CLAD Phenotype Specific Risk Factors and Mechanisms

Study Overview
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Brief Summary
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While many patients experience benefits from transplant, complications such as infections and lung rejection may affect long term survival and quality of life. In this study doctors are looking at a complication called Chronic Lung Allograft Dysfunction (CLAD). CLAD is thought to be chronic rejection of the lung by the immune system and is the leading cause of death after lung transplantation. The purpose of this study is to help doctors determine: why some people get CLAD and others do not how patients who get CLAD do after CLAD is diagnosed how CLAD may affect quality of life

Detailed Description
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This is an observational, prospective, multicenter study of newly transplanted adult, first lung transplant recipients that will collect longitudinal clinical data, patient reported quality of life (QOL) data, and serial biological samples to determine the risk factors, pathophysiology, and manifestations of restrictive chronic lung allograft dysfunction (RCLAD) and bronchiolitis obliterans syndrome (BOS). Anticipated participant accrual is within three years of study start-up. The total study duration is four years. Participants will be followed a minimum of 1 and a maximum of 4 years.

Official Title
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A Prospective Multicenter Observational Cohort Study to Define the Risks Factors, Mechanisms, and Manifestations of Chronic Lung Allograft Dysfunction (CLAD) Phenotypes (CTOT-20)

Conditions
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Lung Transplant, Post Lung Transplantation

Intervention / Treatment
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* Procedure: Blood Draw
* Procedure: Bronchoscopy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals who meet all of the following criteria are eligible for enrollment as study participants: Subject must be able to understand and provide written informed consent and -Must be ≥18 years of age at the time of written informed consent. Anticipated listing for lung transplantation OR within 45 days of having received a single or bilateral cadaveric donor lung transplant. - Enrollment must occur prior to the start of bronchoscopies eligible for research bronchoalveolar lavage (BAL) sampling. Undergoing first lung transplant operation. Transplant surgery to be performed or performed at enrolling center. Note: Concurrent participation in immune monitoring studies or interventional device trials are permitted. Exclusion Criteria: Individuals who meet any of the following criteria are not eligible for enrollment as study participants: Multi-organ recipient. Prior recipients of any solid organ transplant, including prior lung transplant. Prior or concurrent recipient of bone marrow transplant. HIV infection. Any condition which the investigators feel would make it unlikely for the recipient to complete follow up procedures or complete the study. Participation in an investigational drug trial at the time of enrollment visit.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Adult Lung Transplant Recipients<br>Adult lung transplant recipients undergoing lung transplant at each of the participating centers. | Procedure: Blood Draw<br> <br> * Other names: Venipuncture;Procedure: Bronchoscopy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from transplant to Restrictive Chronic Lung Allograft Dysfunction (RCLAD) or Bronchiolitis Obliterans Syndrome (BOS). | First occurrence of either phenotype. | 90 days post-transplant until study completion or participant withdrawal (up to 4 years post-transplant) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Longitudinal Quality of life (QOL) trajectory | As serially assessed by the 36-item Short Form Survey (SF-36) and the St. George's Respiratory Questionnaire (SGRQ) | Baseline until study completion or participant withdrawal (up to 4 years post-transplant) | 
| Mechanistic: Chemokine/cytokine Quantification of Type 1 and Type 17 immune profile proteins | Measured in the Bronchoalveolar lavage (BAL) supernatant.using standard Luminex and ELISA commercial assays | Baseline until study completion or participant withdrawal (up to 4 years post-transplant) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Lung Allograft Dysfunction (CLAD), Restrictive chronic lung allograft dysfunction (RCLAD), Bronchiolitis Obliterans Syndrome (BOS), CLAD risk factors, observational study