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

Development of Novel Non-invasive Inflammometry Following LPS Challenge in Healthy Volunteers

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Procedure: LPS challenge

Detailed Description

The hypothesis of the project is that local inflammatory changes in the lung induced by LPS can be captured by gas-enhanced Magnetic resonance imaging (MRI) and analysis of exhaled breath. While MRI is able to provide localized information on inflammatory processes, exhaled breath analysis can capture integral information over time. Assuming that these novel techniques correlate with cellular measures of inflammation, repetitive measurements to investigate onset and duration of action of investigational new drugs will be made possible.

The evaluation whether LPS induced changes in the lung can be captured and monitored by MRI will be performed by correlation of multiple endpoints describing the cellular composition of the airways with variables derived from MRI and breath analysis.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625
      • Fraunhofer ITEM

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female healthy subjects, aged 18-65 years. 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).

• 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

Exclusion Criteria:

• • 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: LPS challenge; LPS inhalation and bronchial instillation	Procedure: LPS challenge; LPS inhalation and bronchial instillation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in the number of total cells in bronchoalveolar lavage	change from baseline to 6 hours and 24 hours post LPS

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Fraunhofer-Institute of Toxicology and Experimental Medicine
• Collaborators: Hannover Medical School
• Investigators: Principal Investigator: Jens Hohlfeld, MD, Fraunhofer-Institute of Toxicology and Experimental Medicine

Publications and helpful links

General Publications

• Holz O, Müller 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2017
• Primary Completion (Actual): December 31, 2017
• Study Completion (Actual): December 31, 2017

Study Registration Dates

• First Submitted: February 1, 2017
• First Submitted That Met QC Criteria: February 2, 2017
• First Posted (Estimate): February 7, 2017

Study Record Updates

• Last Update Posted (Actual): May 30, 2018
• Last Update Submitted That Met QC Criteria: May 29, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: 15-03 DONNER

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No