Prevention and Treatment Of Diabetes Complications With Gastric Surgery or Intensive Medicines

NCT01974544 | Unknown DMC

• 1 other identifier: 11-141
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

The obesity and type 2 diabetes mellitus (T2DM) are among the most threatening health crisis for the 21st century. Currently, it is estimated that there are 205 million people with T2DM worldwide. Chile has a similar magnitude of problem with the prevalence of diabetes increasing from 6.3% in 2003 to 9.4% in 2010. T2DM is a complex disease characterized by hyperglycemia, insulin resistance and a relative β-cell failure. Well-known studies for the treatment of T2DM (ADVANCE trial) showed that intensive medical treatment significantly reduces the complication of diabetes. On the other hand, less than 40% of patients with T2DM achieve a metabolic control of diabetes, despite medical treatment. Recently, bariatric surgery has emerged as an effective treatment for T2DM. Data from different sources has shown that Roux-en-Y Gastric Bypass (RYGB) can place T2DM into remission. More recently, Sleeve Gastrectomy (SG) has been shown to also impact metabolically and hence also emerged as an attractive T2DM-controlling bariatric procedure with fewer complications than RYGB. Recently, the International Federation for Diabetes has supported the use gastrointestinal surgery initially developed for morbid obesity as an option to treat patients with diabetes. In the current proposal the investigators aim to address several issues concerning metabolic surgery and the ability of the most common bariatric procedures performed to control diabetes. The investigators are proposing a prospective randomized trial comparing RYGB, SG and the best medical treatment availed for the T2DM in poorly control patients with the primary endpoint being 36 month glycemic control (patients achieving HbA1C \< 6.5%, normal glucose levels not requiring medication). The main working hypothesis is that RYGB and SG achieves better glycemic control than the best treatment availed for the T2DM based on more effective mechanisms to enhance insulin secretion, insulin sensitivity, lipid metabolism and blood pressure control. The goals are, 1) Is gastric bypass surgery and sleeve gastrectomy safe for the microvascular complications of T2DM?; 2) Can gastric bypass, sleeve gastrectomy surgery and intensive non surgical treatment reverse or reduce the progression of microvascular complications of T2DM?; and 3) Can gastric bypass and sleeve gastrectomy realize a return on investment within 2 years in patients with type 2 diabetes who are at risk of developing or deteriorating microvascular complications?

Conditions

Type 2 Diabetes

Keywords

diabetes complications; metabolic surgery; Intensive medicines

Outcome Measures

Primary Outcomes (3)

• Change in the microvascular complications of type 2 diabetes, specifically diabetic kidney disease

  These outcome will be measured through the glomerular filtration rate (GFR), (MDRD-1 equation: GFR (expressed in ml/min/1.73 m2), and Albuminuria (ACR (mg/g).

  baseline at 1 month before the intervention and 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36 month after intervention

• Change in the microvascular complications of type 2 diabetes, specifically Retinopathy.

  This will be measured through assessment by ophthalmologist.

  baseline at 1 month before the intervention, 12 y 24 month after intervention

• Change in the microvascular complications of type 2 diabetes, specifically peripheral and sympathic neuropathy.

  This will be measured through assessment nerve conduction, sensory nerve conduction, motor nerve conduction, sympathic skin response.

  baseline at 1 month before the intervention, 12, 24 y 36 month

Secondary Outcomes (5)

• Assessment of the optimization of the metabolic control, defined by the International Diabetes Federation

  baseline at 1 month before the intervention and 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36 month after the intervention

• Assessment of treatment complications

  1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36 month after intervention

• Assessment of the quality of life.

  baseline at 1 month before the intervention and 3, 6, 12, and 24 month after the intervention

• Assessment of macrovascular events

  baseline at 1 month before the intervention and 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36 month after the intervention

• How many patients not requiring antidiabetic agents

  baseline 1 month after intervention, and at 6, 12, 18, 24, 30, and 36 month after intervention

Study Arms (3)

Best medical treatment

EXPERIMENTAL

Fifty obese patients with kidney damage or high risk of kidney damage secondary to T2DM will will be treated using the American Diabetes Association protocol. Also this arm will be treated like: General interventions for all groups: blood presure, General interventions for all groups: dysilipidemia and General interventions for all groups: lifestyle establishes.

Drug: Best medical treatment; Drug: General interventions for all groups: blood presure; Drug: General interventions for all groups: dysilipidemia; Behavioral: General interventions for all groups: lifestyle

gastric bypass surgery

EXPERIMENTAL

Fifty obese patients with kidney damage or high risk of kidney damage secondary to T2DM will undergo gastric bypass surgery, in the conventional procedure. Also this arm will be treated like: General interventions for all groups: blood presure, General interventions for all groups: dysilipidemia and General interventions for all groups: lifestyle establishes.

Procedure: gastric bypass; Drug: General interventions for all groups: blood presure; Drug: General interventions for all groups: dysilipidemia; Behavioral: General interventions for all groups: lifestyle

sleeve gastrectomy

EXPERIMENTAL

Fifty obese patients with kidney damage or high risk of kidney damage secondary to T2DM will undergo sleeve gastrectomy surgery, in the conventional procedure. Also this arm will be treated like: General interventions for all groups: blood presure, General interventions for all groups: dysilipidemia and General interventions for all groups: lifestyle establishes.

Procedure: sleeve gastrectomy; Drug: General interventions for all groups: blood presure; Drug: General interventions for all groups: dysilipidemia; Behavioral: General interventions for all groups: lifestyle

Interventions

Best medical treatment DRUG

If patients are unable to maintain their haemoglobin A1c (HbA1c) values below 6.5% on diet alone, treatment with metformin 1g twice daily will be started. If HbA1c remains above 7.0% then liraglutide 0.6 mg once daily (with a subsequent increases to 1.2 mg and 1.8 mg once daily). If liraglutide is not tolerated then a Dipeptidyl peptidase IV inhibitor (sitagliptin, saxagliptin, linagliptin) or pioglitazone will be considered. If HbA1c remains above 7.5% long acting insulin analogues such as detemir o glargine will be added. If insulin is started liraglutide can be stopped. The insulin dose will be adjusted according to the morning fasting blood glucose concentration. Finally, Fast-acting meal time insulin (lispro, aspart or glulisine) will be added if glycemic goal is not achieved. Repaglinide can be considered in patients with significant renal impairment and in patients who refused insulin treatment.

Also known as: Non surgical interventions, Glycemic control drugs

Best medical treatment

gastric bypass PROCEDURE

For the gastric bypass, the gastric pouch will be adjusted to a volume of 15-20 ml. The alimentary limb will be a standard 150 cm and the biliopancreatic limb 50 cm. A hand-sewn gastro-jejunal anastomosis will be performed over a 34 French bougie

gastric bypass surgery

sleeve gastrectomy PROCEDURE

The sleeve gastrectomy will be done using laparoscopic staplers over a 34 French bougie.The greater curvature will be dissected 4 cm proximal to the pylorus leaving the antrum. Short gastric vessels will be dissected using the harmonic scalpel up to the gastro-esophageal junction. The stapler will be reinforced. The resected stomach will be removed in a plastic bag through the left flank trocar

sleeve gastrectomy

General interventions for all groups: blood presure DRUG

Patients will receive an angiotensin-converting-enzyme (ACE) inhibitor or angiotensin II receptor antagonists (ARA II) to meet strict blood pressure targets of the ADA / European Association for Study of Diabetes (EASD) or in the presence of micro or macroalbuminuria. In addition to ACE inhibitors (or if there were side-effects, an angiotensin-II receptor antagonist), calcium antagonist, diuretics or Beta blockers can be added as needed. Aspirin 100 mg daily will be used for secondary prevention in patients with a history of ischaemic cardiovascular disease.

Also known as: Management elevated blood pressure in patients with T2DM

Best medical treatment; gastric bypass surgery; sleeve gastrectomy

General interventions for all groups: dysilipidemia DRUG

Raised fasting serum cholesterol concentrations (greater than 4.5 mmol/L) or combined dyslipidaemias will be treated with atorvastatin 10-80mg once daily. Gemfibrozilo or fenofibrate once daily can be used for isolated hypertriglyceridaemia (fasting serum triglyceride concentration \>4.0 mmol/L), or fenofibrate can be added to statin treatment if the fasting serum triglyceride concentration was also raised (\>4.0 mmol/L).

Also known as: Management of dyslipidemia

Best medical treatment; gastric bypass surgery; sleeve gastrectomy

General interventions for all groups: lifestyle BEHAVIORAL

Exercise is an important part of the diabetes management plan. The ADA recommendations for the adults with diabetes is at least 150 min/week of moderate-intensity aerobic physical activity (50-70% of maximum heart rate), with no more than two consecutive days without exercise. A kinesiologist will design an individual plan of physical training for each patient. Also, a nutritionist will be design an individual dietitian plan, this plan should be formulated as a collaborative therapeutic alliance among the patient and family, physician, and other members of the health care team.

Also known as: Therapeutic lifestyle modification

Best medical treatment; gastric bypass surgery; sleeve gastrectomy

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 2 diabetes with HbA1c \> 7%
• Duration of diabetes of more than 2 years
• The glomerular filtration rate (GFR) \> 30 ml/min per 1.73 m2
• BMI \< 35 kg/m2
• Age 18-65
• Established microalbuminuria or at high risk of microalbuminuria

You may not qualify if:

• Type 1 diabetes or positive Glutamic acid decarboxylase antibodies (Anti-GAD)
• BMI \>35 kg/m2
• End stage retinopathy, nephropathy or neuropathy (defined as high risk/advanced proliferative retinopathy on the Early Treatment Diabetic Retinopathy Study Severity Scale or blindness, Stage 5 chronic kidney disease, patients requiring dialysis or transplantation, Stage 3 peripheral neuropathy)
• Unacceptably high risk for general anaesthesia.

Sponsors & Collaborators

• Pontificia Universidad Catolica de Chile: lead

Study Sites (1)

Pontificia Universidad Católica de Chile

Santiago, Santiago Metropolitan, 8330033, Chile

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Complications

Interventions

Gastric Bypass

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Bariatric Surgery; Bariatrics; Obesity Management; Therapeutics; Gastroenterostomy; Anastomosis, Surgical; Surgical Procedures, Operative; Digestive System Surgical Procedures

Study Officials

• Boza Camilo, MD surgeon

  Pontificia Universidad Catolica de Chile

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Castillo Alejandra

CONTACT

56223543257; macastia@uc.cl

Vega Andrea

CONTACT

56223543879; abvega@uc.cl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2013
• First Posted: November 1, 2013
• Study Start: May 1, 2013
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2016
• Last Updated: November 1, 2013

Record last verified: 2013-10

Locations

CL (1)