Improving KIdney Transplantation with Cellular Therapy Study

NCT06243289 | Terminated

• 1 other identifier: ikitcat
• Study Type: observational
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

The i-KITCaT study aims to harness cellular therapies to favourably alter the immunological response to in AKI in transplantation. Kidney transplantation offers the best survival and quality of life outcomes for patients with end-stage kidney disease but requires life-long immunosuppression. Efforts to increase the donor organ pool means accepting kidneys which have been subjected to medical and surgical factors culminating in acute kidney injury (AKI). There is no treatment to modify the maladaptive injury process following an AKI insult, and this subjects the new kidney to increased risk of needing dialysis in the first 7 days of transplantation, rejection, and shortened transplant survival. Tolerogenic dendritic cells (TolDC) are currently used in phase I/II clinical trials and are safe for patients receiving a kidney transplant from the same donor as these cells. These trials focus on transplant tolerance, but we will re-purpose TolDCs to favorably alter the disease course following AKI and limit injury following transplantation. Furthermore, if the patient's own cells (rather than from a third-party donor) can be used, this avoids supply limitations and potential sensitization risk. We will compare the functional characteristics of TolDC generated from control (healthy) and kidney disease (chronic kidney disease (CKD), dialysis and transplantation).

Conditions

Immune Tolerance; Kidney Transplant Rejection

Outcome Measures

Primary Outcomes (1)

• Tolerogenic dendritic cells

  Test flow cytometry, cytokine assays and mixed lymphocyte reaction to show tolerogenic potential of ex-vivo tolerogenic dendritic cells derived from peripheral blood monocytes of donors with and without kidney disease

  7 days post ex-vivo culture

Secondary Outcomes (1)

• Transcriptomic differences in tolerogenic dendritic cells derived from healthy and kidney disease donors

  12-months from culture/ex-vivo generation

Study Arms (2)

Healthy participants

Volunteers with no kidney disease, autoimmune disease or major cardiovascular comorbidities

Other: Tolerance induction

Participants with kidney disease

Includes patient with chronic kidney disease, dialysis or functioning transplant

Other: Tolerance induction

Interventions

Tolerance induction OTHER

Exposure of peripheral blood mononuclear cells extracted from donated patient blood to a combination of vitamin D3 and interleukin 10 to test whether tolerogenic dendritic cells can be generated and have the same functional capacity between donors with and without kidney disease (exposure of PBMC to the uremic environment)

Healthy participants; Participants with kidney disease

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Study groups * Healthy control (eGFR \> 90 ml/min/1.73m2 and no known medical issues) * Kidney disease with any of the following * CKD stage 5 (eGFR \< 15 ml/min/1.73m2 from any cause) * Dialysis patients (haemodialysis and peritoneal dialysis) * Transplant patients (\>12-months post-transplant and without prior rejection)

You may qualify if:

• able to consent, able to provide blood sample

You may not qualify if:

• unable to consent, life-expectancy less than 6 months

Sponsors & Collaborators

• Western Sydney Local Health District: lead

Study Sites (1)

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood collected for PBMC and DNA. DNA will be bio-banked for future renal related research.

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: CPI, Nephrologist and Transplant Physician

Study Record Dates

• First Submitted: January 28, 2024
• First Posted: February 6, 2024
• Study Start: September 19, 2023
• Primary Completion: February 26, 2025
• Study Completion: February 26, 2025
• Last Updated: March 28, 2025

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)