Lung TransplantNCT07516379
GRAfT 2.0. A Multimodal Prospective Approach to Define the Mechanisms and Clinical Features of Acute and Chronic Rejection in Lung Transplantation
An observational study of Lung Transplant and End Stage Lung Disease, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Lung Transplant, End Stage Lung Disease, Rejection
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 11 May 2026to 27 Mar 2032
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Who may be able to join
- 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.
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- 1. Pregnancy or lactation
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
NIH Clinical Center Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
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.
Read more
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.
...
Read the 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:
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
- Conditions
- Lung Transplant, End Stage Lung Disease, Rejection
- Keywords
- Lung Transplant, Rejection
- Medical subject headings
- Rejection, Psychology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| DSA- | Lung transplant patients who didn't develop donor specific antibodies | |
| DSA+ | Lung transplant patients who developed donor specific antibodies |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 3 years
Secondary outcomes (3)
Multi-omic molecular differences between participants who progress to CLAD (CLAD+), and no CLAD (CLAD-)
Measured: 3 years
Imaging findings differences (low dose CT, MRI, Confocal Microscopy) between (DSA+/AMR+), (DSA+/AMR-), and DSA- groups.
Measured: 3 years
Imaging findings differences (CT, MRI, Confocal Microscopy): Between CLAD+, and CLAD- participants
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2026
- Study start11 May 2026
- Primary completion27 Mar 2032 (estimated)
- Study completion27 Mar 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Lung TransplantStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- National Institutes of Health Clinical Center (CC)
- Responsible party
- Sponsor
- Investigators
- Muhtadi H Alnababteh, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07516379
- Sponsor's protocol ID
- 10002352
- Other IDs
- 002352-H
- Status last verified
- 20 Jul 2026
- First submitted
- 6 Apr 2026
- Last updated
- 22 Jul 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: IPD sharing plan will be determined upon study completion, contingent on appropriate de-identification methods for longitudinal transplant data and compliance with NIH data sharing policy.
Publications
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.
PubMed 40581272Alnababteh 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.
PubMed 40744691Keller 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.
PubMed 40120999Agbor-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.
PubMed 29500138
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- GRAfT 2.0. A Multimodal Prospective Approach to Define the Mechanisms and Clinical Features of Acute and Chronic Rejection in Lung Transplantation
- ClinicalTrials.gov ID
- NCT07516379
- Acronym / sponsor ID
- 10002352
- Conditions
- Lung Transplant, End Stage Lung Disease, Rejection
- Keywords
- Lung Transplant, Rejection
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Collaborators
- National Institutes of Health Clinical Center (CC)
- Study start
- 11 May 2026 (actual)
- Primary completion
- 27 Mar 2032 (estimated)
- Study completion
- 27 Mar 2032 (estimated)
- First posted
- 8 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
...
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:
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
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DSA- | – | –Lung transplant patients who didn't develop donor specific antibodies |
| DSA+ | – | –Lung transplant patients who developed donor specific antibodies |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (2 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- 1. Pregnancy or lactation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
3 secondary outcomes
Multi-omic molecular differences between participants who progress to CLAD (CLAD+), and no CLAD (CLAD-)
Time frame: 3 years
Imaging findings differences (low dose CT, MRI, Confocal Microscopy) between (DSA+/AMR+), (DSA+/AMR-), and DSA- groups.
Time frame: 3 years
Imaging findings differences (CT, MRI, Confocal Microscopy): Between CLAD+, and CLAD- participants
Time frame: 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2026.
- Background: PubMed 40581272Alnababteh 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.
- Background: PubMed 40744691Alnababteh 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.
- Background: PubMed 40120999Keller 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.
- Background: PubMed 29500138Agbor-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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. IPD sharing plan will be determined upon study completion, contingent on appropriate de-identification methods for longitudinal transplant data and compliance with NIH data sharing policy.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Muhtadi H Alnababteh, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Lung Transplant and End Stage Lung Disease, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Andrew G Keel, C.R.N.P. ((301) 648-5674, andrew.keel@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07516379, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2026.