Roux-en-Y Gastric Bypass for BMI 27-32 Type 2 Diabetes Versus Best Medical Treatment

Study Overview
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Brief Summary
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Investigators aim to show that Roux-en-Y Gastric Bypass (RYGB) is superior to best medical treatment in reaching well-defined treatment end points in Asian subjects of BMI 27-32 with type 2 Diabetes (DM2). Investigators also hope to show that successful RYGB will reduce resource utilization in the near term with similar projected reduction over the medium to long term.

Detailed Description
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40 subjects with DM2 will be recruited, randomised into two arms. The surgical arm will be subjected to RYGB. The medical arm will be treated maximally utilising the best means available and following internationally available protocol/guidelines. The study population will be subjected to a set of tests which is over and above the standard tests for similar groups of patients undergoing standard care (details below). Some test samples will be bio-banked. Treatment end points and follow up protocol will be the same for each treatment arm. The International Diabetic Federation (IDF) in 2011 recommended that bariatric surgery should be considered an alternative treatment option for those Asian DM2 subjects with BMI of 27 or above. Data for the effectiveness of Bariatric Surgery for those DM subjects with lower BMI is not as well established as those with higher BMI. There is scant good quality data, especially from Asian subjects. As their treatment is totally funded by the research project, subjects on the non surgical treatment arm will benefit from the more intense management of their disease with no restriction due to cost. The surgical arm will also be fully funded by the research project. They will be exposed to the standard risks associated with this type of surgery. Subjects in both arms will have to provide more blood and other samples than usual and has to follow visits protocol as close as possible. RYGB is a major surgical procedure, with significant potential complications; during the process of surgery and afterwards, both short and long term. Procedure related mortality is about 0.3%. Major complications that may require surgical intervention includes: anastomotic leakage about 3-4%, bleeding 3%, infection 3%, venous thrombo-embolism 1%. Some of these complications will require prolong hospitalisation. After surgery, loose stool, dumping syndrome, anastomotic ulcers can occur in less than 3%.Life long dietary supplement will be required. Longer term post surgical complications include intestinal obstruction due to adhesions or internal hernia, about 2%, further surgery may be needed. This risk is lifelong. Nutritional deficiencies, especially if not compliant with regular supplement intake, may occur. Drug allergies can occur; from simple rash to life threatening anaphylactic reaction. Blood taking can cause bruising, pain at the puncture site and sometimes fainting.

Official Title
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Roux-en-Y Gastric Bypass for BMI 27-32 Type 2 Diabetes vs Best Medical Treatment

Conditions
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Type II Diabetes in Subjects BMI 27 to 32

Intervention / Treatment
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* Procedure: Roux-en-Y Gastric Bypass (RYGB)
* Drug: Incretin analogues
* Drug: Xenical
* Drug: SGLT2 inhibitors
* Drug: DPP-4 Inhibitors


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Established diagnosis of DM2 = or < 10 years Age 21-65 BMI 27-32. HBA1c ≥ 8%, on maximum treatment from primary care physician At least one of the following co-morbidities on treatment: hypertension, hyperlipidaemia, micro/macro-proteinuria or ≤class I nephropathy, retinopathy. Exclusion Criteria: Subjects who had previous Bariatric surgery or extensive upper abdominal surgery Pregnant subjects. Nephropathy requiring dialysis Subjects who are not fit for general anaesthesia. Subjects who are unsuitable for RYGB for whatever reason, medical/surgical/psychological. Subjects who are unwilling or possibly unable to participate in the follow up process. Subjects who are reluctant to be randomised into the two study groups. Subjects who suffers from unstable psychiatric illness Subjects who are active substance abusers Glutamic acid decarboxylase antibody positive. fasting C-peptide < 300 pmol/L

Ages Eligible for Study
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Minimum Age: 21 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: Roux-en-Y Gastric Bypass (RYGB)<br>Roux-en-Y Gastric Bypass (RYGB) as per standard surgical protocol, with a 30 cc gastric pouch, 50 cm biliopancreatic limb and 100cm gastrointestinal limb. | Procedure: Roux-en-Y Gastric Bypass (RYGB)<br>* Roux-en-Y Gastric Bypass (RYGB) as per standard surgical protocol, with a 30 cc gastric pouch, 50 cm biliopancreatic limb and 100cm gastrointestinal limb.<br>|
| Active Comparator: Best Medical Treatment<br>Anti-diabetic medications provided (Mono- or Combination- therapy): Incretin analogues: Liraglutide up to 3 mg daily Or DPP-4 Inhibitors: Sitagliptin up to 100 mg daily, Linagliptin up to 5mg daily Xenical: Up to 120 mg tds SGLT2 inhibitors: Empagliflozin up to 25mg daily, Canagliflozin up to 300mg daily Participants will also take lipids & BP medications according to standard of care. | Drug: Incretin analogues<br>* Incretin analogues: Liraglutide up to 1.8 mg daily<br>* Other names: Liraglutide;Drug: Xenical<br>* Xenical: Up to 120 mg tds<br>* Other names: Orlistat;Drug: SGLT2 inhibitors<br>* SGLT2 inhibitors: Empagliflozin up to 25mg daily, Canagliflozin up to 300mg daily<br>* Other names: Canagliflozin;Drug: DPP-4 Inhibitors<br>* Sitagliptin up to 100 mg daily, Linagliptin up to 5mg daily<br>* Other names: Linagliptin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects achieving HBA1c of 6% without diabetic medication | The primary endpoint is to compare Roux-en-Y Gastric Bypass (RYGB) vs best medical treatment for Asian subjects of BMI 27-32 with poorly controlled type 2 Diabetes (DM2) in achieving a glycated haemoglobin level of 6% or less at 12 months after randomisation, and beyond till the end of the study period, without diabetic medications; and also systolic Blood Pressure of <130 mm HG, and LDL of <100mg/dl. | at 12 month after randomisation | 
| Number of subjects achieving systolic BP <130mm hg without antihypertension medication | The primary endpoint is to compare Roux-en-Y Gastric Bypass (RYGB) vs best medical treatment for Asian subjects of BMI 27-32 with poorly controlled type 2 Diabetes (DM2) in achieving a glycated haemoglobin level of 6% or less at 12 months after randomisation, and beyond till the end of the study period, without diabetic medications; and also systolic Blood Pressure of <130 mm HG, and LDL of <100mg/dl. | 12 months post randomisation | 
| number of subjects achieving LDL level of <100mg/dl without lipid lowering medication | The primary endpoint is to compare Roux-en-Y Gastric Bypass (RYGB) vs best medical treatment for Asian subjects of BMI 27-32 with poorly controlled type 2 Diabetes (DM2) in achieving a glycated haemoglobin level of 6% or less at 12 months after randomisation, and beyond till the end of the study period, without diabetic medications; and also systolic Blood Pressure of <130 mm HG, and LDL of <100mg/dl. | 12 months post randomisation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| fasting plasma glucose | Secondary end points include levels of fasting plasma glucose, fasting insulin, C-peptide, lipids, C-reactive protein (CRP), the homeostasis model assessment of insulin resistance (HOMA-IR) index, weight loss, blood pressure, adverse events, changes in medications, serum gut hormones and metabolic hormone levels. | 12 months after Randomisation | 
| Fasting Insulin | Secondary end points include levels of fasting plasma glucose, fasting insulin, C-peptide, lipids, C-reactive protein (CRP), the homeostasis model assessment of insulin resistance (HOMA-IR) index, weight loss, blood pressure, adverse events, changes in medications, serum gut hormones and metabolic hormone levels. | 12 months after radomisation | 
| serum c-peptide level | Secondary end points include levels of fasting plasma glucose, fasting insulin, C-peptide, lipids, C-reactive protein (CRP), the homeostasis model assessment of insulin resistance (HOMA-IR) index, weight loss, blood pressure, adverse events, changes in medications, serum gut hormones and metabolic hormone levels. | 12 months post randomisation | 
| serum lipid levels | Secondary end points include levels of fasting plasma glucose, fasting insulin, C-peptide, lipids, C-reactive protein (CRP), the homeostasis model assessment of insulin resistance (HOMA-IR) index, weight loss, blood pressure, adverse events, changes in medications, serum gut hormones and metabolic hormone levels. | 12 months post randomisation | 
| C-reactive protein level | Secondary end points include levels of fasting plasma glucose, fasting insulin, C-peptide, lipids, C-reactive protein (CRP), the homeostasis model assessment of insulin resistance (HOMA-IR) index, weight loss, blood pressure, adverse events, changes in medications, serum gut hormones and metabolic hormone levels. | 12 months post randolmisation | 
| change in medications usage | Secondary end points include levels of fasting plasma glucose, fasting insulin, C-peptide, lipids, C-reactive protein (CRP), the homeostasis model assessment of insulin resistance (HOMA-IR) index, weight loss, blood pressure, adverse events, changes in medications, serum gut hormones and metabolic hormone levels. | 12 months post randomisation | 
| changes in gut hormones levels | Secondary end points include levels of fasting plasma glucose, fasting insulin, C-peptide, lipids, C-reactive protein (CRP), the homeostasis model assessment of insulin resistance (HOMA-IR) index, weight loss, blood pressure, adverse events, changes in medications, serum gut hormones and metabolic hormone levels. | 12 months post randomisation | 
| changes in metabolic hormones level | Secondary end points include levels of fasting plasma glucose, fasting insulin, C-peptide, lipids, C-reactive protein (CRP), the homeostasis model assessment of insulin resistance (HOMA-IR) index, weight loss, blood pressure, adverse events, changes in medications, serum gut hormones and metabolic hormone levels. | 12 months post randomisation | 
| health resource utilisation | Secondary end points include levels of fasting plasma glucose, fasting insulin, C-peptide, lipids, C-reactive protein (CRP), the homeostasis model assessment of insulin resistance (HOMA-IR) index, weight loss, blood pressure, adverse events, changes in medications, serum gut hormones and metabolic hormone levels. On medium term follow up, we hope to evaluate the effect of successful DM2 improvement post surgery results in reduced resource utilization in the near term and a similar projected reduction over the long term. | 12 months post randomisation | 
| HOMA-IR | Secondary end points include levels of fasting plasma glucose, fasting insulin, C-peptide, lipids, C-reactive protein (CRP), the homeostasis model assessment of insulin resistance (HOMA-IR) index, weight loss, blood pressure, adverse events, changes in medications, serum gut hormones and metabolic hormone levels. | 12 months post randomisation | 
| Blood Pressure measurement |  | 12 months post randomisation | 
| number of adverse events | Secondary end points include levels of fasting plasma glucose, fasting insulin, C-peptide, lipids, C-reactive protein (CRP), the homeostasis model assessment of insulin resistance (HOMA-IR) index, weight loss, blood pressure, adverse events, changes in medications, serum gut hormones and metabolic hormone levels. | 12 months post randomisaiton | 
| Weight loss | Secondary end points include levels of fasting plasma glucose, fasting insulin, C-peptide, lipids, C-reactive protein (CRP), the homeostasis model assessment of insulin resistance (HOMA-IR) index, weight loss, blood pressure, adverse events, changes in medications, serum gut hormones and metabolic hormone levels. | 12 months post randomisation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, surgical treatment, medical treatment