A RAndomized trIal Examining the Effect of Subcutaneous Semaglutide on Kidney Transplant Candidacy for Patients With Stage 4-5 CKD or Dialysis-dependent ESKD
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- Kidney Transplant Eligibility
研究概览
简要总结
This randomized study evaluates the effect of subcutaneous semaglutide /in combination with lifestyle counseling in patients with type 2 diabetes mellitus (T2DM), overweight/obesity, and stage 4-5 chronic kidney disease (CKD) or dialysis-dependent end-stage kidney disease (ESKD) on patients' eligibility for kidney transplantation at the end of 9 months.
详细描述
Transplant policies regarding listing consider uncontrolled diabetes and severe obesity to be contraindications though there is great variability for exact BMI (35-45 kg/m2) and A1c (9-10%) thresholds for listing by center. Glucagon-lowering peptide-1 receptor agonists (GLP-1 RAs) offer great promise in this population as they have been shown to reduce weight, central adiposity, A1c, and risk of cardiovascular outcomes with similar effects in patients with and without CKD.
In this double-blind, placebo-controlled randomized controlled trial, the investigators will evaluate the effect of subcutaneous semaglutide 1.34 mg/ml (up to 1.0 mg per week) in combination with lifestyle counseling in patients with T2DM, overweight/obesity, and stage 4-5 CKD or dialysis-dependent ESKD on patients' eligibility for kidney transplantation in terms of diabetes control (A1c <9%) and obesity (BMI <35 kg/m2 or 35-40 kg/m2 with waist circumference <120 cm) at the end of 9 months.
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 placebo-controlled double-blind clinical trial. Study investigators and participants will be blinded to treatment allocation.
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
- •Age ≥ 18 years
- •BMI 25-45 kg/m2
- •Advanced CKD* (last eGFR <30 ml/min/1.73m2 in EHR or ESKD on dialysis prior to screening) or stage G3B/A2-3 CKD (eGFR 30 to <45 ml/min/1.73m2 with albumin/creatinine ratio >30 mg/g).
- •Fulfill kidney transplant listing criteria except for one or more of the following reasons (1: uncontrolled diabetes [A1c ≥9%); 2: severe obesity (BMI ≥ 40 kg/m2 or BMI 35-40 kg/m2 with waist circumference >120 cm). See exclusion criteria for general contraindications used for transplant listing used by majority of U.S. transplant centers].
- •Ability to provide informed consent before any trial-related activities
- •Access to a telephone
- •The cause of the CKD does not need to be due specifically to diabetes
- •Exclusion Criteria (General contraindications used for transplant listing used by majority of U.S. transplant centers)
- •Active malignancy
- •History of pancreatitis
- •Active substance abuse
- •Severe COPD
- •Pulmonary fibrosis
- •Symptomatic angina or recent myocardial infarction within 6 months
- •Severe peripheral vascular disease
- •Cirrhosis
- •New York Health Association (NYHA) Class III-IV congestive heart failure
- •Severe cognitive impairment
- •Drug addiction
- •History of non-adherence to therapy
- •Active infection
- •Expected life expectancy < 5 years
- •Additional exclusion criteria
- •Type 1 diabetes mellitus
- •History of diabetic ketoacidosis within the last 12 months
- •Planning on undergoing bariatric surgery in next 9 months.
- •Pregnant, breast-feeding, or planned pregnancy prior to the end of participation or not using adequate contraceptive measures
- •Self-reported average consumption of > 21 alcoholic beverages per week or binge drinking
- •Psychiatric hospitalization in past year
- •Principal investigator discretion (i.e. concerns about safety, compliance)
- •Known or suspected allergy to trial medication
- •Previous participation (i.e. randomized) in this trial
- •Use of GLP1-RA or pramlintide within 90 days prior to screening
- •Use of metformin (contraindicated with eGFR < 30 ml/min/1.73m2)
- •Use of DPP-4 inhibitors within 30 days prior to screening
- •Personal or family history of medullary thyroid cancer, multiple endocrine neoplasia types 2A and 2B syndrome
- •Last hemoglobin A1c ≥ 12% or A1c <6% (to avoid risk of hypoglycemia) prior to screening
排除标准
- 未提供
研究组 & 干预措施
Semaglutide
This arm will receive semaglutide.
干预措施: Semaglutide 2 mg/1.5 ml (1.34 mg/ml), prefilled pen-injector for subcutaneous injection solution (Drug)
Placebo
This arm will receive placebo.
干预措施: Placebo 1.5 ml, prefilled pen-injector for subcutaneous injection solution (Drug)
结局指标
主要结局
Kidney Transplant Eligibility
时间窗: Ascertained at the end of 9 months
Proportion either listed for kidney transplant at 9 months or meeting the following kidney transplant candidacy criteria for A1c (\<9%) and obesity (BMI \<35 kg/m2 or BMI 35-40 kg/m2 with waist circumference \<120 cm)
次要结局
- Change in Hemoglobin A1c (HgbA1c)(From baseline to 9 months)
- Change in BMI(From baseline to 9 months)
- Change in Waist Circumference(From baseline to 9 months)
- Change in Waist-to-hip Ratio(From baseline to 9 months)
- Change in Body Fat Percentage(From baseline to 9 months)
- New Activation on the Transplant List(Assessed at end of 9 months)
- Receipt of Kidney Transplant(Assessed at end of 9 months)
研究者
Alexander Chang
Assistant Professor, Clinical Research
Geisinger Clinic