Lung Allograft Rejection Gene Expression Observational (LARGO) Study (LARGO)

The objective of the LARGO Study protocol is to collect peripheral blood samples, select associated lung biopsy pathology slides, and clinical data from lung transplant recipients to perform molecular analyses in association with the study endpoints. The primary objective is to use gene expression profiling of peripheral blood mononuclear cells to differentiate between the absence and presence of acute cellular rejection. The secondary objectives are to use other genomic and proteomic technologies to analyze RNA and protein in blood samples in relation to related clinical conditions. The overall goal is to apply novel molecular insights in the development of non-invasive molecular diagnostic tests for lung transplantation.

Study Overview

• Status: Terminated
• Conditions: Lung Disease; Graft Rejection
• Intervention / Treatment: Other: Non-interventional

Detailed Description

LARGO is a prospective, multi-center, international observational study with participating centers in the United States, Canada and Europe. The target enrollment for study completion is 2,100 subjects.

At each study visit, blood specimens are collected from subjects, processed and stored in the sample archive, with corresponding patient information entered into the clinical database. The analysis plan for each study objective includes a defined sample selection protocol that stipulates the inclusion and exclusion criteria for both patients and samples, and also the required number of blood specimens for the molecular analyses to achieve statistical significance.

The diagnosis and treatment of acute cellular rejection remains a clinical management priority that is currently based on transbronchial biopsy. Gene expression profiling is a technology based on molecular biology that measures changes in the RNA levels of different genes expressed by circulating mononuclear cells in the peripheral blood. A key goal of the project is to use gene expression profiling to differentiate between the absence and presence of lung allograft acute cellular rejection, with the aim of using this novel information to develop a non-invasive diagnostic testing alternative.

• Study Type: Observational
• Enrollment (Actual): 2044

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medizinische Universitat Wien
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Hospital For Sick Children
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
• Germany
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
• United Kingdom
  • Newcastle upon Tyne
    • High Heaton, Newcastle upon Tyne, United Kingdom, NE7 7DN
      • Freeman Hospital
• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Division of Pulmonary and Critical Care
    • San Francisco, California, United States, 94117
      • University of California, San Francisco
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Transplant Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health Systems
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • St. Louis, Missouri, United States, 63110
      • St. Louis Children's Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia University College of Physicians and Surgeons
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15261
      • University of Pittsburgh
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University Hospital and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Lung and heart-lung transplant recipients who will undergo transbronchial biopsy.

Description

Inclusion Criteria:

• Lung and heart-lung transplant recipients who consent to participate and have transbronchial biopsy at the enrolling center during the study period

Exclusion Criteria:

• None

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
1; Lung and heart-lung transplanted subjects.	Other: Non-interventional; Post-transplantation observational study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rejection episodes of at least moderate histologic grade which resulted in treatment of the patient with additional corticosteroids, anti-T cell antibodies, or total lymphoid irradiation.	Scheduled clinic visit
Obliterative Bronchiolitis diagnosed pathologically by biopsy or by a progressive decline in pulmonary function tests consistent with a diagnosis of Bronchiolitis Obliterans Syndrome (BOS).	Scheduled clinic visit
Allograft function as determined via pulmonary function tests.	Scheduled clinic visit
The absence of histologic rejection and normal or unchanged allograft function.	Scheduled clinic visit
Documented CMV infection by culture, histology, or PCR, and at least one clinical sign or symptom of infection.	Scheduled clinic visit
Infections other than CMV, e.g. bacterial, other viral, and fungal infections.	Scheduled clinic visit

Secondary Outcome Measures

Outcome Measure	Time Frame
Rejection of mild to moderate histologic severity prompting augmentation of the patient's chronic immunosuppressive regimen.	Scheduled clinic visit
Allograft dysfunction during the study period.	Scheduled clinic visit
Rejection of mild to moderate severity with allograft dysfunction prompting plasmapheresis or a diagnosis of "humoral" rejection.	Scheduled clinic visit
Lymphoproliferative disorder (aka post-transplant lymphoma).	Scheduled clinic visit
Graft Failure or Retransplantation.	Scheduled clinic visit
All cause mortality.	Scheduled clinic visit

Collaborators and Investigators

• Sponsor: XDx
• Investigators: Study Director: Kenneth C. Fang, MD, XDx, Inc.

Publications and helpful links

Helpful Links

• Information on molecular expression testing
• Sponsor's website

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (Anticipated): January 1, 2009
• Study Completion (Anticipated): January 1, 2009

Study Registration Dates

• First Submitted: September 10, 2008
• First Submitted That Met QC Criteria: September 10, 2008
• First Posted (Estimate): September 11, 2008

Study Record Updates

• Last Update Posted (Estimate): December 18, 2008
• Last Update Submitted That Met QC Criteria: December 17, 2008
• Last Verified: December 1, 2008

More Information

Terms related to this study

• Keywords: transplant; lung; allograft; rejection; biopsy; pulmonary; gene; expression
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases
• Other Study ID Numbers: LARGO