Clinical trial NCT00751309: Lung Allograft Rejection Gene Expression Observational (LARGO) Study
Official title: Lung Allograft Rejection Gene Expression Observational (LARGO) Study
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Graft Rejection
Lung Disease
Keywords: allograft
rejection
biopsy
gene
expression
pulmonary
lung
transplant
Lead sponsor: XDx
Sponsor class: INDUSTRY
First posted: 2008-09-11
Enrollment: 2044
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Lung and heart-lung transplant recipients who will undergo transbronchial biopsy.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: Scheduled clinic visit
measure: Obliterative Bronchiolitis diagnosed pathologically by biopsy or by a progressive decline in pulmonary function tests consistent with a diagnosis of Bronchiolitis Obliterans Syndrome (BOS).
timeFrame: Scheduled clinic visit
measure: Allograft function as determined via pulmonary function tests.
timeFrame: Scheduled clinic visit
measure: The absence of histologic rejection and normal or unchanged allograft function.
timeFrame: Scheduled clinic visit
measure: Documented CMV infection by culture, histology, or PCR, and at least one clinical sign or symptom of infection.
timeFrame: Scheduled clinic visit
measure: Infections other than CMV, e.g. bacterial, other viral, and fungal infections.
timeFrame: Scheduled clinic visit
Secondary outcomes:
measure: Rejection of mild to moderate histologic severity prompting augmentation of the patient's chronic immunosuppressive regimen.
timeFrame: Scheduled clinic visit
measure: Allograft dysfunction during the study period.
timeFrame: Scheduled clinic visit
measure: Rejection of mild to moderate severity with allograft dysfunction prompting plasmapheresis or a diagnosis of "humoral" rejection.
timeFrame: Scheduled clinic visit
measure: Lymphoproliferative disorder (aka post-transplant lymphoma).
timeFrame: Scheduled clinic visit
measure: Graft Failure or Retransplantation.
timeFrame: Scheduled clinic visit
measure: All cause mortality.
timeFrame: Scheduled clinic visit
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Division of Pulmonary and Critical Care
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic Transplant Center
state: Florida
city: Ann Arbor
country: United States
facility: University of Michigan Health Systems
state: Michigan
city: St. Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Columbia University College of Physicians and Surgeons
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Madison
country: United States
facility: University Hospital and Clinics
state: Wisconsin
city: Vienna
country: Austria
facility: Medizinische Universität Wien
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: High Heaton
country: United Kingdom
facility: Freeman Hospital
state: Newcastle upon Tyne
Study officials:
affiliation: XDx, Inc.
name: Kenneth C. Fang, MD
role: STUDY_DIRECTOR
References: