Predictive Factors for Chronic Rejection in Lung Transplant Recipients: COLT Study (COLT)

Obliterative Bronchiolitis (OB) is the major cause of long-term lung allograft loss for patients with end stage pulmonary diseases like cystic fibrosis. Numerous cells and proteins are implicated in this process, which have never been studied prospectively in a multicentric longitudinal cohort. The aim of this study is to detect predictive risk factors of OB through a national multicentric cohort of 500 newly transplanted recipients (COLT). COLT will consist in a large database, associated with a recipient bio-collection, and specific projects using these resources. COLT will aggregate all the 11 French centres of pulmonary transplantation. Patient will be followed-up during 5 years. Blood samples will be obtained. Induced sputum, bronchoalveolar lavage fuid, exhaled breath condensate and trans bronchial biopsies will be also taken. T cells, known to be involved in chronic rejection will be studied, and genomic, microarray and proteomic approaches will be used to detect further predictive factors. A study on Circulating Endothelial Cells and Circulating Endothelial Progenitors is also realised from blood samples. COLT will prove molecular markers to be predictive of early OB, before the development of severe airway obstruction and will allow the identification of patients at high risk of OB. COLT will identify potential targets for future treatments of OB. This collaborative project makes research and clinical teams working together, and creates the conditions of a long term network, extendable to other laboratories with new projects and additional European transplant centres.

Study Overview

• Status: Unknown
• Conditions: Lung Transplantation; Chronic Rejection
• Intervention / Treatment: Other: Study of predictive factors

• Study Type: Interventional
• Enrollment (Actual): 700
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33604
    • CHU de Bordeaux
  • Grenoble, France, 38700
    • CHU de Grenoble
  • Le Plessis-Robinson, France, 92350
    • Centre Chirurgical Marie Lannelongue
  • Lyon, France, 69677
    • CHU de Lyon
  • Marseille, France, 13015
    • CHU de Marseille
  • Nantes, France, 44093
    • CHU Nantes
  • Paris, France, 75018
    • Hôpital Bichat
  • Paris, France, 75015
    • HEGP
  • Strasbourg, France, 67091
    • CHRU de Strasbourg
  • Suresnes, France, 92150
    • Hôpital Foch
  • Toulouse, France, 31059
    • CHU de Toulouse

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female adults aged ≥ 18 years
• who have signed an Inform Consent Form
• double or heart-lung transplant recipients

Exclusion Criteria:

• Pregnant or nursing women
• Patients with concomitant chronic inflammatory disease, independently of acute or chronic rejection or infection

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Identification of predictive factors for lung chronic rejection outcome in lung transplant recipients. This primary outcome will be evaluated at the end of the study.	8 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Evaluate the pertinence of a monitoring of lung chronic rejection based on the predictive factors identified in the study, in order to prevent this rejection. The secondary outcome measure will be evaluated at the end of the study.	8 years

Collaborators and Investigators

• Sponsor: Nantes University Hospital

Publications and helpful links

General Publications

• Durand M, Lacoste P, Danger R, Jacquemont L, Brosseau C, Durand E, Tilly G, Loy J, Foureau A, Royer PJ, Tissot A, Roux A, Reynaud-Gaubert M, Kessler R, Mussot S, Dromer C, Brugiere O, Mornex JF, Guillemain R, Claustre J, Degauque N, Magnan A, Brouard S; COLT and SysCLAD Consortia. High circulating CD4+CD25hiFOXP3+ T-cell sub-population early after lung transplantation is associated with development of bronchiolitis obliterans syndrome. J Heart Lung Transplant. 2018 Jun;37(6):770-781. doi: 10.1016/j.healun.2018.01.1306. Epub 2018 Mar 20.
• Benmerad M, Slama R, Botturi K, Claustre J, Roux A, Sage E, Reynaud-Gaubert M, Gomez C, Kessler R, Brugiere O, Mornex JF, Mussot S, Dahan M, Boussaud V, Danner-Boucher I, Dromer C, Knoop C, Auffray A, Lepeule J, Malherbe L, Meleux F, Nicod L, Magnan A, Pison C, Siroux V; SysCLAD consortium. Chronic effects of air pollution on lung function after lung transplantation in the Systems prediction of Chronic Lung Allograft Dysfunction (SysCLAD) study. Eur Respir J. 2017 Jan 18;49(1):1600206. doi: 10.1183/13993003.00206-2016. Print 2017 Jan.
• Pison C, Magnan A, Botturi K, Seve M, Brouard S, Marsland BJ, Ernst F, Paprotka T, Deplanche K, Fritz A, Siroux V, Boissel JP, Corris PA, Auffray C, Nicod LP; SysCLAD consortium. Prediction of chronic lung allograft dysfunction: a systems medicine challenge. Eur Respir J. 2014 Mar;43(3):689-93. doi: 10.1183/09031936.00161313. No abstract available.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Anticipated): September 1, 2017
• Study Completion (Anticipated): September 1, 2017

Study Registration Dates

• First Submitted: September 11, 2009
• First Submitted That Met QC Criteria: September 18, 2009
• First Posted (Estimate): September 21, 2009

Study Record Updates

• Last Update Posted (Estimate): May 12, 2015
• Last Update Submitted That Met QC Criteria: May 11, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Lung transplantation; Predictive factors; Obliterative bronchiolitis; Chronic lung rejection
• Other Study ID Numbers: BRD 09/1-F