Development of Novel Non-invasive Inflammometry Following Lipopolysaccharide, Endotoxin (LPS) Challenge in Healthy Volunteers

NCT03044327 | Completed

• 1 other identifier: 15-03 DONNER
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to further profile and develop the Lipopolysaccharide, endotoxin (LPS) challenge models (both by instillation and inhalation) by investigating the utility of various non-invasive monitoring methods.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Change in the number of total cells in bronchoalveolar lavage

  change from baseline to 6 hours and 24 hours post LPS

Secondary Outcomes (3)

• The regional change in xenon uptake in dissolved-phase MRI

  change from baseline to 6 hours and 24 hours post LPS

• The regional change in oxygen transfer function assessed by MRI

  change from baseline to 6 hours and 24 hours post LPS

• The change of the number of exhaled particles

  change from baseline to 6 hours and 24 hours post LPS

Study Arms (1)

LPS challenge

OTHER

LPS inhalation and bronchial instillation

Procedure: LPS challenge

Interventions

LPS challenge PROCEDURE

LPS inhalation and bronchial instillation

LPS challenge

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Normal lung function with FEV1 predicted ≥ 80%
• Nonsmokers with a history of less than 1 pack year having been nonsmokers for at least the last five years
• Able and willing to give written informed consent

You may not qualify if:

• 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
• Clinically relevant history of allergy as judged by the investigator
• Patient unable to undergo MRI (e.g. due to claustrophobia, cardiac pacemaker, hypersensitivity to MR i.v. contrast imaging agents)
• Infections of the lower respiratory tract within 4 weeks before visit 1, visit 2, or visit 3. These patients can be rescreened starting from visit 1.
• 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
• Elevated IgE
• Intake of systemic or inhaled steroids in the previous 4 weeks before visit 1, visit 2, or visit 3
• 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
• Hannover Medical School: collaborator

Study Sites (1)

Fraunhofer ITEM

Hanover, Lower Saxony, 30625, Germany

Location

Related Publications (2)

• Larsson P, Holz O, Koster G, Postle A, Olin AC, Hohlfeld JM. Exhaled breath particles as a novel tool to study lipid composition of epithelial lining fluid from the distal lung. BMC Pulm Med. 2023 Nov 3;23(1):423. doi: 10.1186/s12890-023-02718-8.

  PMID: 37924084 DERIVED

• Holz O, Muller M, Carstensen S, Olin AC, Hohlfeld JM. Inflammatory cytokines can be monitored in exhaled breath particles following segmental and inhalation endotoxin challenge in healthy volunteers. Sci Rep. 2022 Apr 4;12(1):5620. doi: 10.1038/s41598-022-09399-z.

  PMID: 35379863 DERIVED

Study Officials

• Jens Hohlfeld, MD

  Fraunhofer-Institute of Toxicology and Experimental Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Division Director Airway Research

Study Record Dates

• First Submitted: February 1, 2017
• First Posted: February 7, 2017
• Study Start: February 15, 2017
• Primary Completion: December 31, 2017
• Study Completion: December 31, 2017
• Last Updated: May 30, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)