Donor-derived Cell-free DNA for Early Diagnosis of Antibody-mediated Rejection (cfDNA-DSA)

January 17, 2025 updated by: Klemens Budde, Charite University, Berlin, Germany

Donor-derived Cell-free DNA for Early Diagnosis of Antibody-mediated Rejection in Kidney Transplant Recipient with Donor-specific Antibodies

Patients after kidney transplantation who develop donor-specific antibodies (DSA) are at high risk for antibody-mediated rejection (ABMR). Donor-derived cell-free DNA (dd-cfDNA) levels have been shown to be increased in patients with active or chronic active ABMR. This study aims to evaluate if repeated analysis of dd-cfDNA in patients with DSA and kidney allograft biopsy which is triggered by increased levels of dd-cfDNA can lead to early diagnosis of active or chronic active ABMR among these patients.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Berlin, Germany, 10117
        • Charité-Universitätsmedizin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • patients 18 years or older
  • patients provided written informed consent
  • patients after kidney transplantation
  • functioning kidney allograft, at least after 180 days after last transplantation
  • estimated glomerular filtration rate above 20 ml/min/1.73m^2
  • detection of DSA

Exclusion Criteria:

  • patients younger than 18 years
  • patients unable or did not provide written informed consent
  • pregnant or breastfeeding persons
  • patients with increased bleeding risk
  • patients with multi-organ transplantation
  • patients who underwent kidney allograft biopsy after first detection of DSA
  • biopsy-proven antibody-mediated rejection
  • participation in another interventional clinical trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Intervention
Additionally to standard of care, measurements for donor-derived cell-free DNA (dd-cfDNA) are performed at months 0, 1, 3, 6, 9, and 12. If absolute levels of dd-cfDNA are > 50 copies/ml, the patients receive a kidney allograft biopsy. Additionally, kidney allograft biopsies are performed according to standard of care as determined by the treating physicians.
Procedure: Kidney allograft biopsy depending on donor-derived cell-free DNA levels
Kidney allograft biopsy is performed, when absolute levels of donor-derived cell-free DNA are above 50 copies/ml
No Intervention: Control
Additionally to standard of care, measurements for donor-derived cell-free DNA (dd-cfDNA) are performed at months 0, 1, 3, 6, 9, and 12. These measurements are not used to guide kidney allograft biopsies. Those are performed according to standard of care as determined by the treating physicians.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Time from study inclusion to diagnosis of antibody-mediated rejection
Time Frame: 12 months after inclusion
Time from study inclusion date to biopsy-proven diagnosis of active or chronic active antibody-mediated rejection
12 months after inclusion

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Sensitivity of absolute dd-cfDNA for detection of ABMR
Time Frame: 12 Months
Sensitivity of dd-cfDNA > 50 copies/ml to predict the occurence of active or chronic active ABMR in patients with DSA.
12 Months
Specificity of absolute dd-cfDNA for detection of ABMR
Time Frame: 12 Months
Specificity of dd-cfDNA > 50 copies/ml to predict the occurence of active or chronic active ABMR in patients with DSA.
12 Months
Receiver operating characteristics (ROC) analysis of absolute dd-cfDNA for detection of ABMR
Time Frame: 12 Months
ROC analysis for dd-cfDNA to predict the occurence of active or chronic active ABMR in patients with DSA.
12 Months
Sensitivity of intraindividual dd-cfDNA changes for detection of ABMR
Time Frame: 12 Months
Sensitivity of dd-cfDNA increase of > 25% to predict the occurence of active or chronic active ABMR in patients with DSA.
12 Months
Sensitivity of combined dd-cfDNA criterion for detection of ABMR
Time Frame: 12 Months
Sensitivity of the combination of "dd-cfDNA increase of > 25%" OR "absolute dd-cfDNA > 50 copies/ml" to predict the occurence of active or chronic active ABMR in patients with DSA.
12 Months
Clinical Outcome - estimated glomerular filtration rate (eGFR) 12 Months
Time Frame: 12 Months
Difference between eGFR decline after 12 months between control group and intervention group.
12 Months
Clinical Outcome - eGFR 24 Months
Time Frame: 24 Months
Difference between eGFR decline after 24 months between control group and intervention group.
24 Months
Clinical Outcome - albuminuria 12 Months
Time Frame: 12 Months
Difference between albuminuria after 12 months between control group and intervention group.
12 Months
Clinical Outcome - albuminuria 24 Months
Time Frame: 24 Months
Difference between albuminuria after 24 months between control group and intervention group.
24 Months
Clinical Outcome - Death-censored Graft Failure 12 Months
Time Frame: 12 Months
Difference in Death-censored Graft Failure after 12 months between control group and intervention group.
12 Months
Clinical Outcome - Death-censored Graft Failure 24 Months
Time Frame: 24 Months
Difference in Death-censored Graft Failure after 24 months between control group and intervention group.
24 Months
Clinical Outcome - Mortality 12 Months
Time Frame: 12 Months
Difference in Mortality after 12 months between control group and intervention group.
12 Months
Clinical Outcome - Mortality 24 Months
Time Frame: 24 Months
Difference in Mortality after 24 months between control group and intervention group.
24 Months
Clinical Outcome - Severe Infection 12 Months
Time Frame: 12 Months
Difference in occurence of severe infections (hospitalization, organ failure, death) during 12 months between control group and intervention group.
12 Months
Clinical Outcome - Severe Infection 24 Months
Time Frame: 24 Months
Difference in occurence of severe infections (hospitalization, organ failure, death) during 24 months between control group and intervention group.
24 Months
Adverse Events of Kidney Transplant Biopsy
Time Frame: 12 Months
Occurence of Complications from Kidney Transplant Biopsies, including Duration and potential therapy to treat the adverse event.
12 Months
Rate of ABMR
Time Frame: 12 Months
Number of biopsy proven active or chronic active ABMR in the cohort.
12 Months
DSA Levels 0 Months
Time Frame: at inclusion
Mean fluorescence intensity of immunodominant DSA
at inclusion
DSA Levels 12 Months
Time Frame: 12 months
Mean fluorescence intensity of immunodominant DSA at 12 months
12 months
DSA Levels 24 Months
Time Frame: 24 months
Mean fluorescence intensity of immunodominant DSA at 24 months
24 months
Immunosuppressive Regimen
Time Frame: 24 months
Report of immunosuppressive medication at the following time points: 0,1,3,6,9,12,24 months, changes of medication, additional therapies such as plasmapheresis, or experimental therapies.
24 months
Time from first DSA occurrence to diagnosis of antibody-mediated rejection
Time Frame: 12 months after inclusion
Time from first DSA occurrence to biopsy-proven diagnosis of active or chronic active antibody-mediated rejection
12 months after inclusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Charite University, Berlin, Germany

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Klemens Budde, MD, Charite University, Berlin, Germany

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 18, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 9, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 18, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 18, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 21, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 17, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2025

More Information

Terms related to this study

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CHA-NTX-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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