The objective of this study is to determine whether cell-free DNA (cf-DNA) measurement can be used as a biomarker for successful treatment of an acute rejection (AR) episode after kidney transplantation.
A fall in donor cf-DNA level may be a biomarker for successful AR treatment. The goal is to do an exploratory study to determine, in recipients with biopsy-proven AR, whether persistence or elevated levels of donor cf-DNA are associated with ongoing inflammation at the time of exit biopsy; and whether fall in donor cf-DNA level is associated with successful AR treatment.
Measurement of cf-DNA has recently been started for kidney transplant recipients. There will be two groups of patients eligible for this study:
Condition or disease | Intervention/treatment |
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Kidney Transplant Failure and Rejection Kidney Transplant; Complications Kidney Transplant Rejection Transplant; Complication, Rejection Transplant Dysfunction | Genetic: cf-DNA Collection |
Study Type : | Observational |
Estimated Enrollment : | 15 participants |
Observational Model: | Cohort |
Time Perspective: | Prospective |
Official Title: | Cf-DNA Assay During Treatment of Acute Rejection-Pilot Study |
Actual Study Start Date : | June 1, 2019 |
Estimated Primary Completion Date : | December 31, 2021 |
Estimated Study Completion Date : | January 31, 2022 |
Group/Cohort | Intervention/treatment |
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cf-DNA Collection
All patients undergoing kidney allograft biopsy for suspicion of an acute rejection episode will be approached for consent into the study. Patients who consent to the study will have the cf-DNA test drawn at time of biopsy to determine levels of cf-DNA. All consented patients will be followed for biopsy outcomes. Those whose biopsy shows acute rejection leading to treatment will have cf-DNA determination at 2, 4, 6, and 8 weeks post biopsy. Recipients with persistent high cf-DNA levels will undergo repeat biopsy at ~6 weeks after end of treatment per standard of care (this is not performed for purpose of the study, but for clinical care).
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Genetic: cf-DNA Collection
For all consenting recipients undergoing kidney biopsy between 1 and 12 months post-transplant, a single tube of blood will be drawn (at the time of other blood draws so that there is no additional needle stick) to measure cf-DNA. The tube will be shipped to the California lab for determination of donor cf-DNA. For recipients whose biopsy shows AR, a tube of blood will be drawn at 2, 4, 6, and 8 weeks after initiation of anti-rejection treatment and similarly will be shipped to the California lab for determination of cf-DNA. Recipients whose exit biopsy shows ongoing inflammation and receiving additional anti-rejection therapy will have an additional exit biopsy additional cf-DNA determinations. |
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Sampling Method: | Probability Sample |
Inclusion Criteria:
Exclusion Criteria:
Contact: Arthur Matas, MD | 612-625-5151 | matas001@umn.edu | |
Contact: Mary Farnsworth | 612-624-9695 | ewigx005@umn.edu |
United States, Minnesota | |
University of Minnesota | Recruiting |
Minneapolis, Minnesota, United States, 55455 | |
Contact: Arthur Matas, MD 612-625-5151 matas001@umn.edu |
Tracking Information | |||||||||
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First Submitted Date | June 21, 2019 | ||||||||
First Posted Date | July 15, 2019 | ||||||||
Last Update Posted Date | April 29, 2021 | ||||||||
Actual Study Start Date | June 1, 2019 | ||||||||
Estimated Primary Completion Date | December 31, 2021 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures |
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Original Primary Outcome Measures | Same as current | ||||||||
Change History | |||||||||
Current Secondary Outcome Measures |
Number of participants who return to baseline measured donor cf-DNA concentrations [ Time Frame: 8 weeks ] Number of patients for whom a baseline of donor cf-DNA has been ascertained through monitoring prior to acute rejection and who return to baseline cf-DNA after treatment.
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Original Secondary Outcome Measures | Same as current | ||||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
Descriptive Information | |||||||||
Brief Title | Cf-DNA Assay During Treatment of Acute Rejection | ||||||||
Official Title | Cf-DNA Assay During Treatment of Acute Rejection-Pilot Study | ||||||||
Brief Summary |
The objective of this study is to determine whether cell-free DNA (cf-DNA) measurement can be used as a biomarker for successful treatment of an acute rejection (AR) episode after kidney transplantation. A fall in donor cf-DNA level may be a biomarker for successful AR treatment. The goal is to do an exploratory study to determine, in recipients with biopsy-proven AR, whether persistence or elevated levels of donor cf-DNA are associated with ongoing inflammation at the time of exit biopsy; and whether fall in donor cf-DNA level is associated with successful AR treatment. Measurement of cf-DNA has recently been started for kidney transplant recipients. There will be two groups of patients eligible for this study:
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Detailed Description |
Significance of Research Question/Purpose: A kidney transplant biopsy is the gold standard for making a diagnosis at the time of graft dysfunction. However, there are risks associated with a transplant biopsy (e.g., hematuria, clots within the collecting system, bleeding, hematoma within the kidney, urine leak, and rarely AKI and/or graft loss). Recently, a blood test has been developed which distinguishes donor and recipient circulating cf-DNA. Using this methodology, circulating cf-DNA is amplified, then using a panel of markers, 2 DNA peaks can be observed - a high peak for the recipient DNA and a very low peak for the donor (importantly, this is not genetic testing; only high and low peaks are identified). When cf-DNA is measured at the time of a kidney biopsy for graft dysfunction, an elevated donor cf-DNA level - compared to that seen in a cohort without inflammation - can be seen in recipients with an acute rejection (AR) episode. Data, to date, suggests that if >1% of cf-DNA is donor derived, there is likely graft inflammation. Currently, there are ongoing studies to determine if sequential measurement of cf-DNA in the same recipient will show elevated donor cf-DNA levels earlier than a serum creatinine rise, thus potentially allowing earlier detection and treatment of AR episodes. Serum creatinine level is used as a marker for successful treatment of an acute rejection episode. However, creatinine level is an insensitive marker of response to treatment of both cellular and antibody mediated rejection. Studies in which biopsies are done at the end of "presumed" successful rejection treatment show that some patients whose creatinine level returned to baseline have ongoing inflammation. Unless additional anti-rejection treatment is given, this incomplete treatment leads to increased risk for donor-specific antibody formation and graft failure. As a consequence, the investigators (the U of MN Kidney Transplant Program) are now doing routine "exit" biopsies for patients treated for acute rejection episodes and whose serum creatinine level returns to baseline. The investigators have always done biopsies in patients whose creatinine level did not return to baseline. The "exit" biopsy is done at ~6 weeks after completion of rejection treatment. If the exit biopsy shows ongoing inflammation, additional rejection treatment is considered. It would be ideal to have a noninvasive marker for successful rejection treatment. The objective of this study is to determine whether cell-free DNA (cf-DNA) measurement can be used as a biomarker for successful treatment of an acute rejection (AR) episode after kidney transplantation. The addition of cf-DNA testing would have two potential benefits:
Preliminary Data:
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Study Type | Observational | ||||||||
Study Design | Observational Model: Cohort Time Perspective: Prospective |
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Target Follow-Up Duration | Not Provided | ||||||||
Biospecimen | Retention: Samples With DNA Description:
cell-free DNA
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Sampling Method | Probability Sample | ||||||||
Study Population | Adult kidney transplant recipients undergoing transplant biopsy between 1 and 12 months post-transplant because of graft dysfunction. | ||||||||
Condition |
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Intervention | Genetic: cf-DNA Collection
For all consenting recipients undergoing kidney biopsy between 1 and 12 months post-transplant, a single tube of blood will be drawn (at the time of other blood draws so that there is no additional needle stick) to measure cf-DNA. The tube will be shipped to the California lab for determination of donor cf-DNA. For recipients whose biopsy shows AR, a tube of blood will be drawn at 2, 4, 6, and 8 weeks after initiation of anti-rejection treatment and similarly will be shipped to the California lab for determination of cf-DNA. Recipients whose exit biopsy shows ongoing inflammation and receiving additional anti-rejection therapy will have an additional exit biopsy additional cf-DNA determinations. |
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Study Groups/Cohorts | cf-DNA Collection
All patients undergoing kidney allograft biopsy for suspicion of an acute rejection episode will be approached for consent into the study. Patients who consent to the study will have the cf-DNA test drawn at time of biopsy to determine levels of cf-DNA. All consented patients will be followed for biopsy outcomes. Those whose biopsy shows acute rejection leading to treatment will have cf-DNA determination at 2, 4, 6, and 8 weeks post biopsy. Recipients with persistent high cf-DNA levels will undergo repeat biopsy at ~6 weeks after end of treatment per standard of care (this is not performed for purpose of the study, but for clinical care).
Intervention: Genetic: cf-DNA Collection
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Publications * | Not Provided | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status | Recruiting | ||||||||
Estimated Enrollment |
15 | ||||||||
Original Estimated Enrollment | Same as current | ||||||||
Estimated Study Completion Date | January 31, 2022 | ||||||||
Estimated Primary Completion Date | December 31, 2021 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender |
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Ages | 18 Years and older (Adult, Older Adult) | ||||||||
Accepts Healthy Volunteers | No | ||||||||
Contacts |
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Listed Location Countries | United States | ||||||||
Removed Location Countries | |||||||||
Administrative Information | |||||||||
NCT Number | NCT04019353 | ||||||||
Other Study ID Numbers | SURG-2018-27247 | ||||||||
Has Data Monitoring Committee | No | ||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement |
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Responsible Party | University of Minnesota | ||||||||
Study Sponsor | University of Minnesota | ||||||||
Collaborators | Not Provided | ||||||||
Investigators | Not Provided | ||||||||
PRS Account | University of Minnesota | ||||||||
Verification Date | April 2021 |