Randomized Study Comparing Metabolic Surgery With Intensive Medical Therapy to Treat Diabetic Kidney Disease

Diabetes Mellitus, Type 2 Clinical Trial

— OBESE-DKD  

Official title:

Open, Randomized, Unicenter Study Comparing Metabolic Surgery With Intensive Medical Therapy to Treat Diabetic Kidney Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04626323
• Other study ID #: OBESE-DKD
• Secondary ID: CAAE - 370134205
• Status: Recruiting
• Phase: Phase 2
• Start date: May 25, 2021
• Est. completion date: December 2024

Study information

• Verified date: May 2021
• Source: Hospital Alemão Oswaldo Cruz
• Contact: Cristina M Aboud, RN, MSc
• Phone: +551135491187
• Email: cmamedio[@]haoc.com.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Diabetic Nephropathies
• Kidney Disease, Chronic
• Kidney Diseases
• Kidney Injury
• Renal Insufficiency, Chronic

Intervention

Procedure:
• Roux-en-Y gastric bypass
Pneumoperitoneum closed with Veress needle Identification of Treitz angle Measurement of biliary loop (50 cm) Bowel transection with linear stapler (white load) Measurement of the alimentary limb (100 cm) Laterolateral Entero-anastomoses (white load) Construction of gastric pouch distant about 3 cm from the esophageal-gastric junction with stomach section in the small curvature. Linear cutting anastomosis (gastrojejunostomy) from about 1 to 1.2 cm Anastomosis integrity evaluation by methylene blue test and/or perioperative air. Expected surgical time: 60 minutes

Drug:
• Best medical treatment
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).

Locations

Country	Name	City	State
Brazil	Centro especializado em Obesidade e Diabetes do Hospital Alemão Oswaldo Cruz	Sao Paulo	São Paulo

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Alemão Oswaldo Cruz

Country where clinical trial is conducted

Brazil, 

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* Note: There are 60 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean differenceGlomerular filtration rate (GFR)	Mean difference in GFR between BMT and RYGB at the pre-specified time points of 12 and 36 months after randomization	At 12 and 36 months after randomization
Secondary	Change in twenty-four hour urinary albumin/protein excretion	Change in 24h urinary albumin/protein excretion	From baseline to 12 and 36 months
Secondary	Improvements in micro- or macroalbuminuria	Proportion of patients who achieve improvements in micro- or macroalbuminuria from baseline to 12 and 36 months	From baseline to 12 and 36 months
Secondary	Change in CKD stage and CKD prognostic risk	Change in CKD stage and CKD prognostic risk from baseline to month 12 and 36	From baseline to 12 and 36 months
Secondary	Change in GFR, eGFR and 24 hr creatinine clearance	Change in GFR, eGFR and 24 hr creatinine clearance from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Proportion of participants with =30%, =40%, and =50% reduction in GFR measurements	Proportion of participants with =30%, =40%, and =50% reduction in GFR measurements (GFR, eGFR and 24 hr creatinine clearance) from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Decline in eGFR, sustained low eGFR, kidney transplantation, maintenance dialysis, and kidney death	Time to occurrence of sustained % decline in eGFR, sustained low eGFR, kidney transplantation, maintenance dialysis, and kidney death	Time to occurrence (from baseline)
Secondary	Maintenance dialysis, kidney transplantation, kidney death, and GFR < 15 ml/min	Individual and composite endpoints of maintenance dialysis, kidney transplantation, kidney death, and GFR < 15 ml/min at 12 and 36 months	At 12 and 36 months after randomization
Secondary	Change in body weight	Change in body weight from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in body mass index	Change in body mass index from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in waist circumference	Change in waist circumference from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Medications to maintain optimal diabetes and blood pressure control	Number and dose of medications to maintain optimal diabetes and blood pressure control from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in fasting glucose	Change in fasting glucose from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in HbA1c	Change in HbA1c from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in basal insulin	Change in basal insulin from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in homeostasis model assessment (HOMA) scores	Change in homeostasis model assessment (HOMA) scores from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Remission in type 2 diabetes	Achievement of partial or complete remission in type 2 diabetes by months 12 and 36	At 12 and 36 months after randomization
Secondary	Change in blood pressure	Change in blood pressure from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Hypoglycemic adverse events	Number of patients with confirmed or symptomatic hypoglycemic adverse events from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Changes in total cholesterol, triglycerides, LDL and HDL levels	Changes in total cholesterol, triglycerides, LDL and HDL levels from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Number of participants achieving LDL < 100 mg/dL and HDL > 40mg/dL	Number of participants achieving LDL < 100 mg/dL and HDL > 40mg/dL from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Changes in serum calcium and phosphorus,	Changes in serum calcium and phosphorus from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in parathyroid hormone (PTH)	Change in parathyroid hormone (PTH) from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in mineral bone density	Change in mineral bone density from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in quality of life	Change in quality of life measured by SF-36 questionnaire from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Adverse events	Number of patients with adverse events from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Acute kidney injury	Number of episodes of acute kidney injury from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Adverse cardiovascular events (nonfatal stroke, nonfatal MI, cardiovascular death)	Composite of major adverse cardiovascular events (nonfatal stroke, nonfatal MI, cardiovascular death) from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Mortality	Total mortality from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Days hospitalized	Number of days hospitalized from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in urinary volume	Change in urinary volume from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in calcium and oxalate excretion	Change in calcium and oxalate excretion from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	High sensitivity c-reactive protein	Change in high sensitivity c-reactive protein from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in muscle strength	Change in muscle strength using one repetition maximum (1-RM) from baseline to months12 and 36	From baseline to 12 and 36 months
Secondary	Kidney volumes	Change in kidney volumes from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in ventricular mass	Change in left and right ventricular mass from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Change in ejection fraction	Change in left ventricular ejection fraction from baseline to months 12 and 36	From baseline to 12 and 36 months
Secondary	Costs of care and health care utilization	Costs of care and health care utilization from baseline to months 12 and 36	From baseline to 12 and 36 months

External Links

•   Obesity and Diabetes Center
•   Oswaldo Cruz German Hospital