AZD1656 in Transplantation With Diabetes tO PromoTe Immune TOleraNce
- Conditions
- Renal TransplantKidney Transplant; ComplicationsEnd Stage Renal DiseaseType 2 DiabetesDiabetes Mellitus, Type 2
- Interventions
- Drug: Placebo
- Registration Number
- NCT05216172
- Lead Sponsor
- Queen Mary University of London
- Brief Summary
AZD1656 in Transplantation with Diabetes tO PromoTe Immune TOleraNce: a single site, placebo-controlled, double-blind randomised clinical trial of AZD1656 in renal transplant patients with Type 2 diabetes
- Detailed Description
Transplant recipients with pre-existing Type 2 diabetes frequently experience a deterioration in glycaemic control in the early post-transplant period, largely due to the significant immunosuppression burden at this stage. 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. The investigators propose to study the safety and efficacy of AZD1656 in optimising the glycaemic control and in stimulating Treg migration to the transplant kidney in a population of renal transplant patients with pre-existing T2DM.
ADOPTION is a single site, placebo-controlled, double-blind randomised clinical trial of AZD1656 in patients with Type 2 diabetes who have received a new renal transplant. Eligible, consented patients are randomised to a 3 month course of either active drug or placebo within 24 hours of transplantation. Clinical and laboratory data will be collected and assessed at baseline and throughout their participation in the study. The study plans to enrol 50 patients. There are no interim analyses planned. The primary endpoint will be the mean change in peripheral Tregs between baseline and 3 months as analysed by flow cytometry.
Ethical approval was obtained from the East of England - Cambridge East Ethics Committee (REC 19/EE/0209) prior to commencing the study. All study-related data will be used by the Sponsor in accordance with local data protection law. Results of the trial will be submitted for publication in a peer-reviewed journal.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 26
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Females or males aged 18 years and above
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Having undergone renal transplantation at the Royal London Hospital within the previous 24 hours
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A pre-transplant diagnosis of Type 2 diabetes
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Provision of written, informed consent prior to any study specific procedures
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In women of childbearing potential* documentation of a negative pregnancy test during admission for renal transplant.
- Women of childbearing potential are defined as women following menarche until becoming post-menopausal, unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A post-menopausal state is defined as the absence of menses for 12 months without an alternative medical cause.
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Unable to consent
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Known allergy/intolerance to AZD1656
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Pregnant or breastfeeding women
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Planning on becoming pregnant/unwilling to use highly effective contraception* during the 3 month treatment period and for 2 weeks afterwards (i) In the case of men with sexual partners who are women of childbearing potential: refusal to wear a condom and female partner planning on becoming pregnant/unwilling to use highly effective contraception* during the 3 month treatment period and for 2 weeks afterwards
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Clinically significant history of abnormal physical and/or mental health as judged by the investigator other than conditions related to chronic kidney disease
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Current or planned use of strong inhibitors of CYP2C8
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Participation in an investigational drug trial in the 3 months prior to administration of the initial dose of study drug
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Highly effective contraception methods are defined as those that can achieve a failure rate of <1% per year when used correctly and consistently. These include:
- Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation - either oral, transvaginal or transdermal
- Progestogen-only hormonal contraception associated with inhibition of ovulation - either oral, injectable or implantable
- Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)
- Bilateral tubal occlusion
- Vasectomised partner - provided that the partner is the sole sexual partner of the participant and that the vasectomised partner has received medical assessment of surgical success
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AZD1656 AZD1656 AZD1656 100mg BD for 3 months placebo Placebo placebo 100mg BD for 3 months
- Primary Outcome Measures
Name Time Method peripheral regulatory T cells 14 weeks Change in mean peripheral Treg cell number between baseline and 3 months measured using flow cytometry analysis (FACS) in AZD1656 and placebo arms
- Secondary Outcome Measures
Name Time Method delayed graft function 1 week Incidence of delayed graft function, defined as the need for dialysis within 1 week post-transplant
kidney transplant rejection 3 months Episodes of acute rejection (defined as biopsy proven acute rejection)
regulatory T cells in renal transplant 3 months Histological staining for Treg cells in renal biopsy tissue between baseline and 3 month protocol biopsy
incidence of treatment emergent adverse events 3 months safety endpoints including hypoglycaemic episodes
kidney transplant function 3 months Graft function: (eGFR) at month 3
glycemic control: HbA1c 3 months Diabetic control between baseline and month 3 using change in HbA1c measurement
number of participants with increase or decrease in concurrent anti-diabetic medication 3 months Dose of other anti-diabetic medication between baseline and month 3 (descriptive)
change in HOMA-IR measurement between baseline and month 3 3 months Insulin resistance: HOMA IR measurement at month 3
incidence of treatment emergent adverse events (with particular reference to episodes of infection) 3 months Episodes of opportunistic infections: bacterial and viral (descriptive)
Trial Locations
- Locations (1)
Royal London Hospital Barts Health NHS Trust
🇬🇧London, United Kingdom