CLAD Phenotype Specific Risk Factors and Mechanisms

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

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

Study Overview

• Status: Completed
• Conditions: Lung Transplant; Post Lung Transplantation
• Intervention / Treatment: Procedure: Bronchoscopy; Procedure: Blood Draw

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 884

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • University of Toronto
• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Adult lung transplant recipients undergoing lung transplant at each of the participating centers.

Description

Inclusion Criteria:

Individuals who meet all of the following criteria are eligible for enrollment as study participants:

1. 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.

2. 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.

3. Undergoing first lung transplant operation.

4. 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:

1. Multi-organ recipient.
2. Prior recipients of any solid organ transplant, including prior lung transplant.
3. Prior or concurrent recipient of bone marrow transplant.
4. HIV infection.
5. Any condition which the investigators feel would make it unlikely for the recipient to complete follow up procedures or complete the study.
6. Participation in an investigational drug trial at the time of enrollment visit.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Adult Lung Transplant Recipients; Adult lung transplant recipients undergoing lung transplant at each of the participating centers.	Procedure: Bronchoscopy; Procedure: Blood Draw; Other Names: Phlebotomy; Venipuncture

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Clinical Trials in Organ Transplantation
• Investigators: Study Chair: John Belperio, MD, University of California, Los Angeles

Publications and helpful links

Helpful Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)
• Clinical Trials in Organ Transplantation (CTOT)

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2015
• Primary Completion (Actual): November 30, 2019
• Study Completion (Actual): November 30, 2019

Study Registration Dates

• First Submitted: December 14, 2015
• First Submitted That Met QC Criteria: December 14, 2015
• First Posted (Estimate): December 16, 2015

Study Record Updates

• Last Update Posted (Actual): December 17, 2019
• Last Update Submitted That Met QC Criteria: December 16, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: observational study; Chronic Lung Allograft Dysfunction (CLAD); Restrictive chronic lung allograft dysfunction (RCLAD); Bronchiolitis Obliterans Syndrome (BOS); CLAD risk factors
• Other Study ID Numbers: DAIT CTOT-20