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Suitability of a Low Dose Lipopolysaccharide (LPS) Inhalation as a Challenge Model

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ClinicalTrials.gov Identifier: NCT01400568
Recruitment Status : Completed
First Posted : July 22, 2011
Last Update Posted : March 12, 2012
Sponsor:
Information provided by:
Fraunhofer-Institute of Toxicology and Experimental Medicine

Tracking Information
First Submitted Date  ICMJE July 19, 2011
First Posted Date  ICMJE July 22, 2011
Last Update Posted Date March 12, 2012
Study Start Date  ICMJE August 2011
Actual Primary Completion Date January 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 21, 2011)
Induced sputum [ Time Frame: 6 h after the start of LPS challenge ]
• neutrophil cell count
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01400568 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 21, 2011)
  • lung function [ Time Frame: at the end of each LPS challenge and up to 24 hours ]
    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
  • Blood samples [ Time Frame: before and 6 h after the start of LPS challenge ]
    Differential cell count
  • Exhaled breath [ Time Frame: 3 hours after the start of LPS challenge ]
    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
  • Induced sputum [ Time Frame: 6 h after the start of LPS challenge ]
    soluble biomarkers such as but not limited to Myeloperioxidase (MPO), Surfactant Protein D (SP-D), Interleukin (IL-8)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Suitability of a Low Dose Lipopolysaccharide (LPS) Inhalation as a Challenge Model
Official Title  ICMJE A Methodological Pilot Study to Assess the Suitability of a Low Dose LPS Inhalation as a Challenge Model in Early Translational Drug Development
Brief 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. 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 Type  ICMJE Interventional
Study Phase Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Healthy
Intervention  ICMJE
  • Drug: LPS challenge with nebulized LPS
    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.
  • Drug: 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.
Study Arms Experimental: LPS challenge and fluticasone propionate
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.
Interventions:
  • Drug: LPS challenge with nebulized LPS
  • Drug: fluticasone propionate (FP)
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: July 21, 2011)
12
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date January 2012
Actual Primary Completion Date January 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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)
  • 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).

Exclusion Criteria:

  • 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.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01400568
Other Study ID Numbers  ICMJE 11-06 LOPS
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Prof. Dr. Jens Hohlfeld, Fraunhofer ITEM
Study Sponsor  ICMJE Fraunhofer-Institute of Toxicology and Experimental Medicine
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jens Hohlfeld, MD, Professor Fraunhofer ITEM
PRS Account Fraunhofer-Institute of Toxicology and Experimental Medicine
Verification Date March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP