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

• ClinicalTrials.gov Identifier: NCT02041234
• Recruitment Status: Recruiting
• First Posted: January 22, 2014
• Last Update Posted: December 11, 2018
• Sponsor: Khoo Teck Puat Hospital
• Information provided by (Responsible Party): Anton Cheng, Khoo Teck Puat Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Type II Diabetes in Subjects BMI 27 to 32	Procedure: Roux-en-Y Gastric Bypass (RYGB); Drug: Incretin analogues; Drug: Xenical; Drug: SGLT2 inhibitors; Drug: DPP-4 Inhibitors	Phase 4

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Roux-en-Y Gastric Bypass for BMI 27-32 Type 2 Diabetes vs Best Medical Treatment
• Study Start Date: February 2014
• Estimated Primary Completion Date: March 2020
• Estimated Study Completion Date: March 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Roux-en-Y Gastric Bypass (RYGB); 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); 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.
Active Comparator: Best Medical Treatment; 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; Incretin analogues: Liraglutide up to 1.8 mg daily; Other Name: Liraglutide; Drug: Xenical; Xenical: Up to 120 mg tds; Other Name: Orlistat; Drug: SGLT2 inhibitors; SGLT2 inhibitors: Empagliflozin up to 25mg daily, Canagliflozin up to 300mg daily; Other Names: Empagliflozin; Canagliflozin; Drug: DPP-4 Inhibitors; Sitagliptin up to 100 mg daily, Linagliptin up to 5mg daily; Other Names: Sitagliptin; Linagliptin

Outcome Measures

Primary Outcome Measures :

1. Number of subjects achieving HBA1c of 6% without diabetic medication [ Time Frame: at 12 month after randomisation ]
   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.
2. Number of subjects achieving systolic BP <130mm hg without antihypertension medication [ Time Frame: 12 months post randomisation ]
   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.
3. number of subjects achieving LDL level of <100mg/dl without lipid lowering medication [ Time Frame: 12 months post randomisation ]
   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.

Secondary Outcome Measures :

1. fasting plasma glucose [ Time Frame: 12 months after Randomisation ]
   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.
2. Fasting Insulin [ Time Frame: 12 months after radomisation ]
   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.
3. serum c-peptide level [ Time Frame: 12 months post randomisation ]
   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.
4. serum lipid levels [ Time Frame: 12 months post randomisation ]
   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.
5. C-reactive protein level [ Time Frame: 12 months post randolmisation ]
   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.
6. change in medications usage [ Time Frame: 12 months post randomisation ]
   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.
7. changes in gut hormones levels [ Time Frame: 12 months post randomisation ]
   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.
8. changes in metabolic hormones level [ Time Frame: 12 months post randomisation ]
   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.
9. health resource utilisation [ Time Frame: 12 months post randomisation ]

   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.

10. HOMA-IR [ Time Frame: 12 months post randomisation ]
    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.
11. Blood Pressure measurement [ Time Frame: 12 months post randomisation ]
12. number of adverse events [ Time Frame: 12 months post randomisaiton ]
    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.
13. Weight loss [ Time Frame: 12 months post randomisation ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Established diagnosis of DM2 = or < 10 years
2. Age 21-65
3. BMI 27-32.
4. HBA1c ≥ 8%, on maximum treatment from primary care physician
5. At least one of the following co-morbidities on treatment: hypertension, hyperlipidaemia, micro/macro-proteinuria or ≤class I nephropathy, retinopathy.

Exclusion Criteria:

1. Subjects who had previous Bariatric surgery or extensive upper abdominal surgery
2. Pregnant subjects.
3. Nephropathy requiring dialysis
4. Subjects who are not fit for general anaesthesia.
5. Subjects who are unsuitable for RYGB for whatever reason, medical/surgical/psychological.
6. Subjects who are unwilling or possibly unable to participate in the follow up process.
7. Subjects who are reluctant to be randomised into the two study groups.
8. Subjects who suffers from unstable psychiatric illness
9. Subjects who are active substance abusers
10. Glutamic acid decarboxylase antibody positive.
11. fasting C-peptide < 300 pmol/L

Contacts and Locations

Contacts

Contact: Anton Cheng, MBBS; 6602 3305; cheng.anton.ks@alexandrahealth.com.sg

Contact: Bernice Li Ting Tan; 6602 3169; tan.bernice.lt@alexandrahealth.com.sg

Locations

Singapore

Khoo Teck Puat Hospital; Recruiting

Singapore, Singapore, 768828

Contact: Bernice Tan +65 6602 3169 tan.bernice.lt@alexandrahealth.com.sg

Principal Investigator: Anton Cheng, MBBS

Sub-Investigator: Chee Fang Sum, MBBS

Sub-Investigator: Su Chi Lim, MBBS

Sub-Investigator: Tavintharan Subramaniam, MBBS

Sub-Investigator: Nitish Mishra, MBBS

Sub-Investigator: Ester Yeoh, MBBS

Sub-Investigator: Chun Hai Tan, MBBS

Sub-Investigator: Benjamin Chih Chiang Lam, MBBS

Sub-Investigator: Thazin Ma, MBBS

Sub-Investigator: Michael Wong, MBBS

Sponsors and Collaborators

Khoo Teck Puat Hospital

Investigators

• Principal Investigator: Anton Cheng, MBBS; Khoo Teck Puat Hospital
• Principal Investigator: Su Chi Lim, MBBS, PhD; Khoo Teck Puat Hospital

More Information

Publications:

Colquitt JL, Picot J, Loveman E, Clegg AJ. Surgery for obesity. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD003641. doi: 10.1002/14651858.CD003641.pub3. Review. Update in: Cochrane Database Syst Rev. 2014;8:CD003641.

Buchwald H, Estok R, Fahrbach K, Banel D, Jensen MD, Pories WJ, Bantle JP, Sledge I. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med. 2009 Mar;122(3):248-256.e5. doi: 10.1016/j.amjmed.2008.09.041. Review.

Sjöström L, Narbro K, Sjöström CD, Karason K, Larsson B, Wedel H, Lystig T, Sullivan M, Bouchard C, Carlsson B, Bengtsson C, Dahlgren S, Gummesson A, Jacobson P, Karlsson J, Lindroos AK, Lönroth H, Näslund I, Olbers T, Stenlöf K, Torgerson J, Agren G, Carlsson LM; Swedish Obese Subjects Study. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007 Aug 23;357(8):741-52.

Dixon JB, Zimmet P, Alberti KG, Rubino F; International Diabetes Federation Taskforce on Epidemiology and Prevention. Bariatric surgery: an IDF statement for obese Type 2 diabetes. Diabet Med. 2011 Jun;28(6):628-42. doi: 10.1111/j.1464-5491.2011.03306.x.

Pories WJ, Swanson MS, MacDonald KG, Long SB, Morris PG, Brown BM, Barakat HA, deRamon RA, Israel G, Dolezal JM, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg. 1995 Sep;222(3):339-50; discussion 350-2.

Schauer PR, Kashyap SR, Wolski K, Brethauer SA, Kirwan JP, Pothier CE, Thomas S, Abood B, Nissen SE, Bhatt DL. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med. 2012 Apr 26;366(17):1567-76. doi: 10.1056/NEJMoa1200225. Epub 2012 Mar 26.

Mingrone G, Panunzi S, De Gaetano A, Guidone C, Iaconelli A, Leccesi L, Nanni G, Pomp A, Castagneto M, Ghirlanda G, Rubino F. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med. 2012 Apr 26;366(17):1577-85. doi: 10.1056/NEJMoa1200111. Epub 2012 Mar 26.

Cohen RV, Pinheiro JC, Schiavon CA, Salles JE, Wajchenberg BL, Cummings DE. Effects of gastric bypass surgery in patients with type 2 diabetes and only mild obesity. Diabetes Care. 2012 Jul;35(7):1420-8. doi: 10.2337/dc11-2289.

• Responsible Party: Anton Cheng, Dr Anton Cheng, Khoo Teck Puat Hospital
• ClinicalTrials.gov Identifier: NCT02041234
• Other Study ID Numbers: Bariatric Surgery RCT
• First Posted: January 22, 2014
• Last Update Posted: December 11, 2018
• Last Verified: December 2018

Keywords provided by Anton Cheng, Khoo Teck Puat Hospital:

Diabetes; surgical treatment; medical treatment

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Sitagliptin Phosphate; Liraglutide; Empagliflozin; Linagliptin; Canagliflozin; Dipeptidyl-Peptidase IV Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Orlistat; Incretins; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-Obesity Agents; Lipid Regulating Agents