Expanding the Scope of Post-transplant HLA-specific Antibody Detection and Monitoring in Renal Transplant Recipients

NCT06025240 | Recruiting

• 1 other identifier: LHS0037
• Study Type: observational
• Target: 282
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess a new test to detect antibodies which may form following kidney transplant. These antibodies can be difficult to detect as they do not cause any symptoms but can lead to kidney damage. A new blood test will be performed alongside existing antibody tests to see how well the test functions in comparison and to see how well it is able to distinguish between inflammation caused by antibodies and other sorts of inflammation such as a urinary tract infection. The investigators also want to determine whether it is predictable whom will develop antibodies after a transplant and use these results to change the current way patients are monitored for antibodies after receiving a transplant. In addition to this, the investigators want to establish if patients over 60 years of age are relatively protected against immunological events such as rejection compared to patients who are under 60 years of age. The results could potentially lead to using a different immunosuppression regime based on which population age group patients belong to and lowering the risks associated with these drugs.

Conditions

Kidney Transplant; Renal Transplant Failure; Kidney Transplant Rejection; Frailty; Kidney Transplant; Complications; Transplant Dysfunction; Diagnosis; Renal Transplant

Keywords

kidney transplant; novel biomarkers; post-transplant antibodies; HLA-specific antibodies; donor specific antibodies; transplant in older age; machine learning; predictive models; rejection

Outcome Measures

Primary Outcomes (3)

• dd-cf DNA

  Occurrence of a positive cell free DNA test in high-risk post-transplant patients at 6-12 months

  6-12 months post-transplant

• Immunological events in older age

  Frequency of the development of immunological events in the over 60s versus \<60 cohorts

  through study completion, an average of 1 year

• Longitudinal DSA monitoring

  Frequency of development of de novo HLA specific antibody in the 1st year following transplantation in patients previously unsensitised.

  through study completion, an average of 1 year

Secondary Outcomes (6)

• Occurrence of UTIs, viral reactivation and structural transplant abnormalities in high-risk post-transplant patients at 6-12 months

  6-12 months

• Association of cell free DNA result and any identified pathology (DSA, UTI, viral infection)

  through study completion, an average of 1 year

• Comparison of graft and patient survival to 12 months in the over 60s and <60

  through study completion, an average of 1 year

• Comparison of renal function, viral reactivation, readmission and reoperation rates between the 2 age groups (over 60s and <60)

  through study completion, an average of 1 year

• Comparison of post-transplant complications (utilising the Clavien-Dindo classification of surgical complications) between patients developing de novo HLA specific antibody and those who do not, using machine learning models

  through study completion, an average of 1 year

Study Arms (3)

cf-DNA arm

Participants will be recruited on the basis of having received a renal transplant within the last 6-12 months which has been deemed high risk. They will be identified from a database currently held within the renal transplant unit by members of the direct care team. They will be approached at a routine outpatient appointment for inclusion into the study and testing can be performed at their time of routine post-transplant testing where they will undergo blood (dd-cf DNA NGS assay), standard of care tests: blood count, renal profile, donor specific antibodies (DSA) sample, BK virus PCR, CMV PCR, urine testing and an ultrasound of the graft.

Diagnostic Test: cf-DNA

Immunological Events following renal transplant in older age

The renal transplant population will be divided on the basis of age into two cohort: ≥60 and \<60. All renal transplant patients are regularly followed up in the outpatient clinic where blood and urine tests are collected, and clinical evaluations are performed. It is not foreseen that this study will necessitate any additional hospital visits or testing above and beyond the usual standard of care. Serum samples are taken at the time intervals indicated for routine storage and we will simply use those samples for HLA testing (either screening alone or screening and single antigen bead testing if screening yields a positive result).

Diagnostic Test: Immunological Events following renal transplant in older age

Determining Predictive Models for Post-transplant HLA-specific Antibody Formation

A subset of the cohort of recruits to the immunological factors in older age study will be used to determine machine learning algorithms of predictive factors for the development of de novo donor specific antibody. Only patients who were unsensitised prior to the kidney transplant will be included into the study because prior sensitisation makes determining de novo specificities much harder. The follow up period will be set at 1 year to synchronise with the older age study.

Other: Determining Predictive Models for Post-transplant HLA-specific Antibody Formation

Interventions

cf-DNA DIAGNOSTIC_TEST

In addition to the standard of care tests, participants will have an additional blood sample (dd-cf DNA). A cohort study patients who have undergone high immunological risk kidney transplant at our centre defined as a re-transplant, where the cRF is \>20% or where there is a level 4 HLA-mismatch. We will take a single plasma sample for dd-cfDNA testing at 6-12 months post-transplant and pair this with an assessment of renal function (creatinine, eGFR), MSU, BK and CMV PCR, single antigen bead (SAB) monitoring of HLA-specific antibodies and allograft USS.

Also known as: donor derived cell-free DNA (dd-cf DNA)

cf-DNA arm

Immunological Events following renal transplant in older age DIAGNOSTIC_TEST

Determine the overall frequency of immunological events and de novo HLA specific antibody formation in the \<60 and \>60 age population. Standard of care test taken at the different time intervals for routine storage. We will use those samples for HLA testing (either screening alone or screening and single antigen bead testing if screening yields a positive result).

Also known as: Longitudinal DSA monitoring

Immunological Events following renal transplant in older age

Determining Predictive Models for Post-transplant HLA-specific Antibody Formation OTHER

A machine learning model will be developed in Python using a range of pre- and post-transplant variables to determine a predictive model for de novo HLA-specific antibody following renal transplant.

Also known as: Machine learning algorithms

Determining Predictive Models for Post-transplant HLA-specific Antibody Formation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

1. cf-DNA arm: Patients who have undergone a "high risk" renal transplant in our unit within the last 6-12 months will be retrospectively recruited to the study. 2. Older Age Immunological Events: Post-transplant patients prospectively recruited, irrespective of age, undergoing transplant to determine the overall frequency of immunological events and de novo HLA specific antibody formation. We will collect data on clinical outcomes and would look to compare the \<60s with those 60 or older looking for a difference in immunological events beteween the 2 groups. 3. Predictive models: A subset of the cohort of recruits to the immunological factors in older age study will be used to determine machine learning algorithms of predictive factors for the development of de novo donor specific antibody.

You may qualify if:

• cf-DNA arm:
• Adult patients transplanted within 6-12 months (retrospective recruitment)
• Patients admitted for renal transplant or within the first 6 months following transplant (prospective recruitment)
• Patients must have capacity to provide informed consent
• Patients must have received a high-risk transplant defined as level 4 mismatch, cRF \>20, second or subsequent transplant, ABO or HLA incompatible
• Older Age Immunological Events:
• \- Any adult patient with capacity undergoing, or within 72 hours of, a renal transplant
• Predictive models:
• Any adult patient with capacity undergoing, or within 72 hours of, a renal transplant
• Unsensitized pre-transplant

You may not qualify if:

• cf-DNA arm:
• Transplanted for longer than 12 months;
• Low risk transplants;
• Patients lacking capacity;
• Older Age Immunological Events:
• Patients lacking capacity
• Patients transplanted longer than 2 weeks
• Predictive models:
• Sensitised patients
• Patients lacking capacity
• Patients transplanted longer than 2 weeks

Sponsors & Collaborators

• Liverpool University Hospitals NHS Foundation Trust: lead
• Kidney Research United Kingdom: collaborator

Study Sites (1)

Liverpool University Hospitals NHS Foundation Trust

Liverpool, Merseyside, L7 8YE, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Donor-derived cell-free DNA next generation sequencing assay (dd-cfDNA) Donor Specific Antibody (screen +/- single antigen bead) (DSA)

MeSH Terms

Conditions

Frailty; Disease; Rejection, Psychology

Interventions

Machine Learning Algorithms

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Social Behavior; Behavior

Intervention Hierarchy (Ancestors)

Algorithms; Mathematical Concepts

Study Officials

• Petra M Goldsmith, MBBChir PhD FRCS

  Liverpool University Hospitals NHS Foundation Trust

  STUDY DIRECTOR

• George E Nita, MBChB MSc MRCSEd

  Liverpool University Hospitals NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

George E Nita, MBChB MSc MRCSEd

CONTACT

01517062000; george.nita@liverpoolft.nhs.uk

Petra M Goldsmith, MBBChir PhD FRCS

CONTACT

01517055550; petra.goldsmith@liverpoolft.nhs.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2023
• First Posted: September 6, 2023
• Study Start: October 13, 2023
• Primary Completion: October 13, 2025
• Study Completion (Estimated): October 13, 2026
• Last Updated: August 30, 2024

Record last verified: 2024-04

Locations

GB (1)