Clinical trial NCT01974544: Prevention and Treatment Of Diabetes Complications With Gastric Surgery or Intensive Medicines
Official title: Prevention and Treatment Of Diabetes Complications With Gastric Surgery or Intensive Medicines
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Type 2 Diabetes
Keywords: diabetes complications
metabolic surgery
Intensive medicines
Lead sponsor: Pontificia Universidad Catolica de Chile
Sponsor class: OTHER
First posted: 2013-11-01
Enrollment: 150
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: 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.

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.

Primary outcomes:
measure: Change in the microvascular complications of type 2 diabetes, specifically diabetic kidney disease
timeFrame: baseline at 1 month before the intervention and 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36 month after intervention
measure: Change in the microvascular complications of type 2 diabetes, specifically Retinopathy.
timeFrame: baseline at 1 month before the intervention, 12 y 24 month after intervention
measure: Change in the microvascular complications of type 2 diabetes, specifically peripheral and sympathic neuropathy.
timeFrame: baseline at 1 month before the intervention, 12, 24 y 36 month
Secondary outcomes:
measure: Assessment of the optimization of the metabolic control, defined by the International Diabetes Federation
timeFrame: baseline at 1 month before the intervention and 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36 month after the intervention
measure: Assessment of treatment complications
timeFrame: 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36 month after intervention
measure: Assessment of the quality of life.
timeFrame: baseline at 1 month before the intervention and 3, 6, 12, and 24 month after the intervention
measure: Assessment of macrovascular events
timeFrame: 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
measure: How many patients not requiring antidiabetic agents
timeFrame: baseline 1 month after intervention, and at 6, 12, 18, 24, 30, and 36 month after intervention
Other outcomes:
Locations:
city: Santiago
country: Chile
facility: Pontificia Universidad Católica de Chile
state: Región Metropolitana
Study officials:
affiliation: Pontificia Universidad Catolica de Chile
name: Boza Camilo, MD surgeon
role: PRINCIPAL_INVESTIGATOR
References: