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Study on Systemic and Airway Biomarkers in Haemopoietic Stem Cell Transplantation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00956358
Recruitment Status : Completed
First Posted : August 11, 2009
Last Update Posted : May 12, 2016
Information provided by (Responsible Party):
James Chung-Man HO, The University of Hong Kong

Tracking Information
First Submitted Date August 9, 2009
First Posted Date August 11, 2009
Last Update Posted Date May 12, 2016
Study Start Date March 2009
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: August 10, 2009)
Lung function indices [ Time Frame: Every 3 months until either 18 months post-HSCT or diagnosis of BOS ]
Original Primary Outcome Measures Same as current
Change History Complete list of historical versions of study NCT00956358 on Archive Site
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title Study on Systemic and Airway Biomarkers in Haemopoietic Stem Cell Transplantation
Official Title Study on Systemic and Airway Cytokines and Oxidative Stress in Patients Undergoing Haemopoietic Stem Cell Transplantation (HSCT)
Brief Summary

Haemopoietic stem cell transplantation (HSCT) has become a major life-saving treatment for many haematological conditions, mostly malignancies.

However, there are lots of potential complications that hinder the long-term success of HSCT, in which bronchiolitis obliterans syndrome (BOS) is one of such serious complications. Basically, BOS represents a form of graft-versus-host immunological damage of small airways (bronchioles), leading to progressive narrowing of small airways and thus obstructive lung function abnormalities. With progressive loss of lung function in BOS, patients after HSCT can be complicated by intractable respiratory failure that results in mortality. Up until now, there is still no reliable way to accurately predict or detect BOS early to allow pharmacological interventions.

Therefore there is intense interest in the search for biomarkers that can help to predict the occurrence of BOS after HSCT. Apart from biomarkers (e.g., cytokines) in blood, there has been recent development in the sampling of airway lining fluid by a non-invasive method, i.e., collection of exhaled breath condensate (EBC). In airway diseases such as asthma or chronic obstructive pulmonary disease, EBC has been found to have various cytokines which can serve as potential biomarkers of disease activity. Since BOS is largely a small airway disease, it becomes logical to investigate the profile of biomarkers in EBC as predictors for BOS after HSCT.

Therefore this study has been designed to look into the role of biomarkers in blood and EBC in early detection of BOS after HSCT.

Detailed Description

Haemopoietic stem cell transplantation (HSCT) has revolutionized the treatment of both haematological and perhaps some solid malignancies. However, despite recent technological advancements, HSCT is still associated with significant mortality and morbidities.

Apart from various infective complications in early stage post-HSCT, bronchiolitis obliterans syndrome (BOS) has been a well-known late complication that can result in high mortality. It has been mostly associated with those who develop chronic graft-versus-host disease after allogeneic HSCT. Clinically, the diagnosis of BOS is largely based on demonstration of obstructive lung function abnormalities and air-trapping in computed tomography scan of thorax. Pathologically, bronchiolitis obliterans is characterized by both inflammatory and fibrotic reactions in the small bronchioles leading to subsequent obliteration. Upon diagnosis of BOS post-HSCT, inhaled corticosteroid (with or without bronchodilators) is commonly prescribed as anti-inflammatory agent, though with undocumented clinical efficacy. Unfortunately, there is still a lack of reliable biomarkers that can predict or allow early detection of BOS, preferably in the early and potentially reversible stage of development of BOS.

Apart from measuring circulating biomarkers in blood, exhaled breath condensate (EBC) has recently emerged as a non-invasive sampling method for real-time analysis and evaluation of oxidative stress biomarkers in the lower respiratory tract airways, especially in various lung diseases including asthma, chronic obstructive pulmonary disease, and lung cancer. As bronchiolitis obliterans is predominantly a disease of the small bronchioles, it is highly likely to be associated with changes in various inflammatory and oxidative stress biomarkers in EBC. However, the role of measuring EBC biomarkers in predicting the occurrence of BOS after HSCT has not been studied. Therefore, the current study aims to evaluate the temporal changes of various oxidative stress biomarkers and cytokines in EBC and blood in patients with haematological conditions who undergo allogeneic HSCT, with regard to the subsequent development of BOS.

Study Type Observational
Study Design Observational Model: Case Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Plasma, buffy coat, red blood cell and exhaled breath condensate samples.
Sampling Method Non-Probability Sample
Study Population Haematological conditions requiring HSCT and healthy HSCT donors will be identified from Bone Marrow Transplatation (BMT) Unit and post-HSCT patients with BOS will be identified from Respiratory Medicine clinics at Queen Mary Hospital.
Condition Hematological Diseases
Intervention Not Provided
Study Groups/Cohorts
  • Pre-HSCT
    Haematological conditions requiring haemopoietic stem cell transplantation
  • Post-HSCT with BOS
    Occurence of bronchiolitis obliterans syndrome after haemopoietic stem cell transplantation
  • Control
    Healthy HSCT donors
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: May 11, 2016)
Original Estimated Enrollment
 (submitted: August 10, 2009)
Actual Study Completion Date December 2015
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Haematological conditions requiring HSCT (either autologous or allogeneic with sibling donor), post-HSCT BOS, or healthy HSCT donors
  • Life expectancy > 12 weeks

Exclusion Criteria:

  • Respiratory failure requiring use of supplemental oxygen therapy
  • Known airway diseases including asthma, chronic obstructive pulmonary disease and bronchiectasis
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Hong Kong
Removed Location Countries  
Administrative Information
NCT Number NCT00956358
Other Study ID Numbers UW 09-107
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party James Chung-Man HO, The University of Hong Kong
Study Sponsor The University of Hong Kong
Collaborators Not Provided
Principal Investigator: Chung-man James Ho The University of Hong Kong
PRS Account The University of Hong Kong
Verification Date May 2016