Clinical Study on Metabolic Surgery Compared to the Best Clinical Treatment in Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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This is a prospective, open, randomized study involving 100 patients with microvascular complications of type 2 diabetes mellitus and obesity, who will undergo gastric bypass (Roux-en-Y gastric bypass ARM A) or receive best medical treatment (ARM B, control arm). The aim of this study is to evaluate the effects of Roux-en-Y gastric bypass in the control of diabetic nephropathy in diabetic patients with BMI between 30 and 35 kg/m2. The medical community is confronted with many different studies using various methodologies to investigate the best pharmacological treatment for type 2 diabetes mellitus. The treatment algorithm offers several different options according to the stage of the disease (which is different in each study). In addition, new drugs are being developed over the years, but are not always a guarantee of effective type 2 diabetes mellitus control [MENDES, 2010]. Furthermore, these drugs do not prevent the development of this disease, consequently increasing the risks of microvascular and macrovascular complications. Conversely, there is considerable evidence that surgery can be an adequate tool to promote type 2 diabetes mellitus remission in patients who are unresponsive to clinical treatment. Gastric bypass surgery is one of the most popular bariatric surgeries in the world, but its effects on microvascular and macrovascular complications of type 2 diabetes mellitus have not been established. Specialists suggest that the rapid and uncontrollable decrease in blood glucose adds to the concern that the surgery may paradoxically cause exacerbation of microvascular complications [LEOW, 2005], whereas gradual improvement in blood glucose before gastric bypass surgery may prevent this paradoxical worsening, leading to an interruption of this process, or even retinopathy, nephropathy, and neuropathy remission. However, there are no studies comparing the results of these two types of treatment (clinical vs. surgical) in a similar population and assessing the development of microvascular complications of type 2 diabetes mellitus. Therefore, in order to clarify such doubts, it is necessary and extremely desirable to conduct a randomized controlled trial comparing gastric bypass with the best and most modern clinical treatment. Its findings could have a direct impact on hundreds of millions of diabetics by allowing the inclusion of surgical treatment as a safe and feasible therapeutic option for a significant portion of these patients.

Detailed Description
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Intervention of Roux-En-Y gastric bypass surgery versus best medical treatment in control or reduces microvascular complications such as retinopathy, microalbuminuria and neuropathic.

Official Title
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Prospective, Open,Randomized, Unicentre Study Comparing Roux-en-Y Gastric Bypass With the Best Clinical Treatment Regarding Improvement of Microvascular Complications of Type 2 Diabetes Mellitus in Obese Patients.

Conditions
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Complications of Diabetes Mellitus

Intervention / Treatment
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* Other: Clinical Treatment
* Procedure: Roux-En-Y gastric bypass surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female adult patients with microalbuminuria (more than 30 mg and less than 300 mg or more of urinary albumin per 24 hours), with or without other microvascular complications of type 2 diabetes mellitus, receiving pharmacological treatment for the disease, which may or may not include the use of insulin. Age between 18-65 years BMI between 30 and 35 Kg/m2 15-year or less after type 2 diabetes mellitus diagnosis Negative anti-glutamic acid decarboxylase Fasting C-peptide higher than 1 ng/ml, increasing in the postprandial period (two hours after mixed meal, ENSURE plus approximately 500 Kcal) Exclusion Criteria: Patient's refusal to participate Autoimmune diabetes mellitus Previous abdominal surgeries that may make surgery more difficult, increasing the surgical risk Previous malabsorptive and restrictive surgeries Pregnant women and nursing mothers Recent history of neoplasia (< 5 years), except for non-melanoma skin neoplasms History of liver disease - liver cirrhosis -, active chronic hepatitis, active hepatitis B and hepatitis C Malabsorptive syndromes and inflammatory bowel disease Cardiovascular event (acute myocardial infarction, acute coronary syndrome, angioplasty, or bypass in the last 6 months) Angina Pulmonary embolism or severe thrombophlebitis in the last 2 years Positive HIV serum testing Psychiatric disorders, including dementia, active psychosis, severe depression, history of suicide attempts, use of illicit drugs, and excessive alcohol consumption in the last 12 months Uncontrolled coagulopathy Patients with severe retinopathy, nephropathy, and neuropathy (defined as high risk/advanced proliferative retinopathy or amaurosis; stage 5 of chronic kidney disease defined by glomerular filtration rate, patients who need dialysis or renal transplantation; stage 3 of peripheral neuropathy) Patients who participated in other clinical trials in the past 30 days.

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: Clinical treatment<br>Best and most modern clinical treatment of type 2 diabetes mellitus. | Other: Clinical Treatment<br>* metabolic surgery for diabetes and weight control<br>* Other names: lifestyle changes for obesity;|
| Active Comparator: Roux-En-Y gastric bypass surgery<br>A metabolic surgery consists of any surgical procedure in which there is any anatomical alteration in the gastrointestinal tract by means of a diversion of food passage, resulting in improved metabolic control in patients with type 2 diabetes mellitus [SCHULMAN, 2009]. | Procedure: Roux-En-Y gastric bypass surgery<br>* laparoscopic surgical procedure with Endoscopic Surgical Stapler<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint will be the proportion of patients that present normalization of the albumin/creatinine ratio in isolated urine samples (normal value considered as an albumin/creatinine ratio of less than 30 μg/mg ). | Number of participants achieving remission Titrating the relation of urinary albumin/creatinine | 12, 24 and 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in diabetic retinopathy | Number of patients achieving resolution or reduction in the degree of retinopathy and/or macular oedema (severity scale) | 12, 24 and 60 months | 
| Changes in diabetic peripheral neuropathy | Number of patients with new or worsening of neuropathy | 12, 24 and 60 months | 
| Use of pharmacological therapy for type 2 diabetes mellitus | Number of medications necessary for targeting euglycaemia | 12, 24 and 60 months | 
| Glycemic control | Number of patients achieving fasting glucose level < 100 and HbA1c < 6.5% | 12, 24 and 60 months | 
| Blood pressure control | Number of patients achieving systolic blood pressure <130 mm Hg and diastolic <80 mm Hg | 12, 24 and 60 months | 
| Lipids control | Number of patients with LDL<100 or <70 mg/dL in patients with previous cardiovascular events; HDL>50 mg/dL and triglycerides <150 mg/dL | 12, 24 and 60 months | 
| Quality of life (SF-36) | SF-36 questionnaire | 12, 24 and 60 months | 
| Changes in hepatic fibrosis | Reduction of hepatic elastographic resistance | 12, 24 and 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastroplasty, Diabetes Mellitus Type II, Obesity