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

NCT ID: NCT04626323

Last Updated: 2021-05-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-25

Study Completion Date

2024-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Diabetes Mellitus, Type 2 Kidney Disease, Chronic Kidney Injury

Keywords

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Diabetes Mellitus, Type 2 Diabetes Mellitus Obesity Metabolic surgery Gastric bypass Diabetic kidney disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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).
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Roux-en-Y gastric bypass

Intervention Type PROCEDURE

1. Pneumoperitoneum closed with Veress needle
2. Identification of Treitz angle
3. Measurement of biliary loop (50 cm)
4. Bowel transection with linear stapler (white load)
5. Measurement of the alimentary limb (100 cm)
6. Laterolateral Entero-anastomoses (white load)
7. Construction of gastric pouch distant about 3 cm from the esophageal-gastric junction with stomach section in the small curvature.
8. Linear cutting anastomosis (gastrojejunostomy) from about 1 to 1.2 cm
9. Anastomosis integrity evaluation by methylene blue test and/or perioperative air.

Expected surgical time: 60 minutes

Best medical treatment

Intervention Type DRUG

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).

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.

Group Type ACTIVE_COMPARATOR

Best medical treatment

Intervention Type DRUG

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).

Interventions

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Roux-en-Y gastric bypass

1. Pneumoperitoneum closed with Veress needle
2. Identification of Treitz angle
3. Measurement of biliary loop (50 cm)
4. Bowel transection with linear stapler (white load)
5. Measurement of the alimentary limb (100 cm)
6. Laterolateral Entero-anastomoses (white load)
7. Construction of gastric pouch distant about 3 cm from the esophageal-gastric junction with stomach section in the small curvature.
8. Linear cutting anastomosis (gastrojejunostomy) from about 1 to 1.2 cm
9. Anastomosis integrity evaluation by methylene blue test and/or perioperative air.

Expected surgical time: 60 minutes

Intervention Type PROCEDURE

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).

Intervention Type DRUG

Other Intervention Names

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RYGB BMT

Eligibility Criteria

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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
Minimum Eligible Age

30 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospital Alemão Oswaldo Cruz

OTHER

Sponsor Role lead

Responsible Party

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Ricardo Vitor Cohen, MD

Ricardo Vitor Cohen, MD, PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ricardo V Cohen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Oswaldo Cruz German Hospital

Locations

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Centro especializado em Obesidade e Diabetes do Hospital Alemão Oswaldo Cruz

São Paulo, São Paulo, Brazil

Site Status RECRUITING

Countries

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Brazil

Central Contacts

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Cristina M Aboud, RN, MSc

Role: CONTACT

Phone: +551135491187

Email: [email protected]

Facility Contacts

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Cristina M Aboud, RN, MSc

Role: primary

References

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Cummings DE, Cohen RV. Bariatric/Metabolic Surgery to Treat Type 2 Diabetes in Patients With a BMI <35 kg/m2. Diabetes Care. 2016 Jun;39(6):924-33. doi: 10.2337/dc16-0350.

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Batterham RL, Cummings DE. Mechanisms of Diabetes Improvement Following Bariatric/Metabolic Surgery. Diabetes Care. 2016 Jun;39(6):893-901. doi: 10.2337/dc16-0145.

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Friedman AN, Chang AR, Chuah LL, Favre GA, Grangeon-Chapon C, Lane KA, Li Y, le Roux CW, Lieske JC, Morales E, Porrini E, Chagnac A. Measurement, Estimation, and Correlates of the GFR before and after Bariatric Surgery. J Am Soc Nephrol. 2025 Jul 15. doi: 10.1681/ASN.0000000797. Online ahead of print. No abstract available.

Reference Type DERIVED
PMID: 40663401 (View on PubMed)

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Other Identifiers

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CAAE - 37013420500000070

Identifier Type: OTHER

Identifier Source: secondary_id

OBESE-DKD

Identifier Type: -

Identifier Source: org_study_id