Characterization of Bronchiolitis-obliterans Syndrome (BOS) Following Lung Transplantation

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2009 by Hannover Medical School.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Hannover Medical School
ClinicalTrials.gov Identifier:
NCT00774449
First received: October 16, 2008
Last updated: July 19, 2011
Last verified: July 2009
  Purpose

Chronic organ dysfunction after lung transplantation (BOS) is the most common cause of death in long-term survivors after lung transplantation and refractory to most interventions. Early markers will be established in this project study to overcome the problem of disease recognition when impairment of graft function is already taken place. Long-term longitudinal monitoring in stable recipients of innovative markers of airway inflammation and ventilation and new imaging techniques will define different entities of chronic organ dysfunction after LTx. A database and specimen service unit for further projects will be created.

Hypothesis: This project will reveal new markers and imaging tools in recipients who develop BOS after lung transplantation. These tools will allow earlier diagnosis and more accurate monitoring of the disease process. Different patterns of the disease will be characterized.


Condition
Lung Transplantation
Bronchiolitis Obliterans Syndrome

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Characterization of Bronchiolitis-obliterans Syndrome (BOS) Following Lung Transplantation

Resource links provided by NLM:


Further study details as provided by Hannover Medical School:

Primary Outcome Measures:
  • Bronchiolitis obliterans Syndrom (BOS) [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Biospecimen Retention:   Samples Without DNA

bronchoalveolar lavage, transbronchial biopsies, blood samples


Estimated Enrollment: 261
Study Start Date: July 2009
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
1
individuals, who have undergone double (DLTx) or heart and lung transplantation (HLTx) at Hannover Medical School 6 months prior to inclusion

Detailed Description:

Chronic organ dysfunction of the lung allograft is the most common cause of death in lung transplant recipients after the first postoperative year and is a major cause of morbidity in the long-term care. It affects every second recipient surviving 5 years after transplantation (Boehler, Estenne 2003). Obliterative bronchiolitis (OB) is the histo-pathological process underlying chronic organ dysfunction after LTx. Bronchiolitis obliterans syndrome (BOS) is the clinical definition of chronic organ dysfunction following lung transplantation (LTx) and refers to a progressive obstructive ventilatory disorder. Staging is performed according to baseline values of forced expiratory volume after LTx (Estenne et al. 2001).

Excessive immunosuppression may be deleterious by increasing the risk of infection, thereby triggering innate and adaptive immunity. BOS is progressive in most of the cases with stabilisation in some. Different clinical entities are found according to time of onset, speed of decline in graft function (Jackson et al. 2002), ventilatory patterns, findings on imaging studies (Pakhale et al 2005, Choi et al 2003) and response to macrolides (Gerhardt et al. 2003). Exhaled biomarkers are promising markers of disease activity in pats with BOS (an Muylem 2007, Brugiere et al 2005) Alloimmune-independent and -dependent mechanisms produce injuries and inflammation of epithelial cells and subepithelial structures, leading to aberrant tissue repair (Nicod et al 2006). The triggering of innate immunity by various infections (especially respiratory viruses, Khalifah et al 2004) or chemical injuries (e.g. gastroesophageal reflux or aspiration, Palmer et al. 2000), may lead to the release of danger signals that are able to activate dendritic cells, a crucial link with adaptive immunity. Inflammation can also increase the expression and display of major histocompatibility alloantigens and thus favor the initiation of rejection episodes. The injuries evoke a proinflammatory response and cellular infiltration that leads to excessive fibroproliferation and results in matrix deposition and vascular remodelling. These phenomena may be limited in time and location or may be protracted. Reducing the risk of alloimmune-independent factors may be as important as treating acute episodes of lung rejection.

Newpotential therapeutic targets are emerging from the research performed on leukotriene receptors, chemokine receptors, and growth factors. Neutralizing these molecules may reduce the initial mononuclear and polynuclear infiltrates or the subsequent fibroproliferative process and the neovascular changes, feeding this process. (Nicod 2006). Macrolides are promising new agents which partially reverse loss of graft function in a subgroup of patients, which may change definition of BOS in the near future (Gerhardt et al 2003).

  Eligibility

Ages Eligible for Study:   18 Years to 68 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

individuals, who have undergone double (DLTx) or heart and lung transplantation (HLTx) at Hannover Medical School 6 months prior to inclusion

Criteria

Inclusion Criteria:

  • Individuals, who have undergone double (DLTx) or heart and lung transplantation (HLTx) at Hannover Medical School 6 months prior to inclusion
  • Ages: 18 to 68 Years
  • Gender: both
  • Stable graft function (FEV1 >90% baseline)

Exclusion Criteria:

  • Severe airway complications after surgery necessitating repeated intervention during the last 3 months
  • Need for supplemental oxygen at time of inclusion
  • Single lung (SLTx) and living lobar recipients
  • Established diagnosis of BOS at time of inclusion
  • Inability to undergo bodyphlethysmography e.g. due to persistent infection with multi-drug resistant bacteria (MRSA, VRE, Burkholderia Cepacia, Pandorea)
  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: NCT00774449

Contacts
Contact: Jens Gottlieb, MD +49-511-532 ext 3560 gottlieb.jens@mh-hannover.de

Locations
Germany
Department of Respiratory Medicine, Medizinische Hochschule Hannover Recruiting
Hannover, Germany, 30625
Contact: Jens Gottlieb, MD    +49-511-532 ext 3560    gottlieb.jens@mh-hannover.de   
Principal Investigator: Jens Gottlieb, MD         
Sponsors and Collaborators
Hannover Medical School
Investigators
Principal Investigator: Jens Gottlieb, MD Hannover Medical School
  More Information

No publications provided

Responsible Party: Dr. Jens Gottlieb, Hannover Medical School, Department of Respiratory Medicine
ClinicalTrials.gov Identifier: NCT00774449     History of Changes
Other Study ID Numbers: 5108
Study First Received: October 16, 2008
Last Updated: July 19, 2011
Health Authority: Germany: Ethics Commission

Keywords provided by Hannover Medical School:
lung transplantation
bronchiolitis obliterans syndrome
broncholaveolar lavage
high-resolution computertomography
quality of life

Additional relevant MeSH terms:
Bronchiolitis
Bronchiolitis Obliterans
Bronchitis
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Infections

ClinicalTrials.gov processed this record on August 21, 2014