Semaglutide for the Prevention Of Post-Transplant Diabetes Mellitus
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 37
- 试验地点
- 4
- 主要终点
- 2-hour OGTT
研究概览
简要总结
The study aims to determine the short-term efficacy, mechanisms and safety of 24 weeks of semaglutide therapy in 37 KTR at risk of post-transplant diabetes mellitus (PTDM).
详细描述
A kidney transplant is the best treatment for people living with kidney failure as it allows people to live longer with a better quality of life. However, one in four kidney transplant recipients will develop diabetes after transplant. This is largely due to the medications that must be used to prevent rejection of the transplant. Kidney transplant recipients who get diabetes after transplant are up to three times more likely to have heart disease and die prematurely. To date, there are no treatments to prevent the development of diabetes after kidney transplant. Semaglutide is a drug that is commonly used to treat diabetes and obesity. The investigators believe that semaglutide is a safe and effective drug which can prevent the development of diabetes in kidney transplant recipients. Therefore, the investigators are conducting a study where kidney transplant recipients who are at increased risk of developing diabetes after transplant will receive semaglutide for 24 weeks after their transplant. The study will determine whether semaglutide is effective in decreasing blood sugar levels and the rate of diabetes. The investigators will also study other important markers of health including body weight and cholesterol levels as well as liver, kidney and heart function. Diabetes after transplant is a common problem, and preventing it is extremely important to allowing kidney transplant recipients to live longer and better lives. The results of this study will allow the investigators to determine if semaglutide is a safe and effective option for the prevention of diabetes in kidney transplant recipients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Signed and dated written informed consent.
- •Adult (≥18 years) recipients of a living or deceased donor kidney transplant
- •Between 4- and 12-weeks post kidney transplant
- •Stable kidney function defined as an eGFR > 30 ml/min/1.73m2 (CKD-EPI)
- •At risk for PTDM at the time of transplant based on the following criteria:
- •BMI ≥ 25 kg/m2, or
- •Fasting plasma glucose 6.1-6.9 mmol/L (impaired fasting glucose), or
- •2hr OGTT plasma glucose 7.8-11.0 (impaired glucose tolerance), or
- •HbA1C 5.5-6.4% (at risk for DM or prediabetes).
排除标准
- •Established diagnosis of type 1 or type 2 DM as per Diabetes Canada (including the need for glucose-lowering therapy for hyperglycemia at the time of screening)
- •Kidney-Pancreas transplant recipient
- •Acute coronary syndrome, transient ischemic attack or stroke within 30 days prior to screening
- •History of pancreatitis
- •Personal or family history of medullary thyroid cancer or MEN2B
- •Women who are pregnant, nursing or plan on becoming pregnant whilst in the trial
- •Use of GLP1RA in the 30 days prior to screening
- •Contraindication to MRI (applicable only to those undergoing the optional MRI assessments)
- •With known or suspected hypersensitivity to semaglutide or related products
- •Patient not able to understand and comply with study requirements, based on Investigator's judgment.
- •Any other clinical condition that, based on Investigator's judgement, would jeopardize patient safety during trial participation or would affect the study outcom
- •History of glucose-galactose malabsorption syndrome
研究组 & 干预措施
Semaglutide
Patients will be up-titrated as tolerated starting at 0.25 mg subcutaneous semaglutide once weekly for 4 weeks, followed by 0.5 mg, 1.0 mg, and 1.7 mg semaglutide for 4 weeks each, and then 2.4 mg subcutaneous semaglutide once weekly for 8 weeks. Semaglutide can be down-titrated by the investigator to lower doses or up-titrated at slower rates if not tolerated by the participant.
干预措施: Semaglutide 0.25 mg (Drug)
Semaglutide
Patients will be up-titrated as tolerated starting at 0.25 mg subcutaneous semaglutide once weekly for 4 weeks, followed by 0.5 mg, 1.0 mg, and 1.7 mg semaglutide for 4 weeks each, and then 2.4 mg subcutaneous semaglutide once weekly for 8 weeks. Semaglutide can be down-titrated by the investigator to lower doses or up-titrated at slower rates if not tolerated by the participant.
干预措施: Semaglutide 1.7mg subcutaneous (Drug)
Semaglutide
Patients will be up-titrated as tolerated starting at 0.25 mg subcutaneous semaglutide once weekly for 4 weeks, followed by 0.5 mg, 1.0 mg, and 1.7 mg semaglutide for 4 weeks each, and then 2.4 mg subcutaneous semaglutide once weekly for 8 weeks. Semaglutide can be down-titrated by the investigator to lower doses or up-titrated at slower rates if not tolerated by the participant.
干预措施: Semaglutide 2.4 MG/0.75 ML Subcutaneous Solution [WEGOVY] (Drug)
Semaglutide
Patients will be up-titrated as tolerated starting at 0.25 mg subcutaneous semaglutide once weekly for 4 weeks, followed by 0.5 mg, 1.0 mg, and 1.7 mg semaglutide for 4 weeks each, and then 2.4 mg subcutaneous semaglutide once weekly for 8 weeks. Semaglutide can be down-titrated by the investigator to lower doses or up-titrated at slower rates if not tolerated by the participant.
干预措施: Semaglutide 1.0 mg (Drug)
Semaglutide
Patients will be up-titrated as tolerated starting at 0.25 mg subcutaneous semaglutide once weekly for 4 weeks, followed by 0.5 mg, 1.0 mg, and 1.7 mg semaglutide for 4 weeks each, and then 2.4 mg subcutaneous semaglutide once weekly for 8 weeks. Semaglutide can be down-titrated by the investigator to lower doses or up-titrated at slower rates if not tolerated by the participant.
干预措施: Semaglutide 0.5 mg (Drug)
结局指标
主要结局
2-hour OGTT
时间窗: 24 weeks
The primary outcome of this study is the change in plasma glucose at 120 minutes following a 75g oral glucose challenge (2-hour OGTT) at 24 weeks. The 2-hour OGTT was selected as the primarily outcome in this study for the following reasons: 1) In selecting a surrogate outcome for PTDM in KTR, there are limitations to HbA1c and fasting glucose in this population; 2) The 2-hour OGTT is the recommended test for the diagnosis of PTDM in KTR and 3) The use of OGTT has been used in other PTDM prevention studies.
次要结局
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability](24 weeks)
- Estimated GFR(24 weeks)
- Change in fasting blood glucose(24 weeks)
- GFR(24 weeks)
- Urinary glucose excretion(24 weeks)
- Change in serum insulin(24 weeks)
- Change in HbA1c(24 weeks)
- Albuminuria(24 weeks)
- Natriuresis(24 weeks)
- Percentage of body fat(24 weeks)
- Change in fasting lipid profile(24 weeks)
- Change in liver enzymes(24 weeks)
- Change in fibrosis level(24 weeks)
- Change in steatosis level(24 weeks)
- Change in waist circumference(24 weeks)
- Change in body weight(24 weeks)
- Systolic blood pressure(24 weeks)
- Diastolic blood pressure(24 weeks)
- Mean arterial pressure(24 weeks)
- Percentage of extracellular fluid(24 weeks)
研究者
Sunita Singh, MD, MSc, FRCPC
Principal Investigator
University Health Network, Toronto