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

NCT ID: NCT01974544

Last Updated: 2013-11-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-31
• Study Completion Date: 2016-12-31

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?

Detailed Description

Currently 205 million patients in the world suffer with Type 2 diabetes and severe and complex obesity. The obesity is defined as a body mass index above 30 kg/m2 with life or limb threatening co-morbidities.

The bariatric surgery increase in worldwide, but their effects on the microvascular complications of T2DM have never been the focus of a randomised controlled clinical trial.

To address this research question a three arms on randomised controlled clinical trial comparing gastric bypass surgery, sleeve gastrectomy and modern best medical care is required to investigate differences in long term glycaemia and microvascular complications of T2DM.

This is a prospective intervention study on patients with T2DM and obesity undergoing gastric bypass surgery, sleeve gastrectomy or non surgical best medical care. Patients will have T2DM for more than 2 years and have or be at high risk of developing kidney damage. Patients will be recruited from specialist medical and surgical clinics.

We expect to screen approximately 300 patients to allow 75 to be randomized. Twenty five subjects with kidney damage or high risk of kidney damage secondary to T2DM will undergo gastric bypass surgery. Another 25 sleeve gastrectomy and the final 25 will be treated using the American Diabetes Association protocol. Patients with HbA1c ≥9.0% will undergo individualised optimisation of glycaemia as this should improve surgical outcomes. Particular attention will be given to the avoidance of hypoglycaemia. Patients' other risk factors (including hypertension and dyslipidaemia) will be optimised based on the International Diabetes Federation guidelines.

The clinical endpoints that will be assessed are: renal function, peripheral and autonomic nervous system function, the retina, of direct healthcare cost, glycaemic control, blood pressure, lipids, quality of life, postprandial responses, treatment complications.

Conditions

Type 2 Diabetes

Keywords

diabetes complications; metabolic surgery; Intensive medicines

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Best medical treatment

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.

Group Type: EXPERIMENTAL

Best medical treatment

Intervention Type: 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.

General interventions for all groups: blood presure

Intervention Type: 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.

General interventions for all groups: dysilipidemia

Intervention Type: 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).

General interventions for all groups: lifestyle

Intervention Type: 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.

gastric bypass surgery

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.

Group Type: EXPERIMENTAL

gastric bypass

Intervention Type: 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

General interventions for all groups: blood presure

Intervention Type: 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.

General interventions for all groups: dysilipidemia

Intervention Type: 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).

General interventions for all groups: lifestyle

Intervention Type: 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.

sleeve gastrectomy

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.

Group Type: EXPERIMENTAL

sleeve gastrectomy

Intervention Type: 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

General interventions for all groups: blood presure

Intervention Type: 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.

General interventions for all groups: dysilipidemia

Intervention Type: 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).

General interventions for all groups: lifestyle

Intervention Type: 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.

Interventions

Best medical treatment

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.

Intervention Type: DRUG

gastric bypass

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

Intervention Type: PROCEDURE

sleeve gastrectomy

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

Intervention Type: PROCEDURE

General interventions for all groups: blood presure

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.

Intervention Type: DRUG

General interventions for all groups: dysilipidemia

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).

Intervention Type: DRUG

General interventions for all groups: lifestyle

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.

Intervention Type: BEHAVIORAL

Other Intervention Names

Non surgical interventions; Glycemic control drugs; Management elevated blood pressure in patients with T2DM; Management of dyslipidemia; Therapeutic lifestyle modification

Eligibility Criteria

Inclusion Criteria

1. Type 2 diabetes with HbA1c > 7%

2. Duration of diabetes of more than 2 years

3. The glomerular filtration rate (GFR) > 30 ml/min per 1.73 m2

4. BMI < 35 kg/m2

5. Age 18-65

6. Established microalbuminuria or at high risk of microalbuminuria

Exclusion Criteria

1. Type 1 diabetes or positive Glutamic acid decarboxylase antibodies (Anti-GAD)

2. BMI >35 kg/m2

3. 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)

4. Unacceptably high risk for general anaesthesia.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pontificia Universidad Catolica de Chile

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boza Camilo, MD surgeon

Role: PRINCIPAL_INVESTIGATOR

Pontificia Universidad Catolica de Chile

Locations

Pontificia Universidad Católica de Chile

Santiago, Santiago Metropolitan, Chile

Site Status: RECRUITING

Countries

Chile

Central Contacts

Castillo Alejandra

Role: CONTACT

Phone: 56223543257

Email: macastia@uc.cl

Vega Andrea

Role: CONTACT

Phone: 56223543879

Email: abvega@uc.cl

Facility Contacts

Castillo Alejandra, Nurse

Role: primary

Vega Andrea, Nurse

Role: backup

Other Identifiers

11-141

Identifier Type: -

Identifier Source: org_study_id