Multi-Omics-Based Prediction of Allograft Dysfunction After Lung Transplantation

NCT ID: NCT07243964

Last Updated: 2025-11-24

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 244 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-11-01
• Study Completion Date: 2030-03-01

Brief Summary

By establishing a prospective, multicenter lung transplantation clinical cohort, this study aims to systematically evaluate the utility of cfDNA fragmentomics, peripheral blood single-cell sequencing, and proteomics in monitoring and predicting graft dysfunction after lung transplantation, and to develop a multi-omics predictive model for early identification, dynamic monitoring, and mechanistic investigation of acute lung allograft dysfunction (ALAD) and chronic lung allograft dysfunction (CLAD).

Detailed Description

ALAD predominantly occurs in the early post-transplant period. This project aims to establish a systematic framework for monitoring and predicting post-lung transplant dysfunction, with a specific focus on acute lung allograft dysfunction (ALAD) and its progression to chronic lung allograft dysfunction (CLAD). We plan to conduct a prospective, multicenter clinical cohort study, longitudinally collecting peripheral blood and bronchoalveolar lavage fluid (BALF) samples from transplant recipients at various time points. By integrating multi-omics technologies-including cfDNA fragmentomics, peripheral blood single-cell sequencing, and proteomic mass spectrometry-with pulmonary function (FEV1) and clinicopathological data, we seek to delineate the dynamic landscape of post-lung transplant dysfunction. Compared to previous studies that relied on single indicators or one-time measurements, this project is distinguished by several key features: Firstly, the use of cfDNA fragmentomic characteristics to infer tissue origin, enabling highly specific detection of graft injury without requiring donor genotype information. Secondly, the integration of single-cell transcriptomics to comprehensively analyze the dynamics of peripheral immune cell subsets, providing a basis for early immunological warning of dysfunction. Thirdly, the application of proteomics to reveal expression levels, post-translational modifications, and protein-protein interactions in plasma samples. Fourthly, the construction of a multi-dimensional integrated model incorporating blood, BALF, and pulmonary function data, with the goal of establishing a generalizable early warning system. Through this research, we aim not only to enhance the early identification and intervention of ALAD but also to lay the foundation for elucidating the molecular mechanisms underlying CLAD development and exploring potential therapeutic targets.

Conditions

Lung Diseases

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

longitudinal changes in multi-omics profiling of peripheral blood

This study investigates the associations between longitudinal changes in multi-omics profiling of peripheral blood-including cell-free DNA, single-cell transcriptomics, proteomics, and metabolomics-and the development of acute lung allograft dysfunction(ALAD) and chronic lung allograft dysfunction(CLAD) in lung transplant recipients at various postoperative time points.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Recipients aged ≥18 years undergoing single or double lung transplantation;

2. Postoperative recipients capable of understanding and providing written informed consent, and willing to comply with scheduled follow-ups and sample collections as required by the study;

3. Postoperative recipients clinically assessed as stable and eligible for routine follow-up and hematological examinations;

4. Recipients able to undergo dynamic pulmonary function monitoring during follow-up;

5. No planned participation in other interventional trials during the study period that may impact immune function or pulmonary function;

6. Retransplant patients will be considered as a new transplant event and may be included in the analysis.

Exclusion Criteria

1. History of active malignancy or presence of untreated malignancy within 5 years prior to transplantation;

2. Presence of active systemic infection or significant immune rejection;

3. Female patients who are pregnant or lactating;

4. Any other condition deemed by the investigator to be inappropriate for inclusion .

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chang Chen

OTHER

Sponsor Role: lead

Responsible Party

Chang Chen

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Chang Chen, MD,PHD

Role: PRINCIPAL_INVESTIGATOR

Shanghai Pulmonary Hospital, Shanghai, China

Locations

Shanghai Pulmonary Hospital

Shanghai, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Junqi Wu

Role: CONTACT

wujunqi@tongji.edu.cn

+8615618977421

Facility Contacts

Junqi Wu

Role: primary

wujunqi@tongji.edu.cn

+8615618977421

Other Identifiers

L25-802

Identifier Type: -

Identifier Source: org_study_id