<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03759535</url>
  </required_header>
  <id_info>
    <org_study_id>RenJiH-renal transplantation01</org_study_id>
    <nct_id>NCT03759535</nct_id>
  </id_info>
  <brief_title>Study in Detection cfDNA for the Early-stage Diagnosis of Acute Rejection Post-renal Transplantation</brief_title>
  <official_title>Research on the Detection of Donor Derived Cell Free DNA （cfDNA）for the Early-stage Diagnosis of Acute Rejection Reaction Post Kidney Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>RenJi Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>RenJi Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Acute rejection (AR) is still one of the major complications after kidney transplantation.&#xD;
      The current diagnosis measure for AR is primarily pathological puncture test and hematuria&#xD;
      biomarker detection, yet due to their inferior performance on timeliness, the allograft&#xD;
      kidneys usually have been in severe conditions when the diagnoses take place. Donor derived&#xD;
      cell free DNA (dd-cfDNA) is utilized as a measure for &quot;liquid biopsy&quot;, it can predict acute&#xD;
      rejection at very early periods, and it is easy to operate, with fewer invasive injuries, and&#xD;
      can reflect related conditions in a timely manner, etc.. This study plans to utilize&#xD;
      second-generation sequencing technology to systematically evaluate the abundance variations&#xD;
      of nuclear genome and mitocondria derived dd-cfDNA in the kidney transplant recipients' blood&#xD;
      and urine, thus it can assist in accumulating more proof for the clinical utilization of&#xD;
      dd-cfDNA from different sources at the early stages of AR in evidence-based medicine, and lay&#xD;
      foundation for the development of dd-cfDNA based early-stage rejection detection tools&#xD;
      afterkidney transplantation surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      With the growing development of kidney transplant technologies and immunosuppressive&#xD;
      therapies, the number of end-stage renal disease patients receiving kidney transplant has&#xD;
      been increasing. Acute rejection (AR) is one of the main complications for kidney&#xD;
      transplantation, and AR is the major reason for lowering graft survival rate and for graft&#xD;
      malfunction, thus the timely detection of AR and early interventions are crucial. The current&#xD;
      clinical measures for the detection of AR include pathological puncture test and hematuria&#xD;
      biomarker detection. Yet pathological tests are invasive, limited to sampling errors and the&#xD;
      existing perception differences among observants, and with other disadvantages such as&#xD;
      expensiveness, poor patient compliance, and related complications. Hematuria biomarker&#xD;
      detection is slow in response and low in the sensitivity and specificity for reflecting the&#xD;
      organs' metabolic index in the diagnosis of acute rejection injury. Though the monitoring of&#xD;
      immunosuppressant drugs, immune molecules and cytokines in the blood circulation can both&#xD;
      provide certain value for the evaluation of patients' immune status after organ transplant,&#xD;
      these factors are not good indicators for the early-stage diagnosis of allograft injury.&#xD;
      Donor derived cell free DNA (dd-cfDNA) is utilized as a measure for &quot;liquid biopsy&quot;, it is&#xD;
      easy to operate, with less invasiveness, and it can reflect related conditions in a timely&#xD;
      manner, etc.. This measure can detect the injury degree for allograft, and the index will&#xD;
      rise before fluctuation reflection of the syndrome and related laboratory indexes, which is&#xD;
      crucial for the very early-stage diagnosis of allograft acute rejection, and the further&#xD;
      prevention of allograft injury. In the mean time, dd-cfDNA assumes high utilization value for&#xD;
      the monitoring of immunosuppressive conditions, and therefore providing instructions for the&#xD;
      optimization of the immunosuppressive treatment.&#xD;
&#xD;
      Under the condition of signed informed consent, the study protocols were scheduled as below:&#xD;
&#xD;
      Self-control study protocol:&#xD;
&#xD;
      20 to-receive-kidney-transplant patients are randomized, the self-control study protocol is&#xD;
      utilized for each patient as the following.&#xD;
&#xD;
      Before the kidney transplant surgery, 1ml of peripheral EDTA anticoagulant from the&#xD;
      recipients, and 1ml of peripheral EDTA anticoagulant from the donors are collected.&#xD;
&#xD;
      In 1 week, 2 weeks, 3 weeks' time after the kidney transplant surgeries, 8 to 10 ml of&#xD;
      peripheral blood from the recipients using cfDNA blood collection tubes, and 10 to 15 ml of&#xD;
      midstream urine are collected respectively.&#xD;
&#xD;
      Inclusion criteria:&#xD;
&#xD;
      *Patients are suitable for kidney transplant surgeries.&#xD;
&#xD;
      Exclusion criteria:&#xD;
&#xD;
        -  Patients have failed in the transplant surgeries.&#xD;
&#xD;
        -  Patients have no urine 1 week after the transplant surgeries.&#xD;
&#xD;
        -  Patients have severe infectious complications after the transplant surgeries. b, Case&#xD;
           group: For 20 patients that have been diagnosed with acute rejection on the first&#xD;
           visits, 8 to 10 ml of EDTA anticoagulant, 10 to 15 ml of midstream urine, 5 ml of saliva&#xD;
           are collected before the treatment, 1 week and 2 weeks after the adjustment of the&#xD;
           anti-rejection treatment, 8 to 10 ml of blood using cfDNA blood collection tubes, 10 to&#xD;
           15 ml of midstream urine, 5 ml of saliva are collected respectively.&#xD;
&#xD;
      Inclusion criteria:&#xD;
&#xD;
      Control group:&#xD;
&#xD;
        -  The allograft kidneys function normally.&#xD;
&#xD;
        -  The rejection of allograft kidneys are excluded.&#xD;
&#xD;
        -  The patients have no infectious complications.&#xD;
&#xD;
      Case group:&#xD;
&#xD;
        -  There is obvious evidence for acute rejection of the allograft kidneys.&#xD;
&#xD;
        -  The patients have no infectious complications.&#xD;
&#xD;
      Exclusion criteria:&#xD;
&#xD;
        -  The patients have infectious complications.&#xD;
&#xD;
        -  The patients have tumors.&#xD;
&#xD;
        -  The patients are pregnant.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">December 1, 2018</start_date>
  <completion_date type="Anticipated">September 30, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Renal allograft injury Renal allograft injury</measure>
    <time_frame>2 months</time_frame>
    <description>serum creatinine level</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Kidney Transplant Failure and Rejection</condition>
  <arm_group>
    <arm_group_label>Control group and Case group</arm_group_label>
    <description>Control group:&#xD;
The allograft kidneys function normally. The rejection of allograft kidneys are excluded. The patients have no infectious complications.&#xD;
Case group:&#xD;
There is obvious evidence for acute rejection of the allograft kidneys. The patients have no infectious complications.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Acute rejection</intervention_name>
    <description>Donor derived cell free DNA</description>
    <arm_group_label>Control group and Case group</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Donor derived cell free DNA (dd-cfDNA) is utilized as a measure for &quot;liquid biopsy&quot;, it is&#xD;
      easy to operate, with less invasiveness, and it can reflect related conditions in a timely&#xD;
      manner，etc.. This measure can detect the injury degree for allograft, and the index will rise&#xD;
      before fluctuation reflection of the syndrome and related laboratory indexes, which is&#xD;
      crucial for the very early-stage diagnosis of allograft acute rejection, and the further&#xD;
      prevention of allograft injury. In the mean time, dd-cfDNA assumes high utilization value for&#xD;
      the monitoring of immunosuppressive conditions, and therefore providing instructions for the&#xD;
      optimization of the immunosuppressive treatment.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        20 to-receive-kidney-transplant patients are randomized, the self-control study protocol is&#xD;
        utilized for each patient as the following.&#xD;
&#xD;
        Under the condition of signed informed consent, for 20 kidney transplant recipients For 20&#xD;
        patients that have been diagnosed with acute rejection on the first visits.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients are suitable for kidney transplant surgeries. Or There is obvious evidence&#xD;
             for acute rejection of the allograft kidneys. The patients have no infectious&#xD;
             complications.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients have failed in the transplant surgeries. Patients have no urine 1 week after&#xD;
             the transplant surgeries. Patients have severe infectious complications after the&#xD;
             transplant surgeries. Or:The patients have infectious complications. The patients have&#xD;
             tumors. The patients are pregnant.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zhang Ming, Doctor</last_name>
    <role>Study Director</role>
    <affiliation>RenJi Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Zhang Ming, Doctor</last_name>
    <phone>13817817827</phone>
    <email>drmingzhang@126.com</email>
  </overall_contact>
  <results_reference>
    <citation>De 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.</citation>
    <PMID>26460048</PMID>
  </results_reference>
  <results_reference>
    <citation>Lo YM, Tein MS, Pang CC, Yeung CK, Tong KL, Hjelm NM. Presence of donor-specific DNA in plasma of kidney and liver-transplant recipients. Lancet. 1998 May 2;351(9112):1329-30. doi: 10.1016/s0140-6736(05)79055-3. No abstract available.</citation>
    <PMID>9643800</PMID>
  </results_reference>
  <verification_date>September 2018</verification_date>
  <study_first_submitted>November 29, 2018</study_first_submitted>
  <study_first_submitted_qc>November 29, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 30, 2018</study_first_posted>
  <last_update_submitted>November 29, 2018</last_update_submitted>
  <last_update_submitted_qc>November 29, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 30, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>DNA acute rejection kidney transplantation</keyword>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03759535
org study id: RenJiH-renal transplantation01
nct id: NCT03759535
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Acute rejection (AR) is still one of the major complications after kidney transplantation.
      The current diagnosis measure for AR is primarily pathological puncture test and hematuria
      biomarker detection, yet due to their inferior performance on timeliness, the allograft
      kidneys usually have been in severe conditions when the diagnoses take place. Donor derived
      cell free DNA (dd-cfDNA) is utilized as a measure for "liquid biopsy", it can predict acute
      rejection at very early periods, and it is easy to operate, with fewer invasive injuries, and
      can reflect related conditions in a timely manner, etc.. This study plans to utilize
      second-generation sequencing technology to systematically evaluate the abundance variations
      of nuclear genome and mitocondria derived dd-cfDNA in the kidney transplant recipients' blood
      and urine, thus it can assist in accumulating more proof for the clinical utilization of
      dd-cfDNA from different sources at the early stages of AR in evidence-based medicine, and lay
      foundation for the development of dd-cfDNA based early-stage rejection detection tools
      afterkidney transplantation surgery.
With the growing development of kidney transplant technologies and immunosuppressive
      therapies, the number of end-stage renal disease patients receiving kidney transplant has
      been increasing. Acute rejection (AR) is one of the main complications for kidney
      transplantation, and AR is the major reason for lowering graft survival rate and for graft
      malfunction, thus the timely detection of AR and early interventions are crucial. The current
      clinical measures for the detection of AR include pathological puncture test and hematuria
      biomarker detection. Yet pathological tests are invasive, limited to sampling errors and the
      existing perception differences among observants, and with other disadvantages such as
      expensiveness, poor patient compliance, and related complications. Hematuria biomarker
      detection is slow in response and low in the sensitivity and specificity for reflecting the
      organs' metabolic index in the diagnosis of acute rejection injury. Though the monitoring of
      immunosuppressant drugs, immune molecules and cytokines in the blood circulation can both
      provide certain value for the evaluation of patients' immune status after organ transplant,
      these factors are not good indicators for the early-stage diagnosis of allograft injury.
      Donor derived cell free DNA (dd-cfDNA) is utilized as a measure for "liquid biopsy", it is
      easy to operate, with less invasiveness, and it can reflect related conditions in a timely
      manner, etc.. This measure can detect the injury degree for allograft, and the index will
      rise before fluctuation reflection of the syndrome and related laboratory indexes, which is
      crucial for the very early-stage diagnosis of allograft acute rejection, and the further
      prevention of allograft injury. In the mean time, dd-cfDNA assumes high utilization value for
      the monitoring of immunosuppressive conditions, and therefore providing instructions for the
      optimization of the immunosuppressive treatment.

      Under the condition of signed informed consent, the study protocols were scheduled as below:

      Self-control study protocol:

      20 to-receive-kidney-transplant patients are randomized, the self-control study protocol is
      utilized for each patient as the following.

      Before the kidney transplant surgery, 1ml of peripheral EDTA anticoagulant from the
      recipients, and 1ml of peripheral EDTA anticoagulant from the donors are collected.

      In 1 week, 2 weeks, 3 weeks' time after the kidney transplant surgeries, 8 to 10 ml of
      peripheral blood from the recipients using cfDNA blood collection tubes, and 10 to 15 ml of
      midstream urine are collected respectively.

      Inclusion criteria:

      *Patients are suitable for kidney transplant surgeries.

      Exclusion criteria:

        -  Patients have failed in the transplant surgeries.

        -  Patients have no urine 1 week after the transplant surgeries.

        -  Patients have severe infectious complications after the transplant surgeries. b, Case
           group: For 20 patients that have been diagnosed with acute rejection on the first
           visits, 8 to 10 ml of EDTA anticoagulant, 10 to 15 ml of midstream urine, 5 ml of saliva
           are collected before the treatment, 1 week and 2 weeks after the adjustment of the
           anti-rejection treatment, 8 to 10 ml of blood using cfDNA blood collection tubes, 10 to
           15 ml of midstream urine, 5 ml of saliva are collected respectively.

      Inclusion criteria:

      Control group:

        -  The allograft kidneys function normally.

        -  The rejection of allograft kidneys are excluded.

        -  The patients have no infectious complications.

      Case group:

        -  There is obvious evidence for acute rejection of the allograft kidneys.

        -  The patients have no infectious complications.

      Exclusion criteria:

        -  The patients have infectious complications.

        -  The patients have tumors.

        -  The patients are pregnant.
observational model: Case-Only
time perspective: Prospective
measure: Renal allograft injury Renal allograft injury
time frame: 2 months
description: serum creatinine level
arm group label: Control group and Case group
description: Control group:
The allograft kidneys function normally. The rejection of allograft kidneys are excluded. The patients have no infectious complications.
Case group:
There is obvious evidence for acute rejection of the allograft kidneys. The patients have no infectious complications.
intervention type: Diagnostic Test
intervention name: Acute rejection
description: Donor derived cell free DNA
arm group label: Control group and Case group
Donor derived cell free DNA (dd-cfDNA) is utilized as a measure for "liquid biopsy", it is
      easy to operate, with less invasiveness, and it can reflect related conditions in a timely
      manner，etc.. This measure can detect the injury degree for allograft, and the index will rise
      before fluctuation reflection of the syndrome and related laboratory indexes, which is
      crucial for the very early-stage diagnosis of allograft acute rejection, and the further
      prevention of allograft injury. In the mean time, dd-cfDNA assumes high utilization value for
      the monitoring of immunosuppressive conditions, and therefore providing instructions for the
      optimization of the immunosuppressive treatment.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 20 Years
maximum age: 60 Years
healthy volunteers: No
last name: Zhang Ming, Doctor
role: Study Director
affiliation: RenJi Hospital
last name: Zhang Ming, Doctor
phone: 13817817827
email: drmingzhang@126.com
citation: De 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.
PMID: 26460048
citation: Lo YM, Tein MS, Pang CC, Yeung CK, Tong KL, Hjelm NM. Presence of donor-specific DNA in plasma of kidney and liver-transplant recipients. Lancet. 1998 May 2;351(9112):1329-30. doi: 10.1016/s0140-6736(05)79055-3. No abstract available.
PMID: 9643800
responsible party type: Sponsor
sharing ipd: Undecided