Kidney transplant Urological and Genital Diseases
Conditions
Interventions
Current interventions as of 23/09/2020:
Participating living donor renal transplant recipients will be randomised on a 1:1 basis to either Treg cell infusion (intervention) or standard care (control).
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Age
18 Years to 110 Years
Inclusion criteria
Inclusion criteria: Kidney recipient inclusion criteria: 1. Chronic renal insufficiency necessitating kidney transplantation and approved to receive a kidney allograft from a living donor 2. Willing and able to give informed consent for participation in the trial 3. Aged 18 years or above 4. In the Investigator’s opinion, is able and willing to comply with all trial requirements 5. Able to commence the immunosuppressive regimen at the protocol-specified time point 6. Female participants of child bearing potential and male participants whose partner is of childbearing potential must be willing to ensure that they or their partner use highly effective contraception during the trial 7. Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the trial Kidney donor inclusion criteria: 1. Eligible for live kidney donation 2. Aged at least 18 years 3. ABO blood group compatible with the organ recipient 4. Willing to provide personal, medical and biological data for the trial analysis 5. Willing and able to provide a blood sample for the immune monitoring assays 6. Willing and able to give informed consent for participation in the trial
Exclusion criteria
Exclusion criteria: Kidney recipient exclusion criteria: 1. Patient has previously received any tissue or organ transplant 2. Known contraindication to the protocol-specified treatments or medications 3. ABO blood group incompatible with donor 4. Calculated reaction frequency (CRF) of >40% within 6 months prior to transplant 5. Previous treatment with any desensitisation procedure (with or without IVIg) 6. Concomitant malignancy or history of malignancy within 5 years prior to planned study entry (excluding successfully treated non-metastatic basal or squamous cell carcinomas of the skin) 7. Serologically positive for anti-HIV-1/2 Ab, HbsAg, anti-HBcAb, antiHCV Ab, anti-HTLV-1/2 Ab or syphilis (treponema palladium) 8. Significant liver disease, defined as persistently elevated ALT levels >3 x upper limit of normal range (ULN) 9. Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial 10. Participation in another clinical trial during the study or within 28 days prior to planned study entry 11. Female participant who is pregnant, lactating or planning pregnancy during the course of the trial 12. Psychological, familial, sociological, or geographical factors potentially hampering compliance with the study protocol and follow-up visit schedule 13. Any form of substance abuse, psychiatric disorder, or other condition that, in the opinion of the investigator, may invalidate communication with the investigator and/or designated personnel Kidney donor exclusion criteria: 1. Exposure to any investigational agents at the time of kidney donation, or within 28 days prior to kidney donation 2. Any form of substance abuse, psychiatric disorder, or other condition that, in the opinion of the Investigator, may invalidate communication with the Investigator designated personnel 3. Is a paired exchange donor 4. Is an altruistic donor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of biopsy-confirmed acute rejection (BCAR) in the 6 to 18-month period post-transplantation. A 9 month protocol biopsy will be performed in all participants including the control arm to allow a histological comparison of the impact of Treg therapy in the treatment arm. Any other biopsies performed during follow-up will be at the discretion of the responsible clinician and will be deemed ‘for-cause’. All biopsies will be reviewed and reported by the study pathologist using the Banff criteria. | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 23/09/2020: Measured over 18 months post-transplant: 1. Time to first biopsy-confirmed acute rejection episode will be measured in days 2. Severity of acute rejection episodes will be based on histological scoring according to the Banff criteria and degree of renal recovery following treatment 3. Incidence of graft loss due to rejection 4. Renal transplant function will be assessed by estimated glomerular filtration rate (eFGR) using the CKD-EPI equation 5. Patient survival 6. Incidence of adverse events to include: 6.1. Incidence of drug-related adverse events 6.2. Incidence of identified serious and/or opportunistic infections (including CMV, EBV and polyoma (BK) virus) 6.3. Incidence of neoplasia 6.4. Incidence of autoimmune disorders 6.5. Incidence of anaemia, cytopaenia and biochemical disturbances unrelated to kidney function 7. Total immunosuppression burden at 18 months post-transplantation will be defined by number of immunosuppressive agents, dose of immunosuppressive agents and serum tacrolimus level (measured in nanograms per ml). This will include assessment of the proportion of patients taking tacrolimus monotherapy 8. Chronic allograft nephropathy on renal transplant biopsies will be measured by the degree of interstitial fibrosis and tubular atrophy (IF/TA) as assessed by the study pathologist on protocol biopsies taken at 9 months post-transplant 9. Patient-reported outcomes measured using SF-36 and EQ-5L-5D questionnaires Exploratory outcome measures: 1. Immune monitoring will be assessed formally at 2 weeks pre-transplant, day+4 and weeks 1, 2, 4, 12, 38, 43, 51 and 78 post-transplant. Patients in the treatment arm will also be analysed at 22 weeks post-transplant. Outcomes will include: 1.1. Cell phenotype analysis of peripheral blood 1.2. T cell functional assays against donor and third-party antigens 1.3. Serum cytokine analysis and third-party antigen analysis 1.4. Gene expression and RNA sequencing an | — |
Countries
England, United Kingdom
Outcome results
None listed