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

NCT01400568 | Completed

• 1 other identifier: 11-06 LOPS
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Induced sputum

  • neutrophil cell count

  6 h after the start of LPS challenge

Secondary Outcomes (4)

• lung function

  at the end of each LPS challenge and up to 24 hours

• Blood samples

  before and 6 h after the start of LPS challenge

• Exhaled breath

  3 hours after the start of LPS challenge

• Induced sputum

  6 h after the start of LPS challenge

Study Arms (1)

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.

Drug: LPS challenge with nebulized LPS; Drug: fluticasone propionate (FP)

Interventions

LPS challenge with nebulized LPS DRUG

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.

LPS challenge and fluticasone propionate

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.

LPS challenge and fluticasone propionate

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)
• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fraunhofer-Institute of Toxicology and Experimental Medicine: lead

Study Sites (1)

Fraunhofer ITEM

Hanover, Lower Saxony, 30625, Germany

Location

Related Publications (1)

• 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.

  PMID: 23537365 DERIVED

MeSH Terms

Interventions

Fluticasone

Intervention Hierarchy (Ancestors)

Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Jens Hohlfeld, MD, Professor

  Fraunhofer ITEM

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 19, 2011
• First Posted: July 22, 2011
• Study Start: August 1, 2011
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: March 12, 2012

Record last verified: 2012-03

Locations

DE (1)