Multimodal prospective approach to understand acute and chronic lung transplant rejection

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

This project will see if blood tests, airway sampling, imaging, and genetic analyses can identify which adults who have had or are being evaluated for a lung transplant will develop antibody‑mediated rejection and later chronic graft dysfunction.

Quick facts

• Study type: Observational
• Enrollment: 100 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT07516379 on ClinicalTrials.gov

What this trial studies

This is a prospective, observational project recruiting adults who have undergone or are being evaluated for lung transplantation to the NIH Clinical Center. Participants will have clinic visits every 3–6 months for up to four years with blood draws, bronchoscopy with bronchoalveolar lavage, imaging, pulmonary function testing, and genetic/molecular profiling. The study will track donor-specific antibody (DSA) emergence and profile molecular changes that occur from DSA detection through acute antibody‑mediated rejection (AMR) and development of chronic lung allograft dysfunction (CLAD). Data aim to link clinical, imaging, and molecular signatures to timing and mechanisms of rejection.

Who should consider this trial

Good fit: Adults aged 18–75 who have had or are being evaluated for lung transplantation and who can comply with serial visits and procedures are ideal candidates.

Not a fit: Patients who are pregnant or breastfeeding, unable to undergo bronchoscopy or frequent follow-up, or unwilling to travel to the NIH Clinical Center are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the work could enable earlier, more personalized detection and treatment strategies to prevent antibody‑mediated rejection and slow progression to chronic graft dysfunction.

How similar studies have performed: Previous research has linked donor‑specific antibodies to lung transplant rejection, but comprehensive longitudinal molecular profiling to predict AMR and CLAD is relatively novel.

Eligibility criteria

* INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Stated willingness to comply with study procedures and availability for the duration of the study.
2. Male or female, aged 18 - 75 years of age.
3. Have undergone or being evaluated for lung transplantation.
4. 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

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Muhtadi H Alnababteh, M.D. — National Heart, Lung, and Blood Institute (NHLBI)
• Study coordinator: Andrew G Keel, C.R.N.P.

Conditions Lung Transplant; End Stage Lung Disease; Rejection