Innate Immune ResponseLPS-FluenzNCT02642237
The Effects of Preceding LPS Administration on the Fluenz-induced Immune Response
A study testing Fluenz and LPS in people with Innate Immune Response and Immune Tolerance, run by Radboud University Medical Center.
Trial summary
To evaluate the bacterial-viral interactions between LPS and Fluenz as a model for sepsis (bacterial) and Influenza (viral) infections which are common and associated with high mortality rates in the ICU. To understand these interactions is important for the development of preventive and therapeutic interventions. 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
- Innate Immune Response, Immune Tolerance
- What is being tested?
- Fluenz and LPS
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- Dec 2015to Feb 2018
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Healthy
Who cannot join
- Pre-existent lung disease, including asthma, severe allergic rhinitis
- Use of any medication
- Current smoker or more than 5 pack-year history
- Use of recreational drugs within 21 days prior to start of the study
- Use of caffeine or alcohol within 1 day prior to start of the study
- Surgery or trauma with significant blood loss or blood donation within 3 months prior to start of the study
Show all 22Show fewer
- Participation in another clinical trial within 3 months prior to start of the study
- Frequent nosebleeds
- Recent nasal or otologic surgery
- (suspected) influenza infection during the last year
- Clinically significant acute (febrile) illness or a common cold within four weeks prior to start of the study
- History of frequent vaso-vagal collapse or of orthostatic hypotension History, signs or symptoms of cardiovascular disease.
- History of allergic reaction to Fluenz™, eggs / gelatin / gentamicin
- History of Guillain-Barré Syndrome
- Cardiac conduction abnormalities on the ECG consisting of a 2nd degree atrioventricular block or a complex bundle branch block.
- Hypertension (defined as Blood pressure (RR) systolic > 160 or RR diastolic > 90).
- Hypotension (defined as RR systolic < 100 or RR diastolic < 50).
- Renal impairment (defined as plasma creatinin >120 μmol/l).
- Liver function abnormality: alkaline phosphatase>230 U/L and/or Alanine-aminotransferase (ALT)>90 units per Liter (U/L)
- C-reactive protein (CRP) > 20 mg/L, white blood cell count (WBC) > 12x109/L
- Vaccination with influenza this season
- Recent vaccination
About this study
Official title: The Effects of an Endotoxin Challenge on the Immune Response Elicited by a Subsequent Challenge With Fluenz in Healthy Volunteers, an Explorative Study
To evaluate the bacterial-viral interactions between LPS and Fluenz as a model for sepsis (bacterial) and Influenza (viral) infections which are common and associated with high mortality rates in the ICU. To understand these interactions is important for the development of preventive and therapeutic interventions.
Read the detailed description
The Influenza virus is known for its severe course of infection and systemic effects, associated with high mortality rates. Recent work has shown that influenza promotes susceptibility for secondary bacterial infections, thereby worsening the prognosis. While it has become clear that bacterial infections induce an immunosuppressed state in which the immune response against viral infections is attenuated1, it is unknown how a bacterial infection, such as in sepsis, influences the susceptibility and immune response to influenza. The sepsis-induced immunosuppressive state, called "immunoparalysis", may be a major contributor to this increased vulnerability. Because of the high mortality rates of both sepsis and influenza, it is of main importance to understand this interaction for the development of putative preventive and therapeutic interventions in ICU patients.
Human endotoxemia represents a model of systemic inflammation, mimicking bacterial sepsis and subsequent development of immunoparalysis. The live, attenuated, quadrivalent influenza vaccine "Fluenz™" is registered in the European Union and can be used as a surrogate for an actual influenza infection. In this study, we want to investigate the effects of an endotoxemia challenge on the Fluenz™-induced inflammatory response to present unique in vivo data on mechanistic interactions of systemic LPS followed by mucosal Fluenz™, thereby providing clues regarding the increased vulnerability towards viral infections in septic patients and open up new avenues to investigate therapeutic measures to prevent this. Furthermore, it provides important implications regarding the safety and efficacy of the vaccine in (post)septic or immunocompromised patients.
Objective: Our primary objective is to investigate the effects of endotoxin-induced systemic inflammation and subsequent development of endotoxin tolerance on the inflammatory response following Fluenz administration in vivo. To evaluate whether these effects involve local and/or systemic inflammation, symptoms, temperature and peak expiratory flow will be measured. Next, local inflammatory parameters are measured in nasal wash and systemic inflammatory parameters are measured in blood. Furthermore, we want to evaluate whether preceding endotoxemia influences the viral shedding of influenza in nasal wash. Also, changes in the mucosal microbiome, transcriptome and metabolome will be assessed. Finally, mitochondrial function and mental strength during human endotoxemia will be assessed.
- Conditions
- Innate Immune Response, Immune Tolerance
- Being tested
- Fluenz, placebo, LPS
- Keywords
- Fluenz, innate immune response, endotoxin tolerance, priming
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FluenzBiological
intranasal inoculation with Fluenz
placeboOther
LPSOther
| Study group | Role | What they receive |
|---|---|---|
| LPS-Fluenz | Experimental | Healthy volunteers administered intravenously with endotoxin, followed by an intranasal inoculation with Fluenz, a live-attenuated influenza vaccin Receives: Biological: Fluenz; Other: LPS |
| Placebo-Fluenz | Placebo comparator | Healthy volunteers administered intravenously with placebo, followed by an intranasal inoculation with Fluenz, a live-attenuated influenza vaccin Receives: Biological: Fluenz; Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak Levels of Interferon Gamma-induced Protein 10 (IP-10) in Nasal Wash Fluid
Interferon gamma-induced protein 10 is a marker of viral-induced inflammation. Higher levels indicate a more pronounced inflammatory response upon a viral infection.
Measured: 35 days after FLuenz inoculation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2015 (estimated)
- Study startDec 2015
- Primary completionJan 2017
- Study completionFeb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Innate Immune ResponseStudies 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Matthijs Kox, Radboud University Medical Center
- Investigators
- Peter Pickkers, Prof. Dr., Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02642237
- Sponsor's protocol ID
- LPS-Fluenz
- Acronym
- LPS-Fluenz
- Status last verified
- May 2019
- First submitted
- 14 Dec 2015
- Last updated
- 14 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of an Endotoxin Challenge on the Immune Response Elicited by a Subsequent Challenge With Fluenz in Healthy Volunteers, an Explorative Study
- ClinicalTrials.gov ID
- NCT02642237
- Acronym / sponsor ID
- LPS-Fluenz / LPS-Fluenz
- Conditions
- Innate Immune Response, Immune Tolerance
- Keywords
- Fluenz, innate immune response, endotoxin tolerance, priming
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Dec 2015 (actual)
- Primary completion
- Jan 2017 (actual)
- Study completion
- Feb 2018 (actual)
- First posted
- 30 Dec 2015 (estimated)
- Results
- Posted 19 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the bacterial-viral interactions between LPS and Fluenz as a model for sepsis (bacterial) and Influenza (viral) infections which are common and associated with high mortality rates in the ICU. To understand these interactions is important for the development of preventive and therapeutic interventions.
Detailed description
The Influenza virus is known for its severe course of infection and systemic effects, associated with high mortality rates. Recent work has shown that influenza promotes susceptibility for secondary bacterial infections, thereby worsening the prognosis. While it has become clear that bacterial infections induce an immunosuppressed state in which the immune response against viral infections is attenuated1, it is unknown how a bacterial infection, such as in sepsis, influences the susceptibility and immune response to influenza. The sepsis-induced immunosuppressive state, called "immunoparalysis", may be a major contributor to this increased vulnerability. Because of the high mortality rates of both sepsis and influenza, it is of main importance to understand this interaction for the development of putative preventive and therapeutic interventions in ICU patients.
Human endotoxemia represents a model of systemic inflammation, mimicking bacterial sepsis and subsequent development of immunoparalysis. The live, attenuated, quadrivalent influenza vaccine "Fluenz™" is registered in the European Union and can be used as a surrogate for an actual influenza infection. In this study, we want to investigate the effects of an endotoxemia challenge on the Fluenz™-induced inflammatory response to present unique in vivo data on mechanistic interactions of systemic LPS followed by mucosal Fluenz™, thereby providing clues regarding the increased vulnerability towards viral infections in septic patients and open up new avenues to investigate therapeutic measures to prevent this. Furthermore, it provides important implications regarding the safety and efficacy of the vaccine in (post)septic or immunocompromised patients.
Objective: Our primary objective is to investigate the effects of endotoxin-induced systemic inflammation and subsequent development of endotoxin tolerance on the inflammatory response following Fluenz administration in vivo. To evaluate whether these effects involve local and/or systemic inflammation, symptoms, temperature and peak expiratory flow will be measured. Next, local inflammatory parameters are measured in nasal wash and systemic inflammatory parameters are measured in blood. Furthermore, we want to evaluate whether preceding endotoxemia influences the viral shedding of influenza in nasal wash. Also, changes in the mucosal microbiome, transcriptome and metabolome will be assessed. Finally, mitochondrial function and mental strength during human endotoxemia will be assessed.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LPS-Fluenz | Experimental | Biological: Fluenz, Other: LPSHealthy volunteers administered intravenously with endotoxin, followed by an intranasal inoculation with Fluenz, a live-attenuated influenza vaccin |
| Placebo-Fluenz | Placebo comparator | Biological: Fluenz, Other: placeboHealthy volunteers administered intravenously with placebo, followed by an intranasal inoculation with Fluenz, a live-attenuated influenza vaccin |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Healthy
Key exclusion criteria (22 listed)
- Pre-existent lung disease, including asthma, severe allergic rhinitis
- Use of any medication
- Current smoker or more than 5 pack-year history
- Use of recreational drugs within 21 days prior to start of the study
- Use of caffeine or alcohol within 1 day prior to start of the study
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 |
|---|---|---|
| Fluenzintranasal inoculation with Fluenz | Biological | LPS-Fluenz, Placebo-Fluenz |
| placebo | Other | Placebo-Fluenz |
| LPS | Other | LPS-Fluenz |
Primary outcome
Peak Levels of Interferon Gamma-induced Protein 10 (IP-10) in Nasal Wash Fluid
Time frame: 35 days after FLuenz inoculation
Interferon gamma-induced protein 10 is a marker of viral-induced inflammation. Higher levels indicate a more pronounced inflammatory response upon a viral infection.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Peter Pickkers, Prof. Dr. principal investigator
Radboud University Medical Center
Questions about this trial
What is this clinical trial studying?
A study testing Fluenz and LPS in people with Innate Immune Response and Immune Tolerance, run by Radboud University Medical Center.
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 1 inclusion and 22 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 14 May 2019. 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. 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?
Yes. Results are posted in the registry (first posted 19 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Peak Levels of Interferon Gamma-induced Protein 10 (IP-10) in Nasal Wash Fluid (time frame: 35 days after FLuenz inoculation). 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 14 May 2019.