Abstract: PUB315
ADOPTION Study Protocol: AZD1656 in Transplantation With Diabetes to Promote Immune Tolerance
Session Information
Category: Transplantation
- 2002 Transplantation: Clinical
Authors
- Allan, Michelle Elizabeth, Barts Health NHS Trust, London, London, United Kingdom
- Fan, Stanley, Barts Health NHS Trust, London, London, United Kingdom
- Marelli-Berg, Federica M., Queen Mary University of London, London, London, United Kingdom
- Yaqoob, Muhammad Magdi, Barts Health NHS Trust, London, London, United Kingdom
- Mccafferty, Kieran, Barts Health NHS Trust, London, London, United Kingdom
Background
Transplant recipients with pre-existing T2DM commonly experience a deterioration in glycaemic control in the early post-transplant period, due to the effects of prednisolone on gluconeogenesis, CNI-related pancreatic beta cell toxicity and enhanced renal clearance of insulin. Elevated glucose profiles have been associated with poorer graft outcomes. The glucokinase activator AZD1656 has been shown to be a potent anti-diabetic medication and safe in patients with T2DM, including those with chronic kidney disease. Recent data has shown that glucokinase activation increases regulatory T cell(Treg) migration and trafficking. We propose to study the safety and efficacy of AZD1656 in optimising glycaemic control and stimulating Treg migration to the transplant in a population of renal transplant patients with pre-existing T2DM. Ethical approval has been obtained from the relevant regulatory bodies.
Methods
ADOPTION is a single site, placebo-controlled, double-blind randomised clinical trial of AZD1656 in patients with T2DM and a new renal transplant. Eligible, consented patients at a tertiary centre are randomised to a 3-month course of either AZD1656 or placebo within 24 hours of transplantation. Clinical and laboratory data is collected and assessed at baseline and throughout their participation in the study. The primary endpoint is the mean change in peripheral Tregs between baseline and 3 months as analysed by flow cytometry. Secondary endpoints include graft outcomes, histological staining for Tregs, glycaemic control and safety endpoints. Patients are closely monitored for the first 14 weeks post-transplant. Their records are reviewed at 1 year.
Results
We plan to recruit 50 patients. There are no interim analyses planned.
Conclusion
AZD1656 offers the chance to achieve better glycaemic control in the early post transplant period, but of greater potential benefit is the immunomodulatory effect which could lead to improved renal outcomes. We hope to demonstrate that AZD1656 increases Treg localisation to the renal transplant and provides an effective and safe adjunct for the management of diabetes in the early post-transplant period. A positive signal generated by this pilot study would provide future opportunities for further study and we look forward to sharing our results with the ASN in the near future.
Funding
- Commercial Support – AstraZeneca