Organ Transplant RejectionCSMCDTITAROTNCT03255265
Clinical Study of Microchimerism and cfDNA as Biomarkers for Acute Rejection After Organ Transplantation
An observational study of Organ Transplant Rejection, run by Fuzhou General Hospital at 1 site in China.
Trial summary
Organ transplantation has become an effective therapy for patients with end-stage organ failure at present. Rejection is still the most common cause of early dysfunction after organ transplantation. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Organ Transplant Rejection
- How many people
- 950 participants
- Where
- 1 siteChina
- Study dates
- 1 Mar 2017to 31 Dec 2021
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: aged above 18 years old single organ transplant patients (first or again); Guardian or self-signed informed consent.
Who may be able to join
- Single-organ transplant recipients aged above 18 years old Recipients of re-do organ transplants
- Recipients with no systemic acute or chronic infections, infectious diseases;
- Recipients with no severe systemic diseases and/or spiritual system diseases
- Recipients or families signed the consent form.
Who cannot join
- Organ transplant recipients whose donor is child (under the age of 18 years old)
- Patients wait-listed for multiple organ transplantation
- Unable or unwilling to follow up regularly
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Fuzhou General Hospital, Xiamen Univ Fuzhou, Fujian China
Fuzhou, Fujian, 350025
Jian ming Tan, 86-13375918000, tjming156@xmu.edu.cn
Jun Lun, 86-13599091436, junlu.heather@xmu.edu.cn
About this study
Official title: Microchimerism and cfDNA as Biomarkers for Acute Rejection After Organ Transplantation
Organ transplantation has become an effective therapy for patients with end-stage organ failure at present. Rejection is still the most common cause of early dysfunction after organ transplantation. A large number of experimental and clinical data are suggesting that the formation of microchimer can successfully achieve donor-specific immune tolerance after transplantation. The formation of microchimerism may be one of the long-term survival mechanisms of transplantation, and the detection of microchimerism after transplantation can effectively predict the rejection of grafts. Scientists from Stanford University in the United States continued to report in 2014 and 2015 that using a new generation of high-throughput sequencing technology (NGS) to detect the level of free DNA from donor in blood plasma of recipients after cardiac and lung transplantation. The investigators found the level of free DNA in donor significantly increased when acute or chronic rejection happens, thus it may be used as a reflection of rejection or graft injury markers.
It has been reported that microchimerization and donor free DNA levels are associated with rejection after organ transplantation, but these studies are mostly based on a small number of cases and the results of which re qualitative and can not provide a specific microchimerization rate due to limited detection techniques. Therefore, in order to clarify the role of microchimerism and the level of cell-free DNA in donor in organ transplantation tolerance, it is necessary to use a new generation of detection technology for multi-center study with large samples.
Read more
Clinical trial was used to evaluate the clinical prediction and diagnostic value of microchimerization rate and donor cfDNA for acute rejection after organ transplantation.
950 cases of organ transplantation, of which 600 cases of renal transplantation, 300 cases of liver transplantation and 50 cases of lung transplantation.8 ml peripheral blood was collected in 1 tubes with EDTA anticoagulation. The timing of the collection was as follows: Patients with routine treatment after transplantation were preformed once every one weeks for one months and then every 3 month until the one year. In case of acute rejection, the additional blood was collected once on the day of diagnosis, and once after the treatment remission. All the samples were detected for microchimerism and cfDNA.
Read the detailed description
Organ transplantation has become an effective therapy for patients with end-stage organ failure at present. Since the launch of pilot voluntary organ donation after death of citizens in 2010, the voluntary organ donation has become the only legitimate source of organ transplants in 2015, and the transition from relying on the judicial channels to obtain the organs to voluntary donation of citizens has been successfully achieved in China, donation cases and the number increased year by year. At present, the annual number of organ transplantation in China has exceeded 10,000 cases, of which kidney transplantation and liver transplantation were in the lead, respectively with more than 5000 cases and 2000 cases.
Rejection is still the most common cause of early dysfunction after organ transplantation, and the mismatching of major histocompatibility antigens (MHC, human MHC, also known as HLA) of the donor and recipient is the major cause of rejection after transplantation. Therefore, the importance of matching in organ transplantation has been widely accepted. HLA typing and HLA high resolution typing are becoming more and more common. At the same time, the latest international research shows that low-resolution HLA typing in organ transplantation also can cause significant rejection, while HLA high-resolution typing, the future trend, can improve the overall survival rate. Furthermore, NGS high-throughput sequencing will push HLA high-resolution classification to a new height.
Besides HLA matching, recipients can set up specific immune tolerance to donor grafts which will significantly affect long-term survival after operation. A large number of experimental and clinical data have suggested that the microchimerism formation can successfully facilitate donor-specific immune tolerance after transplantation. Chimera refers to the condition of the cells from the donor and from the recipient coexist and move to each other as that the donor cells exist in the recipient body after receiving the allograft or xenograft transplantation and the recipient cells exist in the graft as well. Among them, microchimera refers to the low levels of donor cells (usually less than 0.01%) in the peripheral blood circulation of transplant recipients, which is commonly seen in the patients with solid organ transplantation. The concept of microchimerism was first proposed by Thomas Starzl in the Medicine School of University of Pittsburgh in the 1990s, which pointed out that between the microchimerism and transplant immune tolerance lie a possible cause and effect relationship. The long-standing presence of microchimerism can lead to the recipient's tolerance to the donor organ. The more passer-by cells the organ has, the more cells it shifts out, making it easier to form transplantation tolerance, which explains the phenomenon of the mildest rejection after liver transplantation.
Several methods have been found to induce microchimerism, including donor-specific transfusion, donor bone marrow cell infusion, donor leukocyte infusion, spleen slice combined with organ transplantation and so on.
The formation of microchimerism is probably one of the long-term survival mechanisms of the transplanted graft, and the detection of microchimerism after transplantation can effectively predict the immune tolerance and rejection of the graft, while there is no very effective quantitation method.. In addition, the relationship between microchimerism and immunotolerance remains questionable, such as to what level of the clinical microchimerism formation that suggests stable immune tolerance, and whether it is possible to determine the withdrawal of immunosuppressive agents by the detection of microchimerism and etc., these are urgent problems remained to be solved and clarified. Based on the Insertion Deletion (InDel) site combined with quantitative real-time polymerase chain reaction, the detection sensitivity can reach 0.001% to 0.01%, which can accurately quantify the microchimerism level and dynamically monitor microchimerism after the transplantation.
At the same time, scientists from Stanford University in the United States continued to report in 2014 and 2015 that using a new generation of high-throughput sequencing technology (NGS) to detect the level of donor derived cell free DNA(cf DNA) in blood plasma of recipients after cardiac and lung transplantation. The investigators found that the level of donor-derived cf DNA was significantly increased when acute or chronic rejection happens, thus it could be used as a marker to reflect rejection or graft injury.
It has been reported that microchimerization and donor-cfDNA levels are correlated with rejection after organ transplantation, but these studies are mostly based on a small number of cases and the results of which are qualitative or with low resolution value due to limited detection techniques thus can not provide a specific microchimerism rate.
Therefore, The investigators need to clarify the role of microchimerism and the level of donor -derived cf DNA during graft injury as well as rejection after transplantation using a new generation of detection technology for multi-center study with large sample size.
In this study, 950 cases of organ transplantation, of which 600 cases of renal transplantation, 300 cases of liver transplantation and 50 cases of lung transplantation will be recruited and detected. 8 ml peripheral blood will be collected in 1 tubes with EDTA anticoagulation. The time points of the collection are as follows: Patients with routine treatment after transplantation are preformed once a week for 1 month and then at 3, 6 and 12 months after transplantation. In case of acute rejection, the additional blood will be collected once on the day of diagnosis, and once after 7 days treatment remission. All the samples were detected for microchimerism and cfDNA.
- Conditions
- Organ Transplant Rejection
- Being tested
- no interventions
- Keywords
- organ transplantation, cfDNA, microchimerism, acute rejection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
no interventionsOther
no interventions
| Study group | Role | What they receive |
|---|---|---|
| Acute rejection | Not described Receives: Other: no interventions | |
| No acute rejection | Not described Receives: Other: no interventions |
What is being measured
The primary outcome is the main question the study is designed to answer.
Quantification of the donor microchimerism in recipients was conducted once a week for 1 month and then at 3, 6 and 12 months after transplantation.
Around the 8mL peripheral whole blood was collected and the DNA in hemocytes was extracted for qPCR analysis. During which 30 target genomic genes were amplified, the donor microchimerism rate was quantified by former differentiating of InDel sites between the donor and the recipient.
Measured: 2017.4.1-2021.4.31
Secondary outcomes (1)
Quantification of the donor derived cfDNA rate in recipients was conducted once a week for 1 month and then at 3, 6 and 12 months after transplantation.
Around the 8mL peripheral whole blood was collected and the plasma was separated for following next-generation-sequencing by Illumina system (USA). The genotyping of the donor and the recipient
Measured: 2017.4.1-2021.4.31
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2017
- Study start1 Mar 2017
- Primary completion28 Sep 2021 (estimated)
- Study completion31 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (28)Papers the sponsor has linked to this study.
- Other trials for Organ Transplant 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
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 950 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fuzhou General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- 309th Hospital of Chinese People's Liberation Army, Tianjin First Central Hospital, RenJi Hospital, Fudan University, Ruijin Hospital, First Affiliated Hospital, Sun Yat-Sen University, Third Affiliated Hospital, Sun Yat-Sen University, Huazhong University of Science and Technology, West China Hospital, Central South University, The Third Xiangya Hospital of Central South University, First Affiliated Hospital Xi'an Jiaotong University, Qianfoshan Hospital, Wuxi People's Hospital, Second Affiliated Hospital of Guangzhou Medical University
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03255265
- Sponsor's protocol ID
- cf-DNA
- Acronym
- CSMCDTITAROT
- Status last verified
- Apr 2017
- First submitted
- 13 Feb 2017
- Last updated
- 21 Aug 2017
- Results posted
- No
Publications
Adams KM, Nelson JL. Microchimerism: an investigative frontier in autoimmunity and transplantation. JAMA. 2004 Mar 3;291(9):1127-31. doi: 10.1001/jama.291.9.1127.
PubMed 14996783Akamatsu Y, Ohkohchi N, Seya K, Satomi S. Analysis of bilirubin fraction in the bile for early diagnosis of acute rejection in living related liver transplantation. Tohoku J Exp Med. 1997 Jan;181(1):145-54. doi: 10.1620/tjem.181.145.
PubMed 9149349Aljurf M, Abalkhail H, Alseraihy A, Mohamed SY, Ayas M, Alsharif F, Alzahrani H, Al-Jefri A, Aldawsari G, Al-Ahmari A, Belgaumi AF, Walter CU, El-Solh H, Rasheed W, Albitar M. Chimerism Analysis of Cell-Free DNA in Patients Treated with Hematopoietic Stem Cell Transplantation May Predict Early Relapse in Patients with Hematologic Malignancies. Biotechnol Res Int. 2016;2016:8589270. doi: 10.1155/2016/8589270. Epub 2016 Feb 23.
PubMed 27006832Ascher NL. Microchimerism in organ transplantation. Liver Transpl Surg. 1995 Jan;1(1):43-6. doi: 10.1002/lt.500010109. No abstract available.
PubMed 9346540Avolio AW, Gozzo ML, Forni L, Agnes S, Colacicco L, Barbaresi G, Magalini SC, Castagneto M. Mitochondrial/cytoplasmic enzyme ratio for the diagnosis of acute rejection after liver transplantation: sensitivity and specificity. Transplant Proc. 1992 Dec;24(6):2572-3. No abstract available.
PubMed 1361263Bakr MA, Nagib AM, Donia AF. Induction immunosuppressive therapy in kidney transplantation. Exp Clin Transplant. 2014 Mar;12 Suppl 1:60-9. doi: 10.6002/ect.25liver.l58.
PubMed 24635795Bamgbola O. Metabolic consequences of modern immunosuppressive agents in solid organ transplantation. Ther Adv Endocrinol Metab. 2016 Jun;7(3):110-27. doi: 10.1177/2042018816641580. Epub 2016 Mar 30.
PubMed 27293540Beck J, Oellerich M, Schulz U, Schauerte V, Reinhard L, Fuchs U, Knabbe C, Zittermann A, Olbricht C, Gummert JF, Shipkova M, Birschmann I, Wieland E, Schutz E. Donor-Derived Cell-Free DNA Is a Novel Universal Biomarker for Allograft Rejection in Solid Organ Transplantation. Transplant Proc. 2015 Oct;47(8):2400-3. doi: 10.1016/j.transproceed.2015.08.035.
PubMed 26518940Biancofiore G, Pucci L, Cerutti E, Penno G, Pardini E, Esposito M, Bindi L, Pelati E, Romanelli A, Triscornia S, Salvadorini MP, Stratta C, Lanfranco G, Pellegrini G, Del Prato S, Salizzoni M, Mosca F, Filipponi F. Cystatin C as a marker of renal function immediately after liver transplantation. Liver Transpl. 2006 Feb;12(2):285-91. doi: 10.1002/lt.20657.
PubMed 16447198Capron A, Haufroid V, Wallemacq P. Intra-cellular immunosuppressive drugs monitoring: A step forward towards better therapeutic efficacy after organ transplantation? Pharmacol Res. 2016 Sep;111:610-618. doi: 10.1016/j.phrs.2016.07.027. Epub 2016 Jul 25.
PubMed 27468645Chen Y, Tai Q, Hong S, Kong Y, Shang Y, Liang W, Guo Z, He X. Pretransplantation soluble CD30 level as a predictor of acute rejection in kidney transplantation: a meta-analysis. Transplantation. 2012 Nov 15;94(9):911-8. doi: 10.1097/TP.0b013e31826784ad.
PubMed 23052636De Vlaminck I, Martin L, Kertesz M, Patel K, Kowarsky M, Strehl C, Cohen G, Luikart H, Neff NF, Okamoto J, Nicolls MR, Cornfield D, Weill D, Valantine H, Khush KK, Quake SR. Noninvasive monitoring of infection and rejection after lung transplantation. Proc Natl Acad Sci U S A. 2015 Oct 27;112(43):13336-41. doi: 10.1073/pnas.1517494112. Epub 2015 Oct 12.
PubMed 26460048De Vlaminck I, Valantine HA, Snyder TM, Strehl C, Cohen G, Luikart H, Neff NF, Okamoto J, Bernstein D, Weisshaar D, Quake SR, Khush KK. Circulating cell-free DNA enables noninvasive diagnosis of heart transplant rejection. Sci Transl Med. 2014 Jun 18;6(241):241ra77. doi: 10.1126/scitranslmed.3007803.
PubMed 24944192Delville M, Charreau B, Rabant M, Legendre C, Anglicheau D. Pathogenesis of non-HLA antibodies in solid organ transplantation: Where do we stand? Hum Immunol. 2016 Nov;77(11):1055-1062. doi: 10.1016/j.humimm.2016.05.021. Epub 2016 May 26.
PubMed 27237040Deschaseaux F, Delgado D, Pistoia V, Giuliani M, Morandi F, Durrbach A. HLA-G in organ transplantation: towards clinical applications. Cell Mol Life Sci. 2011 Feb;68(3):397-404. doi: 10.1007/s00018-010-0581-6. Epub 2010 Nov 20.
PubMed 21103908
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Microchimerism and cfDNA as Biomarkers for Acute Rejection After Organ Transplantation
- ClinicalTrials.gov ID
- NCT03255265
- Acronym / sponsor ID
- CSMCDTITAROT / cf-DNA
- Conditions
- Organ Transplant Rejection
- Keywords
- organ transplantation, cfDNA, microchimerism, acute rejection
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 950 participants (estimated)
- Lead sponsor
- Fuzhou General HospitalUniversity, hospital or other
- Collaborators
- 309th Hospital of Chinese People's Liberation Army, Tianjin First Central Hospital, RenJi Hospital, Fudan University, Ruijin Hospital, First Affiliated Hospital, Sun Yat-Sen University, Third Affiliated Hospital, Sun Yat-Sen University, Huazhong University of Science and Technology, West China Hospital, Central South University, The Third Xiangya Hospital of Central South University, First Affiliated Hospital Xi'an Jiaotong University, Qianfoshan Hospital, Wuxi People's Hospital, Second Affiliated Hospital of Guangzhou Medical University
- Study start
- 1 Mar 2017 (actual)
- Primary completion
- 28 Sep 2021 (estimated)
- Study completion
- 31 Dec 2021 (estimated)
- First posted
- 21 Aug 2017 (actual)
- 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.
Organ transplantation has become an effective therapy for patients with end-stage organ failure at present. Rejection is still the most common cause of early dysfunction after organ transplantation. A large number of experimental and clinical data are suggesting that the formation of microchimer can successfully achieve donor-specific immune tolerance after transplantation. The formation of microchimerism may be one of the long-term survival mechanisms of transplantation, and the detection of microchimerism after transplantation can effectively predict the rejection of grafts. Scientists from Stanford University in the United States continued to report in 2014 and 2015 that using a new generation of high-throughput sequencing technology (NGS) to detect the level of free DNA from donor in blood plasma of recipients after cardiac and lung transplantation. The investigators found the level of free DNA in donor significantly increased when acute or chronic rejection happens, thus it may be used as a reflection of rejection or graft injury markers.
It has been reported that microchimerization and donor free DNA levels are associated with rejection after organ transplantation, but these studies are mostly based on a small number of cases and the results of which re qualitative and can not provide a specific microchimerization rate due to limited detection techniques. Therefore, in order to clarify the role of microchimerism and the level of cell-free DNA in donor in organ transplantation tolerance, it is necessary to use a new generation of detection technology for multi-center study with large samples.
Clinical trial was used to evaluate the clinical prediction and diagnostic value of microchimerization rate and donor cfDNA for acute rejection after organ transplantation.
950 cases of organ transplantation, of which 600 cases of renal transplantation, 300 cases of liver transplantation and 50 cases of lung transplantation.8 ml peripheral blood was collected in 1 tubes with EDTA anticoagulation. The timing of the collection was as follows: Patients with routine treatment after transplantation were preformed once every one weeks for one months and then every 3 month until the one year. In case of acute rejection, the additional blood was collected once on the day of diagnosis, and once after the treatment remission. All the samples were detected for microchimerism and cfDNA.
Detailed description
Organ transplantation has become an effective therapy for patients with end-stage organ failure at present. Since the launch of pilot voluntary organ donation after death of citizens in 2010, the voluntary organ donation has become the only legitimate source of organ transplants in 2015, and the transition from relying on the judicial channels to obtain the organs to voluntary donation of citizens has been successfully achieved in China, donation cases and the number increased year by year. At present, the annual number of organ transplantation in China has exceeded 10,000 cases, of which kidney transplantation and liver transplantation were in the lead, respectively with more than 5000 cases and 2000 cases.
Rejection is still the most common cause of early dysfunction after organ transplantation, and the mismatching of major histocompatibility antigens (MHC, human MHC, also known as HLA) of the donor and recipient is the major cause of rejection after transplantation. Therefore, the importance of matching in organ transplantation has been widely accepted. HLA typing and HLA high resolution typing are becoming more and more common. At the same time, the latest international research shows that low-resolution HLA typing in organ transplantation also can cause significant rejection, while HLA high-resolution typing, the future trend, can improve the overall survival rate. Furthermore, NGS high-throughput sequencing will push HLA high-resolution classification to a new height.
Besides HLA matching, recipients can set up specific immune tolerance to donor grafts which will significantly affect long-term survival after operation. A large number of experimental and clinical data have suggested that the microchimerism formation can successfully facilitate donor-specific immune tolerance after transplantation. Chimera refers to the condition of the cells from the donor and from the recipient coexist and move to each other as that the donor cells exist in the recipient body after receiving the allograft or xenograft transplantation and the recipient cells exist in the graft as well. Among them, microchimera refers to the low levels of donor cells (usually less than 0.01%) in the peripheral blood circulation of transplant recipients, which is commonly seen in the patients with solid organ transplantation. The concept of microchimerism was first proposed by Thomas Starzl in the Medicine School of University of Pittsburgh in the 1990s, which pointed out that between the microchimerism and transplant immune tolerance lie a possible cause and effect relationship. The long-standing presence of microchimerism can lead to the recipient's tolerance to the donor organ. The more passer-by cells the organ has, the more cells it shifts out, making it easier to form transplantation tolerance, which explains the phenomenon of the mildest rejection after liver transplantation.
Several methods have been found to induce microchimerism, including donor-specific transfusion, donor bone marrow cell infusion, donor leukocyte infusion, spleen slice combined with organ transplantation and so on.
The formation of microchimerism is probably one of the long-term survival mechanisms of the transplanted graft, and the detection of microchimerism after transplantation can effectively predict the immune tolerance and rejection of the graft, while there is no very effective quantitation method.. In addition, the relationship between microchimerism and immunotolerance remains questionable, such as to what level of the clinical microchimerism formation that suggests stable immune tolerance, and whether it is possible to determine the withdrawal of immunosuppressive agents by the detection of microchimerism and etc., these are urgent problems remained to be solved and clarified. Based on the Insertion Deletion (InDel) site combined with quantitative real-time polymerase chain reaction, the detection sensitivity can reach 0.001% to 0.01%, which can accurately quantify the microchimerism level and dynamically monitor microchimerism after the transplantation.
At the same time, scientists from Stanford University in the United States continued to report in 2014 and 2015 that using a new generation of high-throughput sequencing technology (NGS) to detect the level of donor derived cell free DNA(cf DNA) in blood plasma of recipients after cardiac and lung transplantation. The investigators found that the level of donor-derived cf DNA was significantly increased when acute or chronic rejection happens, thus it could be used as a marker to reflect rejection or graft injury.
It has been reported that microchimerization and donor-cfDNA levels are correlated with rejection after organ transplantation, but these studies are mostly based on a small number of cases and the results of which are qualitative or with low resolution value due to limited detection techniques thus can not provide a specific microchimerism rate.
Therefore, The investigators need to clarify the role of microchimerism and the level of donor -derived cf DNA during graft injury as well as rejection after transplantation using a new generation of detection technology for multi-center study with large sample size.
In this study, 950 cases of organ transplantation, of which 600 cases of renal transplantation, 300 cases of liver transplantation and 50 cases of lung transplantation will be recruited and detected. 8 ml peripheral blood will be collected in 1 tubes with EDTA anticoagulation. The time points of the collection are as follows: Patients with routine treatment after transplantation are preformed once a week for 1 month and then at 3, 6 and 12 months after transplantation. In case of acute rejection, the additional blood will be collected once on the day of diagnosis, and once after 7 days treatment remission. All the samples were detected for microchimerism and cfDNA.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Acute rejection | – | Other: no interventions |
| No acute rejection | – | Other: no interventions |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- aged above 18 years old single organ transplant patients (first or again); Guardian or self-signed informed consent.
Key inclusion criteria (4 listed)
- Single-organ transplant recipients aged above 18 years old Recipients of re-do organ transplants
- Recipients with no systemic acute or chronic infections, infectious diseases;
- Recipients with no severe systemic diseases and/or spiritual system diseases
- Recipients or families signed the consent form.
Key exclusion criteria (3 listed)
- Organ transplant recipients whose donor is child (under the age of 18 years old)
- Patients wait-listed for multiple organ transplantation
- Unable or unwilling to follow up regularly
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| no interventionsno interventions | Other | Acute rejection, No acute rejection |
Primary outcome
Quantification of the donor microchimerism in recipients was conducted once a week for 1 month and then at 3, 6 and 12 months after transplantation.
Time frame: 2017.4.1-2021.4.31
Around the 8mL peripheral whole blood was collected and the DNA in hemocytes was extracted for qPCR analysis. During which 30 target genomic genes were amplified, the donor microchimerism rate was quantified by former differentiating of InDel sites between the donor and the recipient.
1 secondary outcome
Quantification of the donor derived cfDNA rate in recipients was conducted once a week for 1 month and then at 3, 6 and 12 months after transplantation.
Time frame: 2017.4.1-2021.4.31
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2017.
- Background: PubMed 14996783Adams KM, Nelson JL. Microchimerism: an investigative frontier in autoimmunity and transplantation. JAMA. 2004 Mar 3;291(9):1127-31. doi: 10.1001/jama.291.9.1127.
- Background: PubMed 9149349Akamatsu Y, Ohkohchi N, Seya K, Satomi S. Analysis of bilirubin fraction in the bile for early diagnosis of acute rejection in living related liver transplantation. Tohoku J Exp Med. 1997 Jan;181(1):145-54. doi: 10.1620/tjem.181.145.
- Background: PubMed 27006832Aljurf M, Abalkhail H, Alseraihy A, Mohamed SY, Ayas M, Alsharif F, Alzahrani H, Al-Jefri A, Aldawsari G, Al-Ahmari A, Belgaumi AF, Walter CU, El-Solh H, Rasheed W, Albitar M. Chimerism Analysis of Cell-Free DNA in Patients Treated with Hematopoietic Stem Cell Transplantation May Predict Early Relapse in Patients with Hematologic Malignancies. Biotechnol Res Int. 2016;2016:8589270. doi: 10.1155/2016/8589270. Epub 2016 Feb 23.
- Background: PubMed 9346540Ascher NL. Microchimerism in organ transplantation. Liver Transpl Surg. 1995 Jan;1(1):43-6. doi: 10.1002/lt.500010109. No abstract available.
- Background: PubMed 1361263Avolio AW, Gozzo ML, Forni L, Agnes S, Colacicco L, Barbaresi G, Magalini SC, Castagneto M. Mitochondrial/cytoplasmic enzyme ratio for the diagnosis of acute rejection after liver transplantation: sensitivity and specificity. Transplant Proc. 1992 Dec;24(6):2572-3. No abstract available.
- Background: PubMed 24635795Bakr MA, Nagib AM, Donia AF. Induction immunosuppressive therapy in kidney transplantation. Exp Clin Transplant. 2014 Mar;12 Suppl 1:60-9. doi: 10.6002/ect.25liver.l58.
- Background: PubMed 27293540Bamgbola O. Metabolic consequences of modern immunosuppressive agents in solid organ transplantation. Ther Adv Endocrinol Metab. 2016 Jun;7(3):110-27. doi: 10.1177/2042018816641580. Epub 2016 Mar 30.
- Background: PubMed 26518940Beck J, Oellerich M, Schulz U, Schauerte V, Reinhard L, Fuchs U, Knabbe C, Zittermann A, Olbricht C, Gummert JF, Shipkova M, Birschmann I, Wieland E, Schutz E. Donor-Derived Cell-Free DNA Is a Novel Universal Biomarker for Allograft Rejection in Solid Organ Transplantation. Transplant Proc. 2015 Oct;47(8):2400-3. doi: 10.1016/j.transproceed.2015.08.035.
- Background: PubMed 16447198Biancofiore G, Pucci L, Cerutti E, Penno G, Pardini E, Esposito M, Bindi L, Pelati E, Romanelli A, Triscornia S, Salvadorini MP, Stratta C, Lanfranco G, Pellegrini G, Del Prato S, Salizzoni M, Mosca F, Filipponi F. Cystatin C as a marker of renal function immediately after liver transplantation. Liver Transpl. 2006 Feb;12(2):285-91. doi: 10.1002/lt.20657.
- Background: PubMed 27468645Capron A, Haufroid V, Wallemacq P. Intra-cellular immunosuppressive drugs monitoring: A step forward towards better therapeutic efficacy after organ transplantation? Pharmacol Res. 2016 Sep;111:610-618. doi: 10.1016/j.phrs.2016.07.027. Epub 2016 Jul 25.
- Background: PubMed 23052636Chen Y, Tai Q, Hong S, Kong Y, Shang Y, Liang W, Guo Z, He X. Pretransplantation soluble CD30 level as a predictor of acute rejection in kidney transplantation: a meta-analysis. Transplantation. 2012 Nov 15;94(9):911-8. doi: 10.1097/TP.0b013e31826784ad.
- Background: PubMed 26460048De Vlaminck I, Martin L, Kertesz M, Patel K, Kowarsky M, Strehl C, Cohen G, Luikart H, Neff NF, Okamoto J, Nicolls MR, Cornfield D, Weill D, Valantine H, Khush KK, Quake SR. Noninvasive monitoring of infection and rejection after lung transplantation. Proc Natl Acad Sci U S A. 2015 Oct 27;112(43):13336-41. doi: 10.1073/pnas.1517494112. Epub 2015 Oct 12.
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Extended Validation of Donor-derived Cell-free DNA in Kidney Transplant Recipients
Rejection Acute Renal, Rejection Chronic Renal
Active, not recruitingObservational study
Immune Function as Predictor of Infectious Complications and Clinical Outcome in Patients Undergoing Solid Organ Transplantation
Transplant
RecruitingObservational study
Biomarkers in Transplant Recipients to Improve Outcomes
Solid Organ Transplantation, Bone Marrow Transplantation
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Organ Transplant Rejection, run by Fuzhou General Hospital at 1 site in China.
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 4 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 21 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jian ming Tan, Chief Physician (86-13375918000, tanjm156@xmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Quantification of the donor microchimerism in recipients was conducted once a week for 1 month and then at 3, 6 and 12 months after transplantation. (time frame: 2017.4.1-2021.4.31). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03255265, which also lists 28 linked publications.
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 21 Aug 2017.