Randomized Study Comparing Metabolic Surgery With Intensive Medical Therapy to Treat Diabetic Kidney Disease (OBESE-DKD)

Hospital Alemão Oswaldo Cruz

Status and phase: Enrolling; Phase 2

Conditions: Kidney Injury; Diabetes Mellitus, Type 2; Kidney Disease, Chronic

Treatments: Drug: Best medical treatment; Procedure: Roux-en-Y gastric bypass

Study type: Interventional

Funder types: Other

Identifiers

NCT04626323

CAAE - 37013420500000070 (Other Identifier)

OBESE-DKD

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 30 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

RYGB (intervention arm)

Experimental group

Description:

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.

Treatment:

Drug: Best medical treatment

Procedure: Roux-en-Y gastric bypass

BMT (control arm).

Active Comparator group

Description:

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.

Treatment:

Drug: Best medical treatment