Clinical trial NCT01821508: Clinical Study on Metabolic Surgery Compared to the Best Clinical Treatment in Patients With Type 2 Diabetes Mellitus
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Complications of Diabetes Mellitus
Keywords: Gastroplasty, Diabetes Mellitus Type II, Obesity
Lead sponsor: Hospital Alemão Oswaldo Cruz
Sponsor class: OTHER
Collaborators: name: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
First posted: 2013-04-01
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: 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 ).
timeFrame: 12, 24 and 60 months
Secondary outcomes:
measure: Changes in diabetic retinopathy
timeFrame: 12, 24 and 60 months
measure: Changes in diabetic peripheral neuropathy
timeFrame: 12, 24 and 60 months
measure: Use of pharmacological therapy for type 2 diabetes mellitus
timeFrame: 12, 24 and 60 months
measure: Glycemic control
timeFrame: 12, 24 and 60 months
measure: Blood pressure control
timeFrame: 12, 24 and 60 months
measure: Lipids control
timeFrame: 12, 24 and 60 months
measure: Quality of life (SF-36)
timeFrame: 12, 24 and 60 months
measure: Changes in hepatic fibrosis
timeFrame: 12, 24 and 60 months
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Hospital Alemão Oswaldo Cruz
Study officials:
affiliation: Hospital Alemão Oswaldo Cruz
name: Ricardo V Cohen, MD. PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cohen RV, Pereira TV, Aboud CM, Petry TBZ, Lopes Correa JL, Schiavon CA, Pompilio CE, Pechy FNQ, da Costa Silva ACC, de Melo FLG, Cunha da Silveira LP, de Paris Caravatto PP, Halpern H, Monteiro FLJ, da Costa Martins B, Kuga R, Palumbo TMS, Docherty NG, le Roux CW. Effect of Gastric Bypass vs Best Medical Treatment on Early-Stage Chronic Kidney Disease in Patients With Type 2 Diabetes and Obesity: A Randomized Clinical Trial. JAMA Surg. 2020 Aug 1;155(8):e200420. doi: 10.1001/jamasurg.2020.0420. Epub 2020 Aug 19.
citation: Cohen RV, Pereira TV, Aboud CM, Caravatto PP, Petry TB, Correa JL, Schiavon CA, Correa M, Pompilio CE, Pechy FN, le Roux CW; MOMS Study Investigators. Microvascular Outcomes after Metabolic Surgery (MOMS) in patients with type 2 diabetes mellitus and class I obesity: rationale and design for a randomised controlled trial. BMJ Open. 2017 Jan 11;7(1):e013574. doi: 10.1136/bmjopen-2016-013574.