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

Type II Diabetes in Subjects BMI 27 to 32 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02041234
• Other study ID #: Bariatric Surgery RCT
• Status: Completed
• Phase: Phase 4
• Start date: February 2014
• Est. completion date: June 2022

Study information

• Verified date: June 2022
• Source: Khoo Teck Puat Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: June 2022
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type II Diabetes in Subjects BMI 27 to 32

Intervention

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.

Drug:
• Incretin analogues
Incretin analogues: Liraglutide up to 1.8 mg daily
• Xenical
Xenical: Up to 120 mg tds
• SGLT2 inhibitors
SGLT2 inhibitors: Empagliflozin up to 25mg daily, Canagliflozin up to 300mg daily
• DPP-4 Inhibitors
Sitagliptin up to 100 mg daily, Linagliptin up to 5mg daily

Locations

Country	Name	City	State
Singapore	Khoo Teck Puat Hospital	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
Khoo Teck Puat Hospital

Country where clinical trial is conducted

Singapore, 

References & Publications (8)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Blood Pressure measurement		12 months post randomisation
Secondary	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
Secondary	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