Characterization of Apolipoprotein A-I Pathways in Idiopathic Pulmonary Fibrosis

Background:

- Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease that becomes worse over time. There is currently no effective treatment for it. Researchers want to study the disease and learn new ways to treat it.

Objectives:

- To discover new pathways that are involved in pulmonary fibrosis. To develop new drugs that may be used to treat pulmonary fibrosis.

Eligibility:

• People at least 18 years old with IPF.
• Healthy volunteers at least 18 years old.

Design:

• Participants will be screened with medical history, questionnaire, and physical exam. They will have blood, lung, and walking tests and chest scans.
• All participants will have 1 study visit, including:
• Medical history and physical exam.
• Questions about their breathing.
• Blood tests.
• Breathing tests.
• Six-minute walk test.
• Pregnancy test.
• Chest x-ray (healthy volunteers) or chest CT scan (people with pulmonary fibrosis ).
• Small area of skin may be removed.
• Genetic tests of blood and skin samples. Participants will probably not be informed of any findings. Samples may be used to make stem cells for use in research. Participants may be contacted in the future to give consent for this research.
• Some participants will have repeat visits over many years, repeating many of the study tests.

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Fibrosis

Detailed Description

Idiopathic Pulmonary Fibrosis (IPF) is a chronic progressive disease that occurs primarily in older individuals, 55 to 75 years of age, with a median survival of approximately 3 years from time of diagnosis. At present, there are no effective treatments for patients with IPF. Levels of apolipoprotein A-I (apoA-I) have been found to be reduced in the lungs of patients with IPF, while administration of human apoA-I has been shown to reduce bleomycin-induced collagen deposition in a murine model. Here, we would like to assess whether apoA-I pathways modify lung cell biology in patients with IPF. This is a specimen procurement, clinical phenotyping and genotyping protocol that will assess whether holo-apoA-I and apolipoprotein A-I mimetic peptides, can attenuate key pathogenic manifestations of IPF, such as proliferation and extracellular matrix generation by pulmonary fibroblasts, which may serve as evidence to support future human clinical trials of apoA-I for the treatment of IPF. Furthermore, the identification of new apoA-I responsive genes and pathways that mediate fibroblast proliferation in IPF may provide insights into disease pathogenesis and identify new therapeutic targets. Lastly, if induced pluripotent stem (iPS) cells can be successfully shown to model responsiveness of lung cells to apoA-I therapy, then this approach may be expanded with the goal of providing a personalized medicine analysis that could in the future guide selection of the most effective therapy for individual patients.

• Study Type: Observational
• Enrollment (Actual): 63

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants will be enrolled at the NIH Clinical Center. IPF subjects will be recruited from the INOVA Fairfax Advanced Lung Disease Program and study procedures will be performed in the outpatient unit/day hospital at the NIH Clinical Center.@@@

Description

• INCLUSION CRITERIA:

Patient:

Males and females over the age of 18 with a diagnosis of IPF.

EXCLUSION CRITERIA:

Patient:

Female subjects who are pregnant or lactating

INCLUSION CRITERIA:

Normal Volunteer:

Males and females over the age of 18 without IPF.

EXCLUSION CRITERIA:

Normal Volunteer:

Female subjects who are pregnant or lactating

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
1; Participants will be enrolled at the NIH Clinical Center.
2; IPF subjects will be recruited from the INOVA Fairfax Advanced Lung Disease Program

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Specimen procurement, clinical phenotyping and genotyping that will assess whether holo-apoA-I and apolipoprotein A-I mimetic peptides, can attenuate key pathogenic manifestations of IPF	Therefore, we request participation of a maximum of 500 subjects (250 IPF patients and 250 non-IPF subjects) to ensure that we have a sufficient number of samples to achieve the goals of the study.	5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
The effects of stimulating cultures of primary pulmonary fibroblasts from IPF patients and subjects without IPF with apolipoprotein A-I will also be compared to the effects seen following stimulation with apolipoprotein E	5 years

Collaborators and Investigators

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Stewart J Levine, M.D., National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2015
• Primary Completion (Actual): November 2, 2016
• Study Completion (Actual): February 23, 2022

Study Registration Dates

• First Submitted: December 11, 2014
• First Submitted That Met QC Criteria: December 11, 2014
• First Posted (Estimated): December 12, 2014

Study Record Updates

• Last Update Posted (Estimated): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 8, 2024
• Last Verified: February 7, 2024

More Information

Terms related to this study

• Keywords: Natural History; Idiopathic Pulmonary Fibrosis; Apoliprotein A-1
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis
• Other Study ID Numbers: 150017; 15-H-0017

Drug and device information, study documents

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