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NCT Number: NCT07516379

GRAfT 2.0. A Multimodal Prospective Approach to Define the Mechanisms and Clinical Features of Acute and Chronic Rejection in Lung Transplantation

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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Key information

Conditions

Lung Transplant Behavior End Stage Lung Disease Rejection Rejection, Psychology Social Behavior

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Observational

Primary location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location status: Recruiting

Location contact

NIH Clinical Center Office of Patient Recruitment (OPR)

CONTACT

[email protected]

800-411-1222 ext. TTY dial 711

About this study

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:

Primary Objective:

-To identify molecular pathways associated with development of AMR from DSA

Secondary Objectives:

  • To identify clinical subtypes (endotypes) of AMR
  • To identify molecular and clinical pathways associated with development of CLAD from AMR

Endpoints:

Primary Endpoint:

-Multi-omic molecular differences between DSA+ participants who progress to AMR (DSA+/AMR+), DSA+ participants who do not progress to AMR (DSA+/AMR-), and DSA- participants.

Secondary Endpoints:

  • Multi-omic molecular differences between participants who progress to CLAD (CLAD+), and no CLAD (CLAD-)
  • Physiological changes (PFT, 6MWT) between (DSA+/AMR+), (DSA+/AMR-), and DSA- groups.
  • Physiological changes (PFT, 6MWT): Between CLAD+, and CLAD- participants
  • Imaging findings differences (low dose CT, MRI, Confocal Microscopy) between (DSA+/AMR+), (DSA+/AMR-), and DSAgroups.
  • Imaging findings differences (CT, MRI, Confocal Microscopy): Between CLAD+, and CLAD- participants

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

  • 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:

  • Pregnancy or lactation

Treatment and study plan

Primary outcomes

  1. 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

  1. Multi-omic molecular differences between participants who progress to CLAD (CLAD+), and no CLAD (CLAD-)

    Time frame: 3 years

  2. Imaging findings differences (low dose CT, MRI, Confocal Microscopy) between (DSA+/AMR+), (DSA+/AMR-), and DSA- groups.

    Time frame: 3 years

  3. Imaging findings differences (CT, MRI, Confocal Microscopy): Between CLAD+, and CLAD- participants

    Time frame: 3 years

Study contacts

Contact information is provided by the study sponsor or research team.

Andrew G Keel, C.R.N.P.

CONTACT

[email protected]

(301) 648-5674

Muhtadi H Alnababteh, M.D.

CONTACT

[email protected]

(301) 827-3272

Sponsors and collaborators

Lead sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Nih

Collaborators

  • National Institutes of Health Clinical Center (CC)

Registry information

Important dates

Study start
2026
Primary completion
2032
Study completion
2032
First posted
Apr 8, 2026
Registry last updated
Jul 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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