EU-IPFF committed to promoting research in Pulmonary Fibrosis

Mapping Chemical and Microbiological Heterogeneity Throughout Explanted Cystic Fibrosis Lung Specimens

Study Purpose

There is plenty of evidence to suggest that the lung is not uniform. The internal surface area is 30 times that of skin, and the different bronchioles/bronchi/alveoli differ greatly in blood perfusion, temperature, oxygen tension, and pH. Also, particularly in the context of respiratory disease, notable differences are present in the structure of epithelial cells, cilia, production of mucus, and inflammatory/immune responses. All of these factors are known to impact the physiology of bacteria, yet, there is very little understanding of how they impact a) the presence/absence of particular bacterial species throughout the respiratory tract, or b) the metabolic processes used by these bacteria within the human host environment. A greater understanding of the relationships between environmental (chemical) gradients in the lungs of diseased patients (particularly those with cystic fibrosis) and the microbial communities that are present may lead to novel hypotheses about manipulation of the respiratory environment for therapeutic benefit. To investigate this further, the investigators propose to use explanted lung specimens from cystic fibrosis patients to test the following hypothesis: Hypothesis: In patients with cystic fibrosis, bacterial community composition, metabolism and environmental chemistry will vary depending on their spatial location within the airways.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Observational
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- diagnosis of cystic fibrosis.

- eligible for lung transplantation.

- exhausted other available therapies without success.

- informed consent.

Exclusion Criteria:

- there are no exclusion criteria

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT02128711
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	University of Minnesota
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Ryan C Hunter, PhD
Principal Investigator Affiliation	University of Minnesota Medical School (Microbiology)
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other, NIH
Overall Status	Recruiting
Countries	United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Cystic Fibrosis

Additional Details

To study this in greater detail, the investigators propose to study explanted tissue of CF patients that are scheduled to undergo single or double lung transplant surgery as a late-stage disease therapeutic strategy. This population will be limited to the Adult CF clinic, as pediatric subjects are rarely candidates for lung transplantation. The Adult CF Clinic performs upwards of 20 surgeries per year, and tissue that is explanted is typically discarded. Using this tissue, the investigators propose the following objectives: 1. Use 16S culture-independent sequencing to characterize the spatial distribution of bacterial pathogens throughout the lungs of cystic fibrosis patients. Lungs will be dissected into 5 separate lobes, and mucus material will be collected, homogenized, and processed for bacterial species identification. 2. Perform detailed analysis of specific gene expression throughout the respiratory tract that will serve as a proxy of environmental conditions found there. Using the same approach in Aim 1, bacterial mRNA will be extracted using established procedures. A subset of environmentally-specific genes will be detected to provide a readout of bacterial metabolism in use within the CF lung environment. 3. Use in situ hybridization imaging to visualize the spatial distribution of specific bacteria and their gene expression profiles (informed by data generated in objectives 1 and 2). The bacteria and gene candidates identified/studied in Aims 1 and Aims 2 will then be subject to analysis using in situ hybridization imaging. Tissue will be processed using microtomy and fluorescent probes will be applied to image the spatial distribution of specific bacterial species and their metabolisms throughout the respiratory tract. Information collected in these three objectives will then be paired with patient data (age, genotype, prior medical treatments, clinical microbiology data) to generate better working models of late-stage disease in CF patients.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

University of Minnesota Medical School, Minneapolis, Minnesota

Status

Recruiting

Address

University of Minnesota Medical School

Minneapolis, Minnesota, 55455

Site Contact

Jordan Dunitz, MD

[email protected]

612-624-0999