A Two Arm, Open Label, Pilot Study to Evaluate the Safety and Efficacy of the Combined Use of Once Daily 10mg Dapagliflozin and Once Weekly 1.0mg Semaglutide in Kidney Transplant Recipients
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Proximal tubular natriuresis with combination therapy
研究概览
简要总结
The study aims to determine the short-term efficacy, mechanisms and safety of 12 weeks of dapagliflozin and semaglutide combination therapy in 20 KTR, with and without T2D.
详细描述
Kidney transplantation improves survival and quality of life for patients with kidney failure. However, treatment options to protect the heart and the kidney in transplant recipients are lacking. Sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RA) are novel anti-diabetic drugs which not only lower blood sugar, but also lower blood pressure in the kidney's individual filtering units and protect kidney function in the long term. It is unclear if the protective mechanisms of these drugs also occur in people with a kidney transplant. Several smaller studies have shown that SGLT2 inhibitors or GLP-1RA used alone are safe in people with kidney transplants. No studies have yet to look at the combined use of SGLT2 inhibitors and GLP-1RA in kidney transplant recipients (KTR).
The purpose of the HALLMARK study is to determine the mechanisms and safety of the combination use of semaglutide, a GLP-1RA, and dapagliflozin, a SGLT2 inhibitor. To investigate this, 20 kidney transplant recipients with and without diabetes will be treated with both semaglutide or dapagliflozin for 12 weeks followed by a combination of semaglutide and dapagliflozin for 12 weeks. The study will measure salt and water removal as well as the effect on blood pressure, kidney function, heart function, liver stiffness as well as the safety of these agents.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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.
- •Patients aged ≥18 years with KTR
- •>3 months post kidney transplantation
- •Estimated glomerular filtration rate [eGFR] ≥20 ml/min/1.73m2
- •BP <160/100 and >90/60 at screening
- •Body-mass index [BMI] between 18.5-40kg/m2
- •In patients with T2D or PTDM, HbA1c <12.0%;
排除标准
- •Type 1 diabetes.
- •History of multi-organ transplant
- •Acute coronary syndrome, transient ischemic attack or stroke within 30 days prior to screening
- •Impending need for kidney biopsy or rapid decline in eGFR within 30 days prior to screening
- •Actively treated BK, CMV or EBV infection
- •Recurrent pyelonephritis or need for indwelling or self-catheterization
- •Prior amputation or ischemic rest pain
- •Women who are pregnant, nursing, or who plan to become pregnant whilst in the trial.
- •History of pancreatitis
- •Personal or family history or medullary thyroid cancer or MEN2B
- •History of unstable diabetic retinopathy within 1 year prior to screening
- •Use of SGLT2i or GLP-1RA within 30 days prior to screening.
- •Current and frequent episodes of hypoglycemia
- •Current history of DKA requiring medical intervention or hospitalization
- •With current risk of volume depletion, hypotension and/or electrolyte imbalance
- •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 outcome (e.g. immunocompromised patients, active malignancy, patients who might be at higher risk of developing genital or mycotic infections, patients with chronic viral infections, uncontrolled hypertension, cardiorenal and/or hepatorenal syndrome etc.).
研究组 & 干预措施
Dapagliflozin
Dapagliflozin Tablets Total Dose 10mg daily for 12 weeks
干预措施: Semaglutide, 1.0 mg/mL (Drug)
Semaglutide
Semaglutide Subcutaneous 0.25mg once weekly for 4 weeks, then 0.5mg once weekly for 4 weeks, then 1mg once weekly for 4 weeks.
干预措施: Semaglutide, 1.0 mg/mL (Drug)
Dapagliflozin
Dapagliflozin Tablets Total Dose 10mg daily for 12 weeks
干预措施: Dapagliflozin 10 MG (Drug)
Semaglutide
Semaglutide Subcutaneous 0.25mg once weekly for 4 weeks, then 0.5mg once weekly for 4 weeks, then 1mg once weekly for 4 weeks.
干预措施: Dapagliflozin 10 MG (Drug)
结局指标
主要结局
Proximal tubular natriuresis with combination therapy
时间窗: From baseline to combination therapy end (24 weeks)
Measured by fractional excretion of sodium
Proximal tubular natriuresis with monotherapy
时间窗: From baseline to monotherapy end (12 weeks)
Measured by fractional excretion of sodium
次要结局
- Liver stiffness(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Safety: the incidence of hypotension(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Change in percentage of glycated hemoglobin (HbA1c)(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Change in concentration of urine glucose excretion(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Safety: The incidence of urinary and mycotic infections.(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Safety: the incidence of acute kidney injury.(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Safety: The incidence of amputations.(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Safety: The number of allergic reaction events.(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Measured Glomerular Filtration Rate(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Estimated Glomerular Filtration Rate(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Urinary 8-hydroxydeoxyguanosine and 8-isoprostane concentration(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Urinary albumin excretion(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Arterial stiffness(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Diastolic function(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Change in body composition (percent body mass, body fat, and muscle mass)(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Change in body weight(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Safety: The incidence of hyperkalemia(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Safety: The incidence of pancreatitis or biliary complications(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
- Safety: The number of ketoacidosis events.(From baseline to monotherapy end (12 weeks) and combination therapy end (24 weeks) ])
研究者
Sunita Singh, MD, MSc, FRCPC
Clinician Scientist
University Health Network, Toronto