaphylaxis or hypersensitivity to the non-investigational products or their excipients.
- History or signs of hematological disease (bone marrow dysfunction):
- Thrombocytopenia (<150*10^9/ml) or anemia (hemoglobin < 8.0 mmol/L)
Show all 23Show fewer
- Abnormalities in leukocyte differential counts
- History, signs or symptoms of cardiovascular disease, in particular:
- Previous spontaneous vagal collapse
- History of atrial or ventricular arrhythmia
- Cardiac conduction abnormalities on the ECG consisting of a 2nd degree atrioventricular block or a complete left bundle branch block
- Hypertension (defined as RR systolic > 160 or RR diastolic > 90)
- Hypotension (defined as RR systolic < 100 or RR diastolic < 50)
- Renal impairment (defined as plasma creatinine >120 μmol/l)
- Liver enzyme abnormalities (above 2x the upper limit of normal)
- Medical history of any disease associated with immune deficiency
- CRP > 20 mg/L, WBC > 12x109/L or < 4 x109/L, or clinically significant acute illness, including infections, within 3 weeks before labeling day
- Previous (participation in a study with) LPS administration
- Any vaccination within 3 months prior to labeling day
- Participation in a drug trial or donation of blood 3 months prior to labeling day
- Recent hospital admission or surgery with general anesthesia (<3 months to labeling day)
- Use of recreational drugs within 21 days prior to labeling day
- Inability to personally provide written informed consent (e.g. for linguistic or mental reasons) and/or take part in the study.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Intensive Care Medicine, Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, 6500 HB
About this study
We will investigate whether human endotoxemia induces changes in human bone marrow cells and their downstream effector cells. To comprehensively investigate underlying mechanisms behind functional and transcriptional changes in these cell types, we will use state-of-the-art systems biology techniques, including single cell transcriptomics (epi)genetics, and metabolomics.
Read the detailed description
In the present study, we want to further elucidate the mechanisms behind systemic inflammation and endotoxin tolerance in vivo in humans by focusing on functional changes in hematopoietic stem and progenitor cells. Healthy male volunteers will be challenged with endotoxin to evoke a transient systemic inflammatory response. To evaluate the responses over time, blood and bone marrow aspirates will be collected at multiple timepoints. To comprehensively investigate underlying mechanisms behind functional changes, we will use state-of-the-art systems biology techniques, including single cell transcriptomics, epigenetics (e..g. scATACseq), and metabolomic. As such, this study will yield a comprehensive insight into inflammatory signaling in the different compartments of the body and will thereby improve our understanding of systemic inflammation, endotoxin tolerance,and sepsis, possibly revealing new therapeutic targets to improve sepsis outcome.
- Conditions
- Sepsis, Endotoxemia, Immunosuppression
- Being tested
- LPS, Placebo
- Keywords
- Sepsis, immunosuppression, systemic inflammation, human endotoxemia, bone marrow stem and progenitor cells, myelopoiesis, monocytes, transciptomics
- Medical subject headings
- Sepsis, Endotoxemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LPSDrug
Also called Lipopolysaccharide (LPS from Escherichia coli Type O11), Endotoxin
This is a non-investigational product. LPS is used as challenge agent to achieve a controlled inflammatory state.
PlaceboDrug
Also called NaCl
Injection of NaCl 0.9%.
| Study group | Role | What they receive |
|---|---|---|
| LPS group | Experimental | Healthy male volunteers that will receive an intravenous administration of LPS (2ng/kg) twice. Receives: Drug: LPS |
| Placebo group | Placebo comparator | Healthy male volunteers that will receive an intravenous administration of placebo (NaCl 0.9%). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in function and transcriptional pathways
The change in function and transcriptional pathways (gene expression) of hematopoietic progenitor cells and blood leukocytes (using various functional assays and single cell RNAseq) following human endotoxemia.
Measured: 15 days
Secondary outcomes (5)
Change in (Genome-wide) chromatin accessibility
The change in epigenomic profile (chromatin accessibility) of hematopoietic progenitor cells and blood leukocytes (using single cell ATACseq) following human endotoxemia.
Measured: 15 days
Change in cellular metabolism
The change in cellular metabolism of hematopoietic progenitor cells and blood leukocytes (e.g. using Seahorse analyzer, CYTOF) following human endotoxemia.
Measured: 15 days
Change in macrophage activity in the brain
To changes in tissue resident macrophages activity in the brain (assessed using 18F-DPA-714 labeling and PET examinations) following human endotoxemia.
Measured: 15 days
Life-span of blood leukocytes during homeostasis
To assessment of the life-span and transit times of different subsets of leukocytes and their progenitors in the bone marrow of humans at homeostasis (using Deuterium labeling).
Measured: 8 days
Life-span of blood leukocytes during endotoxemia
To determine the life-span and transit times of different subsets of leukocytes and their progenitors in the bone marrow of humans during human endotoxemia (using Deuterium labeling).
Measured: 8 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2022
- Study start5 Jan 2018
- Primary completion28 Jun 2018
- Study completion28 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sepsis, Endotoxemia, ImmunosuppressionStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- An pilot study to explore the effects of a LPS-challenge on functional capacity and gene expression of human stem and hematopoietic progenitor cells and blood leukocytes. Subjects will be allocated to a LPS group (n=8 healthy volunteers) that will be challenged with endotoxin twice, or to a placebo group (n=4) who will undergo the same study procedures but receive a placebo challenge (NaCl 0.9%).
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- UMC Utrecht
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05570643
- Sponsor's protocol ID
- NL61136.091.17
- Other IDs
- 2017-3337
- Acronym
- LPS-BM
- Status last verified
- Sep 2022
- First submitted
- 28 Sep 2022
- Last updated
- 6 Oct 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Single cell transcriptional/gene expression data will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Human Endotoxemia on Functional Capacity of Hematopoietic Stem and Progenitor Cells
- ClinicalTrials.gov ID
- NCT05570643
- Acronym / sponsor ID
- LPS-BM / NL61136.091.17
- Conditions
- Sepsis, Endotoxemia, Immunosuppression
- Keywords
- Sepsis, immunosuppression, systemic inflammation, human endotoxemia, bone marrow stem and progenitor cells, myelopoiesis, monocytes, transciptomics
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- UMC Utrecht
- Study start
- 5 Jan 2018 (actual)
- Primary completion
- 28 Jun 2018 (actual)
- Study completion
- 28 Jun 2018 (actual)
- First posted
- 6 Oct 2022 (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.
We will investigate whether human endotoxemia induces changes in human bone marrow cells and their downstream effector cells. To comprehensively investigate underlying mechanisms behind functional and transcriptional changes in these cell types, we will use state-of-the-art systems biology techniques, including single cell transcriptomics (epi)genetics, and metabolomics.
Detailed description
In the present study, we want to further elucidate the mechanisms behind systemic inflammation and endotoxin tolerance in vivo in humans by focusing on functional changes in hematopoietic stem and progenitor cells. Healthy male volunteers will be challenged with endotoxin to evoke a transient systemic inflammatory response. To evaluate the responses over time, blood and bone marrow aspirates will be collected at multiple timepoints. To comprehensively investigate underlying mechanisms behind functional changes, we will use state-of-the-art systems biology techniques, including single cell transcriptomics, epigenetics (e..g. scATACseq), and metabolomic. As such, this study will yield a comprehensive insight into inflammatory signaling in the different compartments of the body and will thereby improve our understanding of systemic inflammation, endotoxin tolerance,and sepsis, possibly revealing new therapeutic targets to improve sepsis outcome.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- An pilot study to explore the effects of a LPS-challenge on functional capacity and gene expression of human stem and hematopoietic progenitor cells and blood leukocytes. Subjects will be allocated to a LPS group (n=8 healthy volunteers) that will be challenged with endotoxin twice, or to a placebo group (n=4) who will undergo the same study procedures but receive a placebo challenge (NaCl 0.9%).
| Arm | Type | Receives |
|---|---|---|
| LPS group | Experimental | Drug: LPSHealthy male volunteers that will receive an intravenous administration of LPS (2ng/kg) twice. |
| Placebo group | Placebo comparator | Drug: PlaceboHealthy male volunteers that will receive an intravenous administration of placebo (NaCl 0.9%). |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Written informed consent
- Age ≥18 and ≤35 yrs
- Male
- Healthy (as confirmed by medical history, examination, ECG, blood sampling)
Key exclusion criteria (23 listed)
- Use of any medication
- Smoking
- History or signs of atopic syndrome (asthma, rhinitis with medication and/or eczema)
- Known anaphylaxis or hypersensitivity to the non-investigational products or their excipients.
- History or signs of hematological disease (bone marrow dysfunction):
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 |
|---|---|---|
| LPSAlso: Lipopolysaccharide (LPS from Escherichia coli Type O11), EndotoxinThis is a non-investigational product. LPS is used as challenge agent to achieve a controlled inflammatory state. | Drug | LPS group |
| PlaceboAlso: NaClInjection of NaCl 0.9%. | Drug | Placebo group |
Primary outcome
Change in function and transcriptional pathways
Time frame: 15 days
The change in function and transcriptional pathways (gene expression) of hematopoietic progenitor cells and blood leukocytes (using various functional assays and single cell RNAseq) following human endotoxemia.
5 secondary outcomes
Change in (Genome-wide) chromatin accessibility
Time frame: 15 days
Change in cellular metabolism
Time frame: 15 days
Change in macrophage activity in the brain
Time frame: 15 days
Life-span of blood leukocytes during homeostasis
Time frame: 8 days
Life-span of blood leukocytes during endotoxemia
Time frame: 8 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2022.
- Individual participant dataSharing planned: Yes. Single cell transcriptional/gene expression data will be shared.
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing LPS in people with Sepsis, Endotoxemia, Immunosuppression, run by Radboud University Medical Center at 1 site in Netherlands.
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 4 inclusion and 23 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: finished, as of the sponsor's last update on 6 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in function and transcriptional pathways (time frame: 15 days). 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 6 Oct 2022.