LITE, V1
Research type
Research Study
Full title
Low-dose IL-2 to expand endogenous regulatory T cells and to achieve tolerance in liver transplantation
IRAS ID
215874
Contact name
Alberto Sanchez-Fueyo
Contact email
Sponsor organisation
King's College London
Eudract number
2017-000177-37
Clinicaltrials.gov Identifier
Duration of Study in the UK
3 years, 9 months, 0 days
Research summary
Following liver transplantation patients need to receive powerful drugs (known as immunosuppressants), to prevent rejection. These drugs are usually administered lifelong, which results in important side effects. This the main reason why ultimately transplanted patients die more frequently than non-transplanted healthy individuals. Not all liver transplant patients, however, require lifelong immunosuppressive medication. Some of them develop a phenomenon known as operational tolerance and can discontinue this medication without rejecting. In tolerant patients the withdrawal of anti-rejection medication could increase their survival and improve their quality of life. Unfortunately this phenomenon usually develops in elderly recipients and several years after transplantation. To maximize the benefit derived from stopping these drugs, there is a need to find ways to intentionally create tolerance in young recipients in whom accumulated drug toxicity has not yet occurred.
Our studies have revealed that successful stopping of the immunosuppressants is associated with a response of regulatory T cells (Tregs). This suggests that short-term increase of Treg numbers and/or function at the time of stopping the immunosuppressants may increase tolerance in patients who do not spontaneously develop it. IL-2 is a cytokine (a type of signalling cell) that is essential for the optimal development, survival and function of Tregs. Clinical studies have shown that low-dose IL-2 expands Tregs and is safe and efficacious in patients with autoimmunity or GVHD. In these studies, Treg frequency increased up to 2 to 8-fold without significant changes in the number of effector T cells. Our objective is to investigate if administration of a short-course of low dose IL-2 to liver transplant recipients can allow them to stop their drugs. We propose a phase IV, safety and efficacy, prospective, single-arm clinical trial in which liver recipients <50 years old and 2-6 years after transplantation will receive IL-2 and gradually discontinue the immunosuppression medication.REC name
London - Central Research Ethics Committee
REC reference
17/LO/1014
Date of REC Opinion
24 Jul 2017
REC opinion
Further Information Favourable Opinion