Cell-Free Nucleic AcidsNCT05226936
Study for Detection of Donor-derived Cell-free DNA After Renal Transplantation Using Devysers NGS-based Chimerism Assay.
An observational study of Cell-Free Nucleic Acids, run by Sheba Medical Center.
Trial summary
The aim of this study is to evaluate highly sensitive quantitative tests for early molecular detection of graft rejection and associated immune response from liquid biopsies in the blood from patients undergoing renal transplantation and secondly, to evaluate the evolution of de-novo HLA antibodies following renal… Read more about this study
- Who is it for?
- Ages 20 to 70 years
- Conditions the study is for
- Cell-Free Nucleic Acids
- What is being tested?
- Cell free DNA analysis
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- 1 Apr 2022to 31 Mar 2024
- How long will I take part?
- 2 Years
- 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 20 to 70 years
- All sexes
- Adult, Older adult
Study population: Patients undergoing live donor or deceased donor transplantation
Who may be able to join
- Patients older than 20 undergoing kidney transplantation -
Who cannot join
- Patients included in other studies Patients a combined transplant with other donor Patients not eligible to sign an inform consent Patients with primary non-function or those that lost their graft during the first 3 months
- -
Trial locations and contacts
No sites are listed yet.
About this study
The aim of this study is to evaluate highly sensitive quantitative tests for early molecular detection of graft rejection and associated immune response from liquid biopsies in the blood from patients undergoing renal transplantation and secondly, to evaluate the evolution of de-novo HLA antibodies following renal transplantation. Furthermore, we are interested in the correlation of tissue damage caused by rejection, as measured by the presence of dd-cfDNA, and the presence of de-novo HLA antibodies.
Read the detailed description
Each year 40-60 patients undergo renal transplant with a living donor (LD) at Karolinska University Hospital. Prior to transplantation, these patients and their donors are investigated for their immunological compatibility. This includes cytotoxic- and flow cytometric crossmatches, HLA typing as well as determination of possible presence of panel-reactive HLA antibodies (PRA). Normally these investigations are performed 2-3 months prior to renal transplantation. Once a patient has been accepted for transplantation with a given living donor, they will, prior to transplantation be asked whether they are interested in taking part of the present study. If the patient and the donor do accept, we will collect 15 mL of blood prior to transplantation using suitable sample collection tubes (Cell-Free BCT tubes). This sample will be used for screening patient and donor for specific genetic markers. Furthermore, the pretransplant samples will be used for determining the presence or absence of HLA antibodies for each patient. We aim to include up to 50 patients in the current study.
During the first 24-48 hrs after transplantation, two more samples (10 mL) from the patient will be collected to measure the potential presence of dd-cfDNA including cell-free particles such as exosomes. The cell-free DNA and RNA from all samples will be extracted, stored frozen and later sequenced. Following transplantation and initiation of the immunosuppressive therapy, samples for analysis will be obtained once every week for up to 3 months. All collected samples will be either analysed immediately or frozen for future analysis. Stored frozen samples could, at a later time point, be thawed, batched and analysed using molecular techniques including sequencing for measuring dd-cfDNA or analysis of the presence of HLA-antibodies using commercial bead-technologies (Luminex or Immucor). Results from these assays will be added to a dedicated database. The obtained laboratory results will be compared to clinical outcome including graft survival, patient survival, clinical and subclinical rejections etc. as well as other laboratory data (e.g. results from pathological examination of the graft, clinical chemistry, concentration of immunosuppressive drugs etc).
- Conditions
- Cell-Free Nucleic Acids
- Being tested
- Cell free DNA analysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cell free DNA analysisDiagnostic test
Also called Donor Specific Antibody analysis
samples will be analysed using molecular techniques including sequencing for measuring dd-cfDNA or analysis of the presence of HLA-antibodies using commercial bead-technologies (Luminex or Immucor)
What is being measured
The primary outcome is the main question the study is designed to answer.
Degree of chimerism
The fraction of cell free donor DNA will be measured after transplant
Measured: According to the study protocol before and after transplantation in defined intervals up to 3 moths
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2022
- Study start1 Apr 2022 (estimated)
- Primary completion31 Mar 2024 (estimated)
- Study completion31 Mar 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cell-Free Nucleic AcidsStudies of the same condition, open and under way.
- More trials run by Sheba Medical CenterThe sponsor's other registered studies.
- 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
- 50 participants (estimated)
- Target duration
- 2 Years
Sponsor and investigators
- Lead sponsor
- Sheba Medical Center
- Sponsor type
- Other government
- Collaborators
- Dan Hauzenberger M.D., Ph.D. Assoc. Professor, Karolinska University Hospital Sweden
- Responsible party
- Principal investigator, Prof. Eytan Mor, Sheba Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05226936
- Sponsor's protocol ID
- 9024-21-SMC
- Status last verified
- Jan 2022
- First submitted
- 27 Jan 2022
- Last updated
- 7 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The study is in collaboration with the transplant center in Sweden. Each study patients will be given a code and the coded information will be shared with our partners
Publications
Bloom RD, Bromberg JS, Poggio ED, Bunnapradist S, Langone AJ, Sood P, Matas AJ, Mehta S, Mannon RB, Sharfuddin A, Fischbach B, Narayanan M, Jordan SC, Cohen D, Weir MR, Hiller D, Prasad P, Woodward RN, Grskovic M, Sninsky JJ, Yee JP, Brennan DC; Circulating Donor-Derived Cell-Free DNA in Blood for Diagnosing Active Rejection in Kidney Transplant Recipients (DART) Study Investigators. Cell-Free DNA and Active Rejection in Kidney Allografts. J Am Soc Nephrol. 2017 Jul;28(7):2221-2232. doi: 10.1681/ASN.2016091034. Epub 2017 Mar 9.
PubMed 28280140Everly MJ, Terasaki PI. Monitoring and treating posttransplant human leukocyte antigen antibodies. Hum Immunol. 2009 Aug;70(8):655-9. doi: 10.1016/j.humimm.2009.04.019. Epub 2009 Apr 15.
PubMed 19375466Lee PC, Zhu L, Terasaki PI, Everly MJ. HLA-specific antibodies developed in the first year posttransplant are predictive of chronic rejection and renal graft loss. Transplantation. 2009 Aug 27;88(4):568-74. doi: 10.1097/TP.0b013e3181b11b72.
PubMed 19696641
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study for Detection of Donor-derived Cell-free DNA After Renal Transplantation Using Devysers NGS-based Chimerism Assay.
- ClinicalTrials.gov ID
- NCT05226936
- Acronym / sponsor ID
- 9024-21-SMC
- Conditions
- Cell-Free Nucleic Acids
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Sheba Medical CenterOther government
- Collaborators
- Dan Hauzenberger M.D., Ph.D. Assoc. Professor, Karolinska University Hospital Sweden
- Study start
- 1 Apr 2022 (estimated)
- Primary completion
- 31 Mar 2024 (estimated)
- Study completion
- 31 Mar 2024 (estimated)
- First posted
- 7 Feb 2022 (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.
The aim of this study is to evaluate highly sensitive quantitative tests for early molecular detection of graft rejection and associated immune response from liquid biopsies in the blood from patients undergoing renal transplantation and secondly, to evaluate the evolution of de-novo HLA antibodies following renal transplantation. Furthermore, we are interested in the correlation of tissue damage caused by rejection, as measured by the presence of dd-cfDNA, and the presence of de-novo HLA antibodies.
Detailed description
Each year 40-60 patients undergo renal transplant with a living donor (LD) at Karolinska University Hospital. Prior to transplantation, these patients and their donors are investigated for their immunological compatibility. This includes cytotoxic- and flow cytometric crossmatches, HLA typing as well as determination of possible presence of panel-reactive HLA antibodies (PRA). Normally these investigations are performed 2-3 months prior to renal transplantation. Once a patient has been accepted for transplantation with a given living donor, they will, prior to transplantation be asked whether they are interested in taking part of the present study. If the patient and the donor do accept, we will collect 15 mL of blood prior to transplantation using suitable sample collection tubes (Cell-Free BCT tubes). This sample will be used for screening patient and donor for specific genetic markers. Furthermore, the pretransplant samples will be used for determining the presence or absence of HLA antibodies for each patient. We aim to include up to 50 patients in the current study.
During the first 24-48 hrs after transplantation, two more samples (10 mL) from the patient will be collected to measure the potential presence of dd-cfDNA including cell-free particles such as exosomes. The cell-free DNA and RNA from all samples will be extracted, stored frozen and later sequenced. Following transplantation and initiation of the immunosuppressive therapy, samples for analysis will be obtained once every week for up to 3 months. All collected samples will be either analysed immediately or frozen for future analysis. Stored frozen samples could, at a later time point, be thawed, batched and analysed using molecular techniques including sequencing for measuring dd-cfDNA or analysis of the presence of HLA-antibodies using commercial bead-technologies (Luminex or Immucor). Results from these assays will be added to a dedicated database. The obtained laboratory results will be compared to clinical outcome including graft survival, patient survival, clinical and subclinical rejections etc. as well as other laboratory data (e.g. results from pathological examination of the graft, clinical chemistry, concentration of immunosuppressive drugs etc).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 2 Years
Who may qualify
- Ages
- 20 to 70 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Patients undergoing live donor or deceased donor transplantation
Key inclusion criteria (1 listed)
- Patients older than 20 undergoing kidney transplantation -
Key exclusion criteria (2 listed)
- Patients included in other studies Patients a combined transplant with other donor Patients not eligible to sign an inform consent Patients with primary non-function or those that lost their graft during the first 3 months
- -
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 |
|---|---|---|
| Cell free DNA analysisAlso: Donor Specific Antibody analysissamples will be analysed using molecular techniques including sequencing for measuring dd-cfDNA or analysis of the presence of HLA-antibodies using commercial bead-technologies (Luminex or Immucor) | Diagnostic test | – |
Primary outcome
Degree of chimerism
Time frame: According to the study protocol before and after transplantation in defined intervals up to 3 moths
The fraction of cell free donor DNA will be measured after transplant
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2022.
- Background: PubMed 28280140Bloom RD, Bromberg JS, Poggio ED, Bunnapradist S, Langone AJ, Sood P, Matas AJ, Mehta S, Mannon RB, Sharfuddin A, Fischbach B, Narayanan M, Jordan SC, Cohen D, Weir MR, Hiller D, Prasad P, Woodward RN, Grskovic M, Sninsky JJ, Yee JP, Brennan DC; Circulating Donor-Derived Cell-Free DNA in Blood for Diagnosing Active Rejection in Kidney Transplant Recipients (DART) Study Investigators. Cell-Free DNA and Active Rejection in Kidney Allografts. J Am Soc Nephrol. 2017 Jul;28(7):2221-2232. doi: 10.1681/ASN.2016091034. Epub 2017 Mar 9.
- Background: PubMed 19375466Everly MJ, Terasaki PI. Monitoring and treating posttransplant human leukocyte antigen antibodies. Hum Immunol. 2009 Aug;70(8):655-9. doi: 10.1016/j.humimm.2009.04.019. Epub 2009 Apr 15.
- Background: PubMed 19696641Lee PC, Zhu L, Terasaki PI, Everly MJ. HLA-specific antibodies developed in the first year posttransplant are predictive of chronic rejection and renal graft loss. Transplantation. 2009 Aug 27;88(4):568-74. doi: 10.1097/TP.0b013e3181b11b72.
- Individual participant dataSharing planned: Yes. The study is in collaboration with the transplant center in Sweden. Each study patients will be given a code and the coded information will be shared with our partners
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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.
Questions about this trial
What is this clinical trial studying?
An observational study of Cell-Free Nucleic Acids, run by Sheba Medical Center.
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 2 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 7 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
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 Eytan Mor, MD (052-2297779, eytan.mor@sheba.health.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Degree of chimerism (time frame: According to the study protocol before and after transplantation in defined intervals up to 3 moths). 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 NCT05226936, which also lists 3 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 7 Feb 2022.