HealthyNCT01400568
Suitability of a Low Dose Lipopolysaccharide (LPS) Inhalation as a Challenge Model
A study testing LPS challenge with nebulized LPS and fluticasone propionate (FP) in people with Healthy, run by Fraunhofer-Institute of Toxicology and Experimental Medicine at 1 site in Germany.
Trial summary
This pilot study is planned to assess the suitability of a low dose Lipopolysaccharide (LPS) inhalation as a challenge model. As LPS effects are based on a different mode of action, this challenge model will provide the possibility to test a wider spectrum of potential drugs in the future. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- LPS challenge with nebulized LPS and fluticasone propionate (FP)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteGermany
- Study dates
- Aug 2011to Jan 2012
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Able and willing to give written informed consent
- Healthy male and female nonsmokers, aged 18 to 55 years, with a history of less than 1 pack year having been nonsmokers for at least the last five years
- FEV1 ≥ 80 % of predicted, FEV1/FVC ≥ 70 %.
- Available to complete all study measurements
- Subjects must be able to produce adequate sputum (≥ 1× 106 total cells, ≥ 50 % cell viability, ≤ 20 % squamous epithelial cells)
- Negative methacholine challenge (> 8 mg/mL)
Show all 9Show fewer
- Women will be considered for inclusion if they are:
- Not pregnant, as confirmed by pregnancy test (see flow chart), and not nursing. Of non-child bearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is pre-menarchial or post-menopausal, with documented proof of hysterectomy or tubal ligation, or meets clinical criteria for menopause and has been amenorrhoeic for more than 1 year prior to the screening visit).
- Of childbearing potential and using a highly effective method of contraception during the entire study (vasectomised partner, sexual abstinence - the lifestyle of the female should be such that there is complete abstinence from intercourse from two weeks prior to the first dose of study medication until at least 72 hours after treatment -, implants, injectables, combined oral contraceptives, hormonal IUDs or double-barrier methods, i.e. any double combination of IUD, condom with spermicidal gel, diaphragm, sponge, and cervical cap).
Who cannot join
- Upper or lower respiratory tract infection in the last four weeks prior to screening
- Past or present disease, which as judged by the investigator, may affect the outcome of the study. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, hematological disease, neurological disease, psychiatric disease, endocrine disease, infectious disease, inflammatory disease or pulmonary disease (including but not confined to asthma, tuberculosis, bronchiectasis or cystic fibrosis)
- Regular intake of any prescribed or over the counter medication. Exceptions include paracetamol for pain relief, oral contraceptive medication, hormonal replacement therapy, dietary and vitamin supplements
- Any clinically relevant abnormal findings in physical examination, clinical chemistry, hematology, urinalysis, vital signs or ECG at Visit 1, which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or may influence the results of the study, or the subject's ability to participate in the study.
- Administration of corticosteroids within the last 2 weeks prior to screening. Administration of topical corticosteroids within the last 2 weeks prior to screening is permitted at the discretion of the investigator.
- History of drug or alcohol abuse
- Risk of non-compliance with study procedures
- Suspected inability to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Methodological Pilot Study to Assess the Suitability of a Low Dose LPS Inhalation as a Challenge Model in Early Translational Drug Development
This pilot study is planned to assess the suitability of a low dose Lipopolysaccharide (LPS) inhalation as a challenge model. As LPS effects are based on a different mode of action, this challenge model will provide the possibility to test a wider spectrum of potential drugs in the future. Provided that the LPS response is reproducible, it is planned to test whether a single high dose of inhaled steroid can serve as a positive control in the LPS model. Another major aim of the study is to test a variety of novel tools for the non-invasive assessment of airway inflammation induced by LPS challenge.
Read the detailed description
In this study, airway inflammation will be induced by LPS inhalation. In case a neutrophilic airway inflammation can be safely induced by inhaled LPS, the LPS challenge will be repeated. If neutrophil airway inflammation after LPS challenge is reproducible LPS challenge will be repeated after pre-treatment with a single high dose of inhaled fluticasone propionate.
To determine airway inflammation, the subjects' exhaled breath will be analyzed by different techniques, and blood samples as well as induced sputum will be collected.
- Conditions
- Healthy
- Being tested
- LPS challenge with nebulized LPS, fluticasone propionate (FP)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LPS challenge with nebulized LPSDrug
20,000 EU of Clinical Center Reference Endotoxine (CCRE) will be applied by an AKITA® Jet Nebulizer under the constant supervision of the site staff.
fluticasone propionate (FP)Drug
The dosage of FP will be 2 mg. This dosage will be inhaled by 4 puffs of Flutide® forte 500 Diskus® 500 µg / dose according to the package insert.
| Study group | Role | What they receive |
|---|---|---|
| LPS challenge and fluticasone propionate | Experimental | In case LPS induced airway inflammation is reproducible, the effect of a single high dose of inhaled fluticasone propionate will be assessed after a 4-week wash-out period. Receives: Drug: LPS challenge with nebulized LPS; Drug: fluticasone propionate (FP) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Induced sputum
- neutrophil cell count
Measured: 6 h after the start of LPS challenge
Secondary outcomes (4)
lung function
Change of lung function directly at the end of each challenge as well as up to 24 h after the end of exposure compared with baseline
Measured: at the end of each LPS challenge and up to 24 hours
Blood samples
Differential cell count
Measured: before and 6 h after the start of LPS challenge
Exhaled breath
Pre-concentrated samples (30 L, 10-15 exhalations) on a specific substrate for later analysis by Gas Chromatorgraphy - Mass Spectrometry (GC-MS) or Smart-Nose and exhaled breath temperature
Measured: 3 hours after the start of LPS challenge
Induced sputum
soluble biomarkers such as but not limited to Myeloperioxidase (MPO), Surfactant Protein D (SP-D), Interleukin (IL-8)
Measured: 6 h after the start of LPS challenge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2011 (estimated)
- Study startAug 2011
- Primary completionJan 2012
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies 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 N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fraunhofer-Institute of Toxicology and Experimental Medicine
- Sponsor type
- University, hospital or other
- Investigators
- Jens Hohlfeld, MD, Professor, Principal investigator, Fraunhofer ITEM
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01400568
- Sponsor's protocol ID
- 11-06 LOPS
- Status last verified
- Mar 2012
- First submitted
- 19 Jul 2011
- Last updated
- 12 Mar 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Janssen O, Schaumann F, Holz O, Lavae-Mokhtari B, Welker L, Winkler C, Biller H, Krug N, Hohlfeld JM. Low-dose endotoxin inhalation in healthy volunteers--a challenge model for early clinical drug development. BMC Pulm Med. 2013 Mar 28;13:19. doi: 10.1186/1471-2466-13-19.
PubMed 23537365
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Methodological Pilot Study to Assess the Suitability of a Low Dose LPS Inhalation as a Challenge Model in Early Translational Drug Development
- ClinicalTrials.gov ID
- NCT01400568
- Acronym / sponsor ID
- 11-06 LOPS
- Conditions
- Healthy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Fraunhofer-Institute of Toxicology and Experimental MedicineUniversity, hospital or other
- Study start
- Aug 2011
- Primary completion
- Jan 2012 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 22 Jul 2011 (estimated)
- 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.
This pilot study is planned to assess the suitability of a low dose Lipopolysaccharide (LPS) inhalation as a challenge model. As LPS effects are based on a different mode of action, this challenge model will provide the possibility to test a wider spectrum of potential drugs in the future. Provided that the LPS response is reproducible, it is planned to test whether a single high dose of inhaled steroid can serve as a positive control in the LPS model. Another major aim of the study is to test a variety of novel tools for the non-invasive assessment of airway inflammation induced by LPS challenge.
Detailed description
In this study, airway inflammation will be induced by LPS inhalation. In case a neutrophilic airway inflammation can be safely induced by inhaled LPS, the LPS challenge will be repeated. If neutrophil airway inflammation after LPS challenge is reproducible LPS challenge will be repeated after pre-treatment with a single high dose of inhaled fluticasone propionate.
To determine airway inflammation, the subjects' exhaled breath will be analyzed by different techniques, and blood samples as well as induced sputum will be collected.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LPS challenge and fluticasone propionate | Experimental | Drug: LPS challenge with nebulized LPS, Drug: fluticasone propionate (FP)In case LPS induced airway inflammation is reproducible, the effect of a single high dose of inhaled fluticasone propionate will be assessed after a 4-week wash-out period. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Able and willing to give written informed consent
- Healthy male and female nonsmokers, aged 18 to 55 years, with a history of less than 1 pack year having been nonsmokers for at least the last five years
- FEV1 ≥ 80 % of predicted, FEV1/FVC ≥ 70 %.
- Available to complete all study measurements
- Subjects must be able to produce adequate sputum (≥ 1× 106 total cells, ≥ 50 % cell viability, ≤ 20 % squamous epithelial cells)
Key exclusion criteria (8 listed)
- Upper or lower respiratory tract infection in the last four weeks prior to screening
- Past or present disease, which as judged by the investigator, may affect the outcome of the study. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, hematological disease, neurological disease, psychiatric disease, endocrine disease, infectious disease, inflammatory disease or pulmonary disease (including but not confined to asthma, tuberculosis, bronchiectasis or cystic fibrosis)
- Regular intake of any prescribed or over the counter medication. Exceptions include paracetamol for pain relief, oral contraceptive medication, hormonal replacement therapy, dietary and vitamin supplements
- Any clinically relevant abnormal findings in physical examination, clinical chemistry, hematology, urinalysis, vital signs or ECG at Visit 1, which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or may influence the results of the study, or the subject's ability to participate in the study.
- Administration of corticosteroids within the last 2 weeks prior to screening. Administration of topical corticosteroids within the last 2 weeks prior to screening is permitted at the discretion of the investigator.
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 |
|---|---|---|
| LPS challenge with nebulized LPS20,000 EU of Clinical Center Reference Endotoxine (CCRE) will be applied by an AKITA® Jet Nebulizer under the constant supervision of the site staff. | Drug | LPS challenge and fluticasone propionate |
| fluticasone propionate (FP)The dosage of FP will be 2 mg. This dosage will be inhaled by 4 puffs of Flutide® forte 500 Diskus® 500 µg / dose according to the package insert. | Drug | LPS challenge and fluticasone propionate |
Primary outcome
Induced sputum
Time frame: 6 h after the start of LPS challenge
• neutrophil cell count
4 secondary outcomes
lung function
Time frame: at the end of each LPS challenge and up to 24 hours
Blood samples
Time frame: before and 6 h after the start of LPS challenge
Exhaled breath
Time frame: 3 hours after the start of LPS challenge
Induced sputum
Time frame: 6 h after the start of LPS challenge
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 12 Mar 2012.
- Derived from this study: PubMed 23537365Janssen O, Schaumann F, Holz O, Lavae-Mokhtari B, Welker L, Winkler C, Biller H, Krug N, Hohlfeld JM. Low-dose endotoxin inhalation in healthy volunteers--a challenge model for early clinical drug development. BMC Pulm Med. 2013 Mar 28;13:19. doi: 10.1186/1471-2466-13-19.
Related trials for Healthy
Recruiting
THE EFFECTS OF GAME-BASED EXERCISE PROGRAMS
Physical Activity, Body Image
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
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.
Jens Hohlfeld, MD, Professor principal investigator
Fraunhofer ITEM
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 challenge with nebulized LPS and fluticasone propionate (FP) in people with Healthy, run by Fraunhofer-Institute of Toxicology and Experimental Medicine at 1 site in Germany.
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 9 inclusion and 8 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 12 Mar 2012. 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 Germany. 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. 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?
Induced sputum (time frame: 6 h after the start of LPS challenge). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01400568, which also lists 1 linked publication.
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 12 Mar 2012.