AZD1656 in Transplantation With Diabetes tO PromoTe Immune TOleraNce
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- peripheral regulatory T cells
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This is a double blind placebo study: both the patient and the study team will be blinded to the treatment intervention.
Pharmacy staff who dispense the study medication will not be blinded, nor will Sponsor Office staff responsible for reporting unblinded SUSAR reports to the MHRA.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Females or males aged 18 years and above
- •Having undergone renal transplantation at the Royal London Hospital within the previous 24 hours
- •A pre-transplant diagnosis of Type 2 diabetes
- •Provision of written, informed consent prior to any study specific procedures
- •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.
排除标准
- •Unable to consent
- •Known allergy/intolerance to AZD1656
- •Pregnant or breastfeeding women
- •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
- •Clinically significant history of abnormal physical and/or mental health as judged by the investigator other than conditions related to chronic kidney disease
- •Current or planned use of strong inhibitors of CYP2C8
- •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
研究组 & 干预措施
AZD1656
AZD1656 100mg BD for 3 months
干预措施: AZD1656 (Drug)
placebo
placebo 100mg BD for 3 months
干预措施: Placebo (Drug)
结局指标
主要结局
peripheral regulatory T cells
时间窗: 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
次要结局
- delayed graft function(1 week)
- kidney transplant rejection(3 months)
- regulatory T cells in renal transplant(3 months)
- incidence of treatment emergent adverse events(3 months)
- kidney transplant function(3 months)
- glycemic control: HbA1c(3 months)
- number of participants with increase or decrease in concurrent anti-diabetic medication(3 months)
- change in HOMA-IR measurement between baseline and month 3(3 months)
- incidence of treatment emergent adverse events (with particular reference to episodes of infection)(3 months)