Mechanistic Evaluation of Treatments for Antibody-Mediated Rejection

• Research type

  Research Study

• Full title

  Mechanistic Evaluation of Treatments for Acute Antibody-Mediated Rejection of the Kidney Transplant (MOT-AMR)

• IRAS ID

  264179

• Contact name

  Candice Roufosse

• Contact email

  c.roufosse@imperial.ac.uk

• Sponsor organisation

  Imperial College London

• Duration of Study in the UK

  7 years, 11 months, 31 days

• Research summary

  The best treatment for kidney failure is a kidney transplant. Transplanted kidneys work for on average 10-15 years. One of the reasons for this is that the body develops antibodies against the transplant, leading to acute antibody mediated rejection (AAMR). We are conducting a clinical trial into treating AAMR with rituximab in UK patients (TAR:GET-1). Patients in the trial will either receive the standard treatment, or the same again plus rituximab. This trial will answer the question: does rituximab lengthen the life of the transplant?
  In the current research proposal, we want to further investigate how treatment works in AAMR. Each patient's B cells produce antibodies with unique characteristics, which in turn lead to variable degrees of severity in the changes in the kidney we see looking down a microscope, and to variable changes in genes switched on and off in the kidney. By exploring these in detail we want to answer 2 questions: 1) Can we predict whether the graft will be lost as a result of AAMR based on the patient’s B cell, antibody and biopsy features?; 2) Can we tell treatment is working by looking at the changes in B cells, antibodies and biopsies before and after treatment?  To answer this we will conduct extra tests on blood samples and the transplant biopsy taken to enrol patients in the trial and samples taken after treatment. We will also offer patients optional extra blood samples and a biopsy at 6 months after treatment. We will look at the results of our analyses before and after treatment, and will compare patients with the standard treatment to those with standard treatment + rituximab. We will analyse if changes in B cells, antibodies and the biopsy explain later differences in how many grafts are still working.

• REC name

  South West - Frenchay Research Ethics Committee

• REC reference

  19/SW/0240

• Date of REC Opinion

  18 Mar 2020

• REC opinion

  Further Information Favourable Opinion