Lung Allograft Rejection Gene Expression Observational (LARGO) Study

This study has been terminated.
(Restructuring and refocus of company.)
Sponsor:
Information provided by:
XDx
ClinicalTrials.gov Identifier:
NCT00751309
First received: September 10, 2008
Last updated: December 17, 2008
Last verified: December 2008
  Purpose

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.


Condition Intervention
Graft Rejection
Lung Disease
Other: Non-interventional

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Lung Allograft Rejection Gene Expression Observational (LARGO) Study

Resource links provided by NLM:


Further study details as provided by XDx:

Primary Outcome Measures:
  • 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. [ Time Frame: Scheduled clinic visit ] [ Designated as safety issue: No ]
  • Obliterative Bronchiolitis diagnosed pathologically by biopsy or by a progressive decline in pulmonary function tests consistent with a diagnosis of Bronchiolitis Obliterans Syndrome (BOS). [ Time Frame: Scheduled clinic visit ] [ Designated as safety issue: No ]
  • Allograft function as determined via pulmonary function tests. [ Time Frame: Scheduled clinic visit ] [ Designated as safety issue: No ]
  • The absence of histologic rejection and normal or unchanged allograft function. [ Time Frame: Scheduled clinic visit ] [ Designated as safety issue: No ]
  • Documented CMV infection by culture, histology, or PCR, and at least one clinical sign or symptom of infection. [ Time Frame: Scheduled clinic visit ] [ Designated as safety issue: No ]
  • Infections other than CMV, e.g. bacterial, other viral, and fungal infections. [ Time Frame: Scheduled clinic visit ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Rejection of mild to moderate histologic severity prompting augmentation of the patient's chronic immunosuppressive regimen. [ Time Frame: Scheduled clinic visit ] [ Designated as safety issue: No ]
  • Allograft dysfunction during the study period. [ Time Frame: Scheduled clinic visit ] [ Designated as safety issue: No ]
  • Rejection of mild to moderate severity with allograft dysfunction prompting plasmapheresis or a diagnosis of "humoral" rejection. [ Time Frame: Scheduled clinic visit ] [ Designated as safety issue: No ]
  • Lymphoproliferative disorder (aka post-transplant lymphoma). [ Time Frame: Scheduled clinic visit ] [ Designated as safety issue: No ]
  • Graft Failure or Retransplantation. [ Time Frame: Scheduled clinic visit ] [ Designated as safety issue: No ]
  • All cause mortality. [ Time Frame: Scheduled clinic visit ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

venous blood plasma


Enrollment: 2044
Study Start Date: April 2004
Estimated Study Completion Date: January 2009
Estimated Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
1
Lung and heart-lung transplanted subjects.
Other: Non-interventional
Post-transplantation observational study

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

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00751309

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

Additional Information:
No publications provided

Responsible Party: Kenneth C. Fang, MD, XDx, Inc.
ClinicalTrials.gov Identifier: NCT00751309     History of Changes
Other Study ID Numbers: LARGO
Study First Received: September 10, 2008
Last Updated: December 17, 2008
Health Authority: United States: Institutional Review Board
United Kingdom: Research Ethics Committee
Germany: Ethics Commission
Canada: Ethics Review Committee
Austria: Ethikkommission

Keywords provided by XDx:
allograft
rejection
biopsy
gene
expression
pulmonary
lung
transplant

Additional relevant MeSH terms:
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 18, 2014