The ADOPTION Study
Research type
Research Study
Full title
AZD1656 in Transplantation with Diabetes tO PromoTe Immune TOleraNce
IRAS ID
252155
Contact name
Kieran McCafferty
Contact email
Sponsor organisation
Queen Mary University London
Eudract number
2019-001587-30
Duration of Study in the UK
2 years, 5 months, 1 days
Research summary
Type 2 diabetes is the most common cause of end-stage renal failure in the UK. Kidney transplantation is widely held to be the optimal form of renal replacement therapy, leading to improved survival and quality of life.
Transplantation can worsen diabetic control, which promotes infections and leads to poorer outcomes. These effects are most pronounced within the early post-transplant period.
Glucokinase lowers blood glucose levels by increasing insulin secretion by the pancreas and by increasing the uptake of glucose by the liver. As a result, glucokinase activators such as AZD1656 have been investigated as novel anti-diabetic agents. Across clinical studies, AZD1656 has been well tolerated and no safety concerns have been raised. Although the long-term anti-diabetic effect of AZD1656 has been found to wear off after several months, a shorter course may be beneficial in controlling glucose levels of diabetic patients immediately after renal transplantation when sugars are highest. In addition, AZD1656 may have other benefits post transplantation due to its effects on immune function.
Regulatory T cells (Tregs) are a population of white blood cells which regulate immune responses. They are associated with transplant acceptance and high levels of these cells may improve transplant survival and function. Preliminary data suggests that glucokinase activation in Tregs stimulates their migration into inflamed tissues; which may lead to improved outcomes for transplant patients
We propose an exploratory phase 2 study, examining the efficacy and safety of three months’ treatment with AZD1656 100mg or placebo twice daily in 50 patients with diabetes undergoing renal transplantation in a tertiary renal unit. This is a randomised double-blind trial. We will measure the effect on Tregs, transplant function and diabetic control.
REC name
East of England - Cambridge East Research Ethics Committee
REC reference
19/EE/0209
Date of REC Opinion
26 Jul 2019
REC opinion
Further Information Favourable Opinion