NOMINATE/ Minimisation of Immunosuppression in Kidney Transplantation

• Status: Not yet recruiting
• Trial end date: 2027-02-20
• Target enrollment: 0
• Participant gender: All

Summary

Kidney transplantation provides the optimal form of kidney replacement therapy for the majority of people with end-stage kidney disease, and has now become the commonest form of kidney replacement therapy. However, donor and recipient demographics have changed considerably over the past few decades: increasingly older donor kidneys are transplanted into progressively older recipients with greater comorbidities. Increasing age remains a major risk factor for death after kidney transplantation, with the commonest causes of deaths for recipients aged 70 and over being cardiovascular, infection, and malignancies. Immunosuppressant drugs which are critical for the maintenance of the transplanted organ can contribute to increased morbidity and mortality, by direct effects or through lowered immunity predisposing to infection. Cytomegalovirus (CMV) is one of the most common opportunistic infections that affects renal transplant patient outcome and can be monitored prospectively. Hence, minimising immunosuppression, especially in older recipients, may result in better graft and patient outcomes as many side-effects are dose dependant. However, to date drug doses have never been adjusted based on age, despite significant changes that occur to immune responsiveness as patients grow older. In addition , researchers have not had a biomarker to help define appropriate immunosuppressive levels for each individual.

The investigators therefore aim to study the effect of reducing the target immunosuppression drug levels( of tacrolimus and mycophenolate) in kidney transplant recipients >60 years, using CMV viraemia as a main outcome measure, and investigating rates of rejection and development of de novo donor-specific anti-HLA antibodies. The investigators will assess the clinical utility of donor-derived cell free DNA (dd-cfDNA) as a means to guide immunosuppression minimisation. The investigators propose that the use of lower doses of immunosuppression will result in fewer infection-related complications, translating to improved patient outcomes. The research will be carried out in kidney transplant centres where prospective CMV monitoring is practiced.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University College, London
• Collaborator: Natera, Inc.
• Treatments: Mycophenolic Acid; Tacrolimus

Criteria

Inclusion Criteria:

1. Participant must be first time adult recipients of either a deceased or living donor kidney transplant.

2. Participant must be a recipient of a single organ transplant only.

3. Participant must be above the age of 60 years.

4. Participant must have a negative screen for donor-specific antibody prior to transplantation (MFI<2000).

Exclusion Criteria:

1. Recipients of a transplant who are highly sensitised (cRF >85%).

2. Inability to participate in frequent monitoring of renal transplant function and clinical visits (every 4 weeks) during dd-cfDNA monitoring and IS minimisation.

3. Participants with immune-mediated renal disease in which IS minimisation is inadvisable.

4. EBV negative recipient (as IS minimisation is part of standard protocol)

5. Inability to comply with study directed treatment