Open, Randomized, Unicenter Study Comparing Metabolic Surgery With Intensive Medical Therapy to Treat Diabetic Kidney Disease
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Mean differenceGlomerular filtration rate (GFR)
研究概览
简要总结
Proven therapy for DKD is primarily limited to RAAS blockers and SLGT2i. Weight reduction has the potential to become an additional and much needed treatment option. Of all the weight reduction strategies metabolic surgery is suited to be the most effective. Yet no study has of yet compared the effect of metabolic surgery against best medical treatment on the progression of DKD. This pilot trial is designed to be the first determine the efficacy of metabolic surgery in slowing progression of DKD as compared to best medical therapy. The study design will address all the major limitations previously documented, including the major dilemma of estimating versus measuring GFR. Of note, the study's design will allow its sample size to be adjusted upward using an adaptive design if necessary, to achieve statistical significance. It will also inform study design and sample size issues for all future studies in this field. The payoff of establishing metabolic surgery as a new and effective intervention to slow progression to ESRD would be great in terms of reducing patient suffering and societal costs.
This will be an open-label, randomized trial involving sixty (60) patients with diabetic kidney disease (DKD) and obesity who will undergo Roux-en-Y gastric bypass (RYGB) in the intervention arm or receive best medical treatment (BMT) in the control arm.
The aim of this prospective, open, randomized study is to evaluate the efficacy and safety of RYGB surgery versus best medical treatment on the progression of DKD in patients with type 2 diabetes and obesity.
详细描述
This will be an open-label, randomized trial involving sixty (60) patients with DKD and obesity who will undergo RYGB (intervention arm) or receive BMT (control arm).
Thirty (30) obese patients with DKD will undergo gastric bypass. Patients will also receive standard of care medical therapy for DKD (ACEI or ARB + SGLT2i) and T2DM (metformin, glitazones, incretin therapy - DPP4 inhibitor and GLP-1 analogs - and insulin, if necessary). Other comorbidities, such as hypertension and dyslipidemia, will be treated according to the latest recommendations of the ADA. The surgical procedure will consist of a laparoscopic surgery performed by an experienced surgeon (approximately 6000 bariatric surgeries), who is accredited as surgeon of excellence by the Brazilian Society of Bariatric and Metabolic Surgery and Surgical Review and Surgical Review Corporation program since 2009.
Thirty (30) obese patients with DKD will undergo best medical treatment for DKD (ACEI or ARB + SGLT2i) and T2DM (metformin, glitazones, incretin therapy - DPP4 inhibitor and GLP-1 analogs - and insulin, if necessary). Other comorbidities, such as hypertension and dyslipidemia, will be treated according to the latest recommendations of the ADA.
Regarding medication therapy: Metformin will be maintained in the postoperative period while fasting glycemia is above 100 mg/dL unless contraindicated. Anti-antihypertensive drugs and medications for dyslipidemia will be maintained in the postoperative period, unless contraindicated. Micronutrient supplementation (vitamins and mineral salts) will be prescribed to all patients undergoing metabolic surgery. Patients allocated to the control group will receive the same supplementation if necessary.
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
- None
入排标准
- 年龄范围
- 30 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Female or male aged ≥30 and ≤70 years
- •Diabetic kidney disease as defined by an estimated glomerular filtration rate (eGFR) (as estimated by CKD-EPI creatinine + cystatin C equation)72 between 45-59l/min/1.73m2 and macroalbuminuria (≥ 300 mg/g) in a 24 hr urine sample
- •BMI ≥30-40 kg/m2
- •Fasting C-peptide over 1 ng/ml
- •Negative glutamic acid decarboxylase autoantibodies test
- •Patients having received accurate information about the surgery and requesting the procedure
- •Patients having understood and accepted the need for long-term medical and surgical follow-up
- •Effective method of contraception in women of child-bearing age
- •Signed informed consent document
排除标准
- •Refusal to participate
- •Autoimmune diabetes/type 1 diabetes
- •Previous abdominal operations that would complicate a metabolic surgery or increase surgical risk
- •Previous malabsorptive and restrictive surgeries
- •Malabsorptive syndromes and inflammatory bowel disease
- •Significant and/or severe hepatic disease that may complicate metabolic surgery
- •Pregnancy or women of childbearing age without effective contraceptive
- •Recent history of neoplasia (< 5 years), except for non-melanoma skin neoplasms
- •History of liver cirrhosis, active chronic hepatitis, active hepatitis B or hepatitis C
- •Major cardiovascular event in the last 6 months
- •Current angina
- •Pulmonary embolism or severe thrombophlebitis in the last 2 years
- •Positive HIV serum testing
- •Mental incapacity or severe mental illness
- •Severe psychiatric disorders that would complicate follow-up after randomization
- •Alcoholism or illicit drug use
- •Uncontrolled coagulopathy
- •Participation in other clinical trials in the past 30 days
- •Inability to tolerate RAAS blockers and/or SGLT2i
- •Iodine allergy
- •History of acute kidney injury requiring renal replacement therapy
- •Dialysis dependency
- •Kidney transplantation
- •Use of immunosuppressive drugs, chemotherapy and/or radiotherapy
- •Any disorder which, in the opinion of the investigator, might jeopardize subject's safety or compliance with the protocol
研究组 & 干预措施
RYGB (intervention arm)
Thirty (30) obese patients with DKD will undergo gastric bypass. Patients will also receive standard of care medical therapy for DKD (ACEI or ARB + SGLT2i) and T2DM (metformin, glitazones, incretin therapy - DPP4 inhibitor and GLP-1 analogs - and insulin, if necessary). Other comorbidities, such as hypertension and dyslipidemia, will be treated according to the latest recommendations of the ADA. The surgical procedure will consist of a laparoscopic surgery performed by an experienced surgeon (approximately 6000 bariatric surgeries), who is accredited as surgeon of excellence by the Brazilian Society of Bariatric and Metabolic Surgery and Surgical Review and Surgical Review Corporation program since 2009.
干预措施: Roux-en-Y gastric bypass (Procedure)
RYGB (intervention arm)
Thirty (30) obese patients with DKD will undergo gastric bypass. Patients will also receive standard of care medical therapy for DKD (ACEI or ARB + SGLT2i) and T2DM (metformin, glitazones, incretin therapy - DPP4 inhibitor and GLP-1 analogs - and insulin, if necessary). Other comorbidities, such as hypertension and dyslipidemia, will be treated according to the latest recommendations of the ADA. The surgical procedure will consist of a laparoscopic surgery performed by an experienced surgeon (approximately 6000 bariatric surgeries), who is accredited as surgeon of excellence by the Brazilian Society of Bariatric and Metabolic Surgery and Surgical Review and Surgical Review Corporation program since 2009.
干预措施: Best medical treatment (Drug)
BMT (control arm).
Thirty (30) obese patients with DKD will undergo best medical treatment for DKD (ACEI or ARB + SGLT2i) and T2DM (metformin, glitazones, incretin therapy - DPP4 inhibitor and GLP-1 analogs - and insulin, if necessary). Other comorbidities, such as hypertension and dyslipidemia, will be treated according to the latest recommendations of the ADA.
干预措施: Best medical treatment (Drug)
结局指标
主要结局
Mean differenceGlomerular filtration rate (GFR)
时间窗: At 12 and 36 months after randomization
Mean difference in GFR between BMT and RYGB at the pre-specified time points of 12 and 36 months after randomization
次要结局
- Hypoglycemic adverse events(From baseline to 12 and 36 months)
- Change in twenty-four hour urinary albumin/protein excretion(From baseline to 12 and 36 months)
- Change in CKD stage and CKD prognostic risk(From baseline to 12 and 36 months)
- Change in GFR, eGFR and 24 hr creatinine clearance(From baseline to 12 and 36 months)
- Change in ventricular mass(From baseline to 12 and 36 months)
- Proportion of participants with ≥30%, ≥40%, and ≥50% reduction in GFR measurements(From baseline to 12 and 36 months)
- Decline in eGFR, sustained low eGFR, kidney transplantation, maintenance dialysis, and kidney death(Time to occurrence (from baseline))
- Change in body weight(From baseline to 12 and 36 months)
- Change in waist circumference(From baseline to 12 and 36 months)
- Change in fasting glucose(From baseline to 12 and 36 months)
- Change in HbA1c(From baseline to 12 and 36 months)
- Change in blood pressure(From baseline to 12 and 36 months)
- Changes in serum calcium and phosphorus,(From baseline to 12 and 36 months)
- Improvements in micro- or macroalbuminuria(From baseline to 12 and 36 months)
- Maintenance dialysis, kidney transplantation, kidney death, and GFR < 15 ml/min(At 12 and 36 months after randomization)
- Change in body mass index(From baseline to 12 and 36 months)
- Medications to maintain optimal diabetes and blood pressure control(From baseline to 12 and 36 months)
- Changes in total cholesterol, triglycerides, LDL and HDL levels(From baseline to 12 and 36 months)
- Number of participants achieving LDL < 100 mg/dL and HDL > 40mg/dL(From baseline to 12 and 36 months)
- Change in mineral bone density(From baseline to 12 and 36 months)
- Change in quality of life(From baseline to 12 and 36 months)
- Change in basal insulin(From baseline to 12 and 36 months)
- Days hospitalized(From baseline to 12 and 36 months)
- Change in homeostasis model assessment (HOMA) scores(From baseline to 12 and 36 months)
- Remission in type 2 diabetes(At 12 and 36 months after randomization)
- High sensitivity c-reactive protein(From baseline to 12 and 36 months)
- Kidney volumes(From baseline to 12 and 36 months)
- Change in parathyroid hormone (PTH)(From baseline to 12 and 36 months)
- Adverse events(From baseline to 12 and 36 months)
- Mortality(From baseline to 12 and 36 months)
- Change in calcium and oxalate excretion(From baseline to 12 and 36 months)
- Acute kidney injury(From baseline to 12 and 36 months)
- Adverse cardiovascular events (nonfatal stroke, nonfatal MI, cardiovascular death)(From baseline to 12 and 36 months)
- Change in urinary volume(From baseline to 12 and 36 months)
- Change in muscle strength(From baseline to 12 and 36 months)
- Change in ejection fraction(From baseline to 12 and 36 months)
- Costs of care and health care utilization(From baseline to 12 and 36 months)
研究者
Ricardo Vitor Cohen, MD
Ricardo Vitor Cohen, MD, PhD
Hospital Alemão Oswaldo Cruz