GRAfT 2.0. A Multimodal Prospective Approach to Define the Mechanisms and Clinical Features of Acute and Chronic Rejection in Lung Transplantation
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- Multi-omic molecular differences between DSA+ participants who progress to AMR (DSA+/AMR+), and DSA+ participants who do not progress to AMR (DSA+/AMR-), and DSA- participants
Study Overview
Brief Summary
Background:
Lung transplants can save lives, but the procedure has risks. Some people develop donor-specific antibodies (DSA) after the procedure-that is, their bodies create proteins that treat the new lungs as foreign and mount an immune response against them. This is called rejection. But not everyone who has a transplant develops DSA, and not everyone who has DSA develops rejection. Researchers want to understand why.
Objective:
To collect data to try to find out why some people develop rejection after lung transplants while others do not.
Eligibility:
People aged 18 to 75 years who have progressive lung disease or undergone or may undergo a lung transplant.
Design:
Participants will have clinic visits every 3 to 6 months for up to 4 years. Some visits might require an overnight stay.
Each visit will include multiple tests and procedures:
Physical exam with blood and urine tests. Some blood will be used for genetic testing.
Imaging scans. Participants will have 2 types of scan to get images of their lungs. For one, they will have a contrast agent given through a tube inserted into a vein.
Six-minute walk test. Participants will walk back and forth in a hallway at their own pace. Researchers will check on how their body responds.
Lung function test. Participants will breathe into a tube connected to a machine.
Two other tests are optional:
Bronchoscopy with washings (lavage). A long tube with a light will be threaded down through the participant s nose or mouth and into their lungs.
Endomicroscopy. During the bronchoscopy a tiny camera may be used to take pictures inside the lungs.
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Detailed Description
Study Description:
Our hypothesis is that lung transplant recipients with donor-specific antibodies (DSA) who develop AMR (DSA+/AMR+) exhibit distinct molecular mechanisms compared to DSA+/AMR- and DSA-recipients.
This study will recruit patients with progressive lung disease or who are being evaluated or have received a lung transplant to the NIH Clinical Center to investigate these differences. Participants will undergo blood draws, bronchoscopy with bronchoalveolar lavage, imaging and other diagnostic testing. After the initial visit, participants will continue routine care in their transplant programs with multiple planned NIH follow-up visits for blood draw and testing/sampling. The primary goal of this proposal is to profile the molecular changes from DSA detection to the development of acute rejection (AR) and subsequent development of chronic lung allograft dysfunction (CLAD).
Secondary goals of the study are to profile changes in pulmonary function testing, pulmonary imaging, surveillance bronchoscopy, and advanced bronchoscopy measures that coincide with the molecular changes. The dynamic assessment is poised to identify actionable timing and molecular targets to preemptively treat patients before AMR develops and to halt progression to CLAD.
Objectives:
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •INCLUSION CRITERIA:
- •In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- •Stated willingness to comply with study procedures and availability for the duration of the study.
- •Male or female, aged 18 - 75 years of age.
- •Have progressive lung disease or undergone or being evaluated for lung transplantation.
- •Ability of subjects to understand the informed consent document.
Exclusion Criteria
- •An individual who meets any of the following criteria will be excluded from participation in this study:
- •1. Pregnancy or lactation
Arms & Interventions
DSA-
Lung transplant patients who didn't develop donor specific antibodies
DSA+
Lung transplant patients who developed donor specific antibodies
Outcomes
Primary Outcomes
Multi-omic molecular differences between DSA+ participants who progress to AMR (DSA+/AMR+), and DSA+ participants who do not progress to AMR (DSA+/AMR-), and DSA- participants
Time Frame: 3 years
Secondary Outcomes
- Imaging findings differences (low dose CT, MRI, Confocal Microscopy) between (DSA+/AMR+), (DSA+/AMR-), and DSA- groups.(3 years)
- Imaging findings differences (CT, MRI, Confocal Microscopy): Between CLAD+, and CLAD- participants(3 years)
- Multi-omic molecular differences between participants who progress to CLAD (CLAD+), and no CLAD (CLAD-)(3 years)