renal transplant AND type 2 diabetes MedDRA version: 20.0 Level: LLT Classification code 10023438 Term: Kidney transplant System Organ Class: 100000004865 MedDRA version: 20.0 Level: PT Classification code 10012601 Term: Diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Name: AZD1656
Product Code: AZD1656
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Sponsors
Queen Mary University London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: a) Females or males aged 18 years and above b) Having undergone renal transplantation at the Royal London Hospital within the previous 24 hours c) A pre-transplant diagnosis of Type 2 diabetes d) Provision of written, informed consent prior to any study specific procedures e) 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. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: a) Unable to consent b) Known allergy/intolerance to AZD1656 c) Pregnant or breastfeeding women d) Planning on becoming pregnant/unwilling to use highly effective contraception* during the 3 month treatment period and for 2 weeks afterwards a. 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 e) Clinically significant history of abnormal physical and/or mental health as judged by the investigator other than conditions related to chronic kidney disease f) Current or planned use of strong inhibitors of CYP2C8 g) Participation in an investigational drug trial in the 3 months prior to administration of the initial dose of study drug *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 • Sexual abstinence – refrain from heterosexual intercourse for the duration of period defined to be at risk
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Will treating post-transplant patients with glucokinase activator (AZD1656) compared to placebo for 3 months improve the function of their transplant kidney via a change in the levels of immune cells (regulatory T cells)? We will measure this by measuring the number of regulatory T cells in blood samples taken from the patients.;Secondary Objective: We will also be assessing whether the regulatory T cells leave the circulation and migrate to the transplant kidney by looking for them with a histological stain in the two biopsies which are routinely taken as part of standard of care: at time of implantation and at 3 months. We will be assessing the transplant function by monitoring the incidence of delayed graft function (defined as the need for dialysis within the first week post-transplant) and by measuring eGFR (a measure of kidney function) at 3 months. As glucokinase activators have also been shown to have a (transient) effect on lowering blood sugars, we will be investigating the effect of AZD1656 on the glycaemic control of participants by assessing: a) HbA1c monitoring between baseline and 3 months b) the dose of any other anti-diabetic medication required between baseline and 3 months c) insulin resistance by performing a homeostatic measurement at 3 months d) the number of any hypoglycaemic episodes We will also monit;Primary end point(s): The primary end point is the change in mean peripheral Treg cell number between baseline and 3 months post-transplant as measured using flow cytometry analysis (FACS) between patients receiving AZD1656 and placebo. This will be analysed during the first data analysis (see below). ;Timepoint(s) of evaluation of this end point: Time point of primary end point is at 3 months post-transplant. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Histological staining for T-reg cells in renal biopsy tissue between baseline and 3 month protocol biopsy 2) Incidence of delayed graft function, defined as the need for dialysis within 1 week post-transplant 3) Diabetic control between baseline and month 3 using change in HbA1c measurement 4) Dose of other antidiabetic medication between baseline and month 3 (descriptive) 5) Safety endpoints: i.e. number of hypoglycaemic episodes (descriptive) 6) Insulin resistance: HOMA IR measurement at month 3 7) Graft function: (eGFR) at month 3 8) Episodes of acute rejection (defined as biopsy proven acute rejection) 9) Episodes of opportunistic infections: bacterial and viral (descriptive) 10) 12-month graft function (eGFR) and diabetic control (HbA1c) to assess legacy effect 11) Differences in other peripheral T cell populations, measured by FACS analysis ;Timepoint(s) of evaluation of this end point: Secondary end-point assessment will take place during study visits at recruitment, and weeks 1, 2, 4, 8, 12 and 14 post-transplant. There will be a further assessment at 1 year post-transplant (9 months post-completion of study drug). | — |
Countries
United Kingdom
Contacts
Public ContactDr Kieran McCafferty
Diabetic Kidney Disease Centre
Outcome results
None listed