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

NCT07516379 | Recruiting

• 2 other identifiers: 10002352002352-H
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

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. ...

Conditions

Rejection; End Stage Lung Disease; Lung Transplant

Keywords

Lung Transplant; Rejection

Outcome Measures

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

  3 years

Secondary Outcomes (3)

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

  3 years

• 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

Study Arms (2)

DSA-

Lung transplant patients who didn't develop donor specific antibodies

DSA+

Lung transplant patients who developed donor specific antibodies

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults with lung transplantation, progressive lung disease, or undergoing evaluation for lung transplantation. The population includes: (1) lung transplant recipients across the post-transplant spectrum (stable maintenance, acute rejection, infection, chronic allograft dysfunction), (2) patients with advanced lung disease being evaluated as transplant candidates, and (3) patients with progressive pulmonary disorders that may warrant lung transplant

You may qualify if:

• 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.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• \. Pregnancy or lactation

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead
• National Institutes of Health Clinical Center (CC): collaborator

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (4)

• Alnababteh M, Sun J, Meda R, Ponor L, Shah P, Mathew J, Kong H, Charya A, Helen Luikart RN, Aryal S, Nathan SD, Orens JB, Khush KK, Jang M, Agbor-Enoh S, Keller MB. Impact of donor specific antibodies on longitudinal lung function and baseline lung allograft dysfunction. J Heart Lung Transplant. 2025 Nov;44(11):1766-1773. doi: 10.1016/j.healun.2025.06.012. Epub 2025 Jun 26.

  PMID: 40581272 BACKGROUND

• Alnababteh M, Keller MB, Kong H, Phipps K, Namian J, Ponor L, Shah P, Mathews J, Andargie T, Park W, Orens JB, Aryal S, Nathan SD, Bush E, Redekar N, Hill T, Jang M, Tian X, Agbor-Enoh S. Early post-transplant recipient tissue injury predicts allograft function, rejection and survival in lung transplant recipients: evidence from cell-free DNA. Eur Respir J. 2026 Apr 16;67(4):2402537. doi: 10.1183/13993003.02537-2024. Print 2026 Apr.

  PMID: 40744691 BACKGROUND

• Keller MB, Newman D, Alnababteh M, Bon A, Ponor L, Shah P, Mathew J, Kong H, Andargie T, Park W, Charya A, Luikart H, Intrieri T, Aryal S, Nathan SD, Orens JB, Khush KK, Jang M, Agbor-Enoh S. Molecular criteria for pulmonary antibody-mediated rejection are associated with an increased risk of allograft failure. J Heart Lung Transplant. 2025 Oct;44(10):1535-1542. doi: 10.1016/j.healun.2025.03.015. Epub 2025 Mar 20.

  PMID: 40120999 BACKGROUND

• Agbor-Enoh S, Jackson AM, Tunc I, Berry GJ, Cochrane A, Grimm D, Davis A, Shah P, Brown AW, Wang Y, Timofte I, Shah P, Gorham S, Wylie J, Goodwin N, Jang MK, Marishta A, Bhatti K, Fideli U, Yang Y, Luikart H, Cao Z, Pirooznia M, Zhu J, Marboe C, Iacono A, Nathan SD, Orens J, Valantine HA, Khush K. Late manifestation of alloantibody-associated injury and clinical pulmonary antibody-mediated rejection: Evidence from cell-free DNA analysis. J Heart Lung Transplant. 2018 Jul;37(7):925-932. doi: 10.1016/j.healun.2018.01.1305. Epub 2018 Jan 31.

  PMID: 29500138 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Rejection, Psychology

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Study Officials

• Muhtadi H Alnababteh, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

CONTACT

(301) 648-5674; andrew.keel@nih.gov

Muhtadi H Alnababteh, M.D.

CONTACT

(301) 827-3272; muhtadi.alnababteh@nih.gov

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2026
• First Posted: April 8, 2026
• Study Start: May 11, 2026
• Primary Completion (Estimated): March 27, 2032
• Study Completion (Estimated): March 27, 2032
• Last Updated: July 22, 2026

Record last verified: 2026-07-20

Locations

US (1)