Prevention of Microvascular Complications in Overweight Diabetics With Surgery or Best Medicine

Study Overview
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Brief Summary
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Background: Diabetic kidney disease (DKD) is chronic and often progresses to kidney failure,heart disease and premature death. Unfortunately, the best medical therapies available for DKD today are ultimately unable to prevent its progression, especially in obese patients.Surgical rerouting of food within the gut with a gastric bypass operation (RYGB), improves diabetes and some of its complications. The investigators propose to investigate whether RYGB in combination with best medical therapy in patients with DKD and obesity prevent further deterioration of kidney function over a 3 years follow up period. Study design: This is an international collaboration with leading centres in Sweden and Switzerland in which100 obese type 2 diabetic patients with established DKD will volunteer to be randomly assigned to receive best medical therapy with RYGB or best medical therapy without surgery. Participants will be 18-65 years with type 2 diabetes and impaired kidney function. Yearly measurements of kidney function will then be done over a period of 3 years as a primary outcome to determine whether differences in DKD can be detectable. The study will also examine and compare a) safety of the interventions, b) the health economic impact on direct healthcare costs and Quality of Life in patients as well as c) the value of a new marker of DKD in determining which patients are most likely to benefit from surgery. Overall the study will strengthen the evidence base guiding clinical decisions about the usefulness of RYGB as an add on therapy to best medical therapy in stopping progressive DKD in patients with obesity and diabetes.

Official Title
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Prevention of Microvascular Complications in Overweight Diabetics With Surgery or Best Medicine; a Prospectivee, Randomized, Multicenter Study

Conditions
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Diabetic Kidney Disease

Intervention / Treatment
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* Procedure: Optimal medical treatment and surgery
* Procedure: Optimal medical treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • BMI 28 - 35 kg/m2 Age: 18-65 years, with T2DM Estimated glomerular filtration rate (eGFR; by MDRD) between 30 and 60mL/min/1.73m2 Urine albumin creatinine ratio (ACR) of at least 30mg/g (microalbuminuria) in first void urine on two separate days. Exclusion Criteria: • Type 1 diabetes or a positive GAD antibody test Known renal artery stenosis Renal impairment for reasons unrelated to diabetes Suspicion of glomerulonephritis as determined by urine sediment (>10 erythrocytes/visual field) Post-renal obstruction diagnosed by ultrasound Severe retinopathy (defined as high-risk proliferative diabetic retinopathy and severe visual loss according to the Early Treatment Diabetic Retinopathy Study Severity Scale) Severe DKD (CKD 4 or 5, requirement of renal replacement therapy such as dialysis or kidney transplantation) Severe neuropathy (peripheral neuropathy stage 3) Unacceptably high risk for general anesthesia Prior extensive intra-abdominal surgery making laparoscopy complicated Myocardial infarction, cerebrovascular accident, transient ischemic attack, coronary-artery bypass grafting or percutaneous transluminal coronary angioplasty within the previous 6 months Cardiac failure (NYHA stage > 2) Inability to stop smoking prior to inclusion Pregnancy or breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Optimal medical treatment and surgery<br>In the study 50 obese patients with CKD 3 andT2DM will be treated using the European Association for Study of Diabetes protocol in combination with RYGB surgery. | Procedure: Optimal medical treatment and surgery<br> <br> |
| Other: Optimal medical treatment<br>In the study 50 obese patients with CKD 3 andT2DM will be treated using the European Association for Study of Diabetes protocol | Procedure: Optimal medical treatment<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glomerular filtration rate | Renal function measurement by Iohexol clearance | Three years after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microvascular kidney damage | Microvascular kidney damage measured by Albumin/Creatinine Ratio | 3 years after intervention | 
| Glycaemic control | HbA1c and fasting plasma glucose measurements . Five day continuous glucose monitoring | 3 years after intervention | 
| peripheral nervous system function | Michigan Neuropathy Screening Instrument (MNSI) score, which includes two separate assessments: a lower extremity examination that includes inspection of the feet to identify deformities, dry skin, calluses, infection, fissure, or ulcers, and assessment of vibratory sensation and ankle reflexes | 3 years after intervention | 
| autonomic nervous system function | Autonomic neuropathy will be assessed with the RR intervals on ECG during deep breathing test | 3 years after intervention | 
| diabetic eyes complications | Using retinal photos and using the International Clinical Diabetic Retinopathy Disease Severity Scale | 3 years after intervention | 
| blood preassure | Blood pressure will be recorded with calibrated and validated electronic blood pressure equipment and appropriate sized cuff. Patients will sit in a chair in a quiet room for 5 minutes. | 3 years after intervention | 
| Lipids | Total cholesterol, low density lipoprotein, high density lipoprotein cholesterol and triglycerides will be measured | 3 years after intervention |