Lung Transplantation RejectionNCT00339209
Prospective Lung Transplant Database for Genetic Research
An observational study of Lung Transplantation Rejection, run by National Institute of Environmental Health Sciences (NIEHS) at 2 sites in United States.
Trial summary
This study will create a database of clinical and biological research for use in future studies, with information obtained from lung transplant recipients. The database will consist of genetic material and clinical outcomes to be used in future genotyping studies, that is, studies regarding the genetic makeup of… Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Lung Transplantation Rejection
- How many people
- 400 participants
- Where
- 2 sitesUnited States
- Study dates
- 23 Jun 2005to 13 Apr 2007
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients evaluated for lung transplant at Duke University Medical Center will be eligible for the study.
Who cannot join
None listed.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Duke University Medical Center
Durham, North Carolina, 27710
NIEHS, Research Triangle Park
Research Triangle Park, North Carolina, 27709
About this study
This study will create a database of clinical and biological research for use in future studies, with information obtained from lung transplant recipients. The database will consist of genetic material and clinical outcomes to be used in future genotyping studies, that is, studies regarding the genetic makeup of individuals. Lung transplantation has become an important option for patients with advanced lung disease. More than 10,000 patients have received them to date, and about 1,200 transplant operations are performed worldwide each year. Although short-term survival has continued to improve, the 5-year survival rate is less than 50 percent. Most post transplant deaths are directly or directly caused by chronic lung rejection, a condition of scarring that worsens lung function.
Patients evaluated for lung transplants at Duke University Medical Center may be eligible for this study.
Read more
For developing the database, a small amount of blood, about 3 tablespoons, will be collected from patients. Blood collection for the research will be done at the same time as blood is drawn for necessary tests. The blood cells and DNA (which contains genetic material) will be isolated for analysis. Patients' DNA samples collected will be identified by a code, and all other identifying information will be removed. Patients may be asked to donate additional blood samples after their lung transplant if researchers would like to reexamine their blood.
This study will not have a direct benefit for participants. However, during the study, if it is found that any patients have an inherited risk for a disease likely to cause early death if the disease is not treated, then the researchers will attempt to notify those patients. Overall, it is hoped that information gained during this study will help medical professionals to learn more about immune activation and to see how the reactivity of lung transplant patients changes over time. If specific genetic risks could be identified, it might lead to individualized treatments that work on the immune system. Short-term and long-term survival of lung transplant recipients may thus be improved.
Read the detailed description
Lung transplantation has emerged as a viable therapeutic option in the care of patients with advanced pulmonary parenchymal and pulmonary vascular disease. Currently, over 10,000 patients have received lung transplantation with approximately 1200 transplant operations performed worldwide each year. Short-term survival after lung transplantation has continued to improve since the widespread application of this procedure and one-year survival at most centers now approaches 80%. Unfortunately, long-term outcomes after lung transplantation are disappointing with five-year survival below 50%. Most posttransplant deaths are due directly or indirectly to the development of acute or chronic rejection. Acute rejection is defined by the presence of perivascular mononuclear inflammatory cells. Obliterative bronchiolitis (OB) describes fibrosis and obliteration of the small to medium size bronchioles, the histological manifestation of chronic lung rejection. Bronchiolitis obliterans syndrome (BOS) is thought to correlate with the development of histological OB when other causes of allograft dysfunction have been excluded. The diagnosis of OB is based primarily on a decline in spirometry with exclusion of alternative diagnoses with bronchoscopy and biopsy, i.e. development of clinical BOS. Since the introduction of BOS nomenclature, numerous studies have validated the clinical and prognostic importance of this syndrome and verified its correlation with histological OB.
Chronic rejection describes a histological pattern of fibrous obliteration of endothelial or epithelial structures in the allograft. A similar pattern of histological fibrosis is observed in all types of solid organ transplants (e.g., obliterative arteriopathy in heart transplant, BOS in lung transplant), and occurs despite the use of currently available, primarily T-cell based, immune suppression. The rates of chronic rejection vary considerably with the type of organ transplanted. By five years after transplantation histological fibrosis occurs in approximately 20% of kidney, 40% of heart and 60-80% of lung recipients. Thus, lung transplantation is characterized by an unusually high incidence of chronic graft rejection manifest as BOS.
Because of the high rate of acute and chronic lung transplant rejection, research designed to better correlate clinical outcomes with the genetic risks for rejection is critical to improving patient outcomes. We recently completed a study that demonstrated two single nucleotide polymorphisms (SNPs) Asp299Gly and Thr399Ile (polymorphisms of the human Toll 4 gene associated with endotoxin hyporesponsiveness) were associated with decreased acute rejection after lung transplantation.
We hypothesize that other SNPs associated with either increased or decreased innate or adaptive immune activation will be critical to determining the clinical outcome with regards to acute and chronic rejection after lung transplant. If specific genetic risks for rejection after transplant could be identified, this might lead to highly tailored immunosuppressive regimens and improved clinical outcomes.
- Conditions
- Lung Transplantation Rejection
- Keywords
- Genetic Polymorphisms, Acute Rejection, Bronchiolitis Obliterans Syndrome, Transplant Rejection, Innate Immunity, Lung Transplantation Rejection
- Medical subject headings
- Bronchiolitis Obliterans Syndrome
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2006 (estimated)
- Study start23 Jun 2005
- Study completion13 Apr 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lung Transplantation RejectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Enrolment
- 400 participants
Sponsor and investigators
- Lead sponsor
- National Institute of Environmental Health Sciences (NIEHS)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00339209
- Sponsor's protocol ID
- 999905184
- Other IDs
- 05-E-N184
- Status last verified
- 13 Apr 2007
- First submitted
- 19 Jun 2006
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Tazelaar HD, Yousem SA. The pathology of combined heart-lung transplantation: an autopsy study. Hum Pathol. 1988 Dec;19(12):1403-16. doi: 10.1016/s0046-8177(88)80233-8.
PubMed 3142814
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Lung Transplant Database for Genetic Research
- ClinicalTrials.gov ID
- NCT00339209
- Acronym / sponsor ID
- 999905184
- Conditions
- Lung Transplantation Rejection
- Keywords
- Genetic Polymorphisms, Acute Rejection, Bronchiolitis Obliterans Syndrome, Transplant Rejection, Innate Immunity, Lung Transplantation Rejection
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 400 participants
- Lead sponsor
- National Institute of Environmental Health Sciences (NIEHS)US National Institutes of Health
- Study start
- 23 Jun 2005
- Study completion
- 13 Apr 2007
- First posted
- 21 Jun 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will create a database of clinical and biological research for use in future studies, with information obtained from lung transplant recipients. The database will consist of genetic material and clinical outcomes to be used in future genotyping studies, that is, studies regarding the genetic makeup of individuals. Lung transplantation has become an important option for patients with advanced lung disease. More than 10,000 patients have received them to date, and about 1,200 transplant operations are performed worldwide each year. Although short-term survival has continued to improve, the 5-year survival rate is less than 50 percent. Most post transplant deaths are directly or directly caused by chronic lung rejection, a condition of scarring that worsens lung function.
Patients evaluated for lung transplants at Duke University Medical Center may be eligible for this study.
For developing the database, a small amount of blood, about 3 tablespoons, will be collected from patients. Blood collection for the research will be done at the same time as blood is drawn for necessary tests. The blood cells and DNA (which contains genetic material) will be isolated for analysis. Patients' DNA samples collected will be identified by a code, and all other identifying information will be removed. Patients may be asked to donate additional blood samples after their lung transplant if researchers would like to reexamine their blood.
This study will not have a direct benefit for participants. However, during the study, if it is found that any patients have an inherited risk for a disease likely to cause early death if the disease is not treated, then the researchers will attempt to notify those patients. Overall, it is hoped that information gained during this study will help medical professionals to learn more about immune activation and to see how the reactivity of lung transplant patients changes over time. If specific genetic risks could be identified, it might lead to individualized treatments that work on the immune system. Short-term and long-term survival of lung transplant recipients may thus be improved.
Detailed description
Lung transplantation has emerged as a viable therapeutic option in the care of patients with advanced pulmonary parenchymal and pulmonary vascular disease. Currently, over 10,000 patients have received lung transplantation with approximately 1200 transplant operations performed worldwide each year. Short-term survival after lung transplantation has continued to improve since the widespread application of this procedure and one-year survival at most centers now approaches 80%. Unfortunately, long-term outcomes after lung transplantation are disappointing with five-year survival below 50%. Most posttransplant deaths are due directly or indirectly to the development of acute or chronic rejection. Acute rejection is defined by the presence of perivascular mononuclear inflammatory cells. Obliterative bronchiolitis (OB) describes fibrosis and obliteration of the small to medium size bronchioles, the histological manifestation of chronic lung rejection. Bronchiolitis obliterans syndrome (BOS) is thought to correlate with the development of histological OB when other causes of allograft dysfunction have been excluded. The diagnosis of OB is based primarily on a decline in spirometry with exclusion of alternative diagnoses with bronchoscopy and biopsy, i.e. development of clinical BOS. Since the introduction of BOS nomenclature, numerous studies have validated the clinical and prognostic importance of this syndrome and verified its correlation with histological OB.
Chronic rejection describes a histological pattern of fibrous obliteration of endothelial or epithelial structures in the allograft. A similar pattern of histological fibrosis is observed in all types of solid organ transplants (e.g., obliterative arteriopathy in heart transplant, BOS in lung transplant), and occurs despite the use of currently available, primarily T-cell based, immune suppression. The rates of chronic rejection vary considerably with the type of organ transplanted. By five years after transplantation histological fibrosis occurs in approximately 20% of kidney, 40% of heart and 60-80% of lung recipients. Thus, lung transplantation is characterized by an unusually high incidence of chronic graft rejection manifest as BOS.
Because of the high rate of acute and chronic lung transplant rejection, research designed to better correlate clinical outcomes with the genetic risks for rejection is critical to improving patient outcomes. We recently completed a study that demonstrated two single nucleotide polymorphisms (SNPs) Asp299Gly and Thr399Ile (polymorphisms of the human Toll 4 gene associated with endotoxin hyporesponsiveness) were associated with decreased acute rejection after lung transplantation.
We hypothesize that other SNPs associated with either increased or decreased innate or adaptive immune activation will be critical to determining the clinical outcome with regards to acute and chronic rejection after lung transplant. If specific genetic risks for rejection after transplant could be identified, this might lead to highly tailored immunosuppressive regimens and improved clinical outcomes.
Study design
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients evaluated for lung transplant at Duke University Medical Center will be eligible for the study.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 3142814Tazelaar HD, Yousem SA. The pathology of combined heart-lung transplantation: an autopsy study. Hum Pathol. 1988 Dec;19(12):1403-16. doi: 10.1016/s0046-8177(88)80233-8.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Lung Transplantation Rejection, run by National Institute of Environmental Health Sciences (NIEHS) at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00339209, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.