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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Khoo Teck Puat Hospital
Sponsor:
Information provided by (Responsible Party):
Anton Cheng, Khoo Teck Puat Hospital
ClinicalTrials.gov Identifier:
NCT02041234
First received: January 10, 2014
Last updated: September 9, 2014
Last verified: September 2014
  Purpose

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 Intervention Phase
Type II Diabetes in the Not so Obese
Procedure: Roux-en-Y Gastric Bypass (RYGB)
Drug: Incretin analogues
Drug: Xenical
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Roux-en-Y Gastric Bypass for BMI 27-32 Type 2 Diabetes vs Best Medical Treatment

Resource links provided by NLM:


Further study details as provided by Khoo Teck Puat Hospital:

Primary Outcome Measures:
  • Number of subjects achieving HBA1c of 6% without diabetic medication [ Time Frame: at 12 month after randomisation ] [ Designated as safety issue: No ]
    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.

  • Number of subjects achieving systolic BP <130mm hg without antihypertension medication [ Time Frame: 12 months post randomisation ] [ Designated as safety issue: No ]
    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.

  • number of subjects achieving LDL level of <100mg/dl without lipid lowering medication [ Time Frame: 12 months post randomisation ] [ Designated as safety issue: No ]
    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:
  • fasting plasma glucose [ Time Frame: 12 months after Randomisation ] [ Designated as safety issue: No ]
    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.

  • Fasting Insulin [ Time Frame: 12 months after radomisation ] [ Designated as safety issue: No ]
    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.

  • serum c-peptide level [ Time Frame: 12 months post randomisation ] [ Designated as safety issue: No ]
    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.

  • serum lipid levels [ Time Frame: 12 months post randomisation ] [ Designated as safety issue: No ]
    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.

  • C-reactive protein level [ Time Frame: 12 months post randolmisation ] [ Designated as safety issue: No ]
    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.

  • change in medications usage [ Time Frame: 12 months post randomisation ] [ Designated as safety issue: No ]
    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.

  • changes in gut hormones levels [ Time Frame: 12 months post randomisation ] [ Designated as safety issue: No ]
    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.

  • changes in metabolic hormones level [ Time Frame: 12 months post randomisation ] [ Designated as safety issue: No ]
    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.

  • health resource utilisation [ Time Frame: 12 months post randomisation ] [ Designated as safety issue: No ]

    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.


  • HOMA-IR [ Time Frame: 12 months post randomisation ] [ Designated as safety issue: No ]
    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.

  • Blood Pressure measurement [ Time Frame: 12 months post randomisation ] [ Designated as safety issue: No ]
  • number of adverse events [ Time Frame: 12 months post randomisaiton ] [ Designated as safety issue: No ]
    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.

  • Weight loss [ Time Frame: 12 months post randomisation ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 20
Study Start Date: February 2014
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: Incretin analogues and Xenical
Incretin analogues: Liraglutide up to 1.8 mg daily. If unable to take incretin analogues: Januvia up to 100 mg daily. Xenical: Up to 120 mg tds. Participants will also take lipids & BP medications according to standard of care.
Drug: Incretin analogues
Incretin analogues: Liraglutide up to 1.8 mg daily If unable to take incretin analogues: Januvia up to 100 mg daily
Other Name: Liraglutide
Drug: Xenical
Xenical: Up to 120 mg tds

Detailed Description:

20 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.

  Eligibility

Ages Eligible for Study:   25 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Established diagnosis of DM2 = or < 5 years
  2. Age 25-65
  3. BMI 27-32.
  4. HBA1c = 8%, on insulin treatment.or starting on insulin/incretin analogs
  5. At least one of the following co-morbidities on treatment: hypertension, hyperlipidaemia, micro/macro-proteinuria or =class I nephropathy, retinopathy, ischaemic heart disease.

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 nM
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02041234

Contacts
Contact: Anton Cheng, MBBS 6602 3305 cheng.anton.ks@alexandrahealth.com.sg
Contact: Boon Khim Lim 6602 3307 lim.boon.khim@alexandrahealth.com.sg

Locations
Singapore
Khoo Teck Puat Hospital Recruiting
Singapore, Singapore, 768828
Contact: Bernice Tan    +65 6602 3305    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         
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:

Responsible Party: Anton Cheng, Dr Anton Cheng, Khoo Teck Puat Hospital
ClinicalTrials.gov Identifier: NCT02041234     History of Changes
Other Study ID Numbers: Bariatric Surgery RCT
Study First Received: January 10, 2014
Last Updated: September 9, 2014
Health Authority: Singapore: Health Sciences Authority
Singapore: Domain Specific Review Boards

Keywords provided by 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
Orlistat
Liraglutide
Incretins
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Obesity Agents
Central Nervous System Agents
Therapeutic Uses
Hypoglycemic Agents
Physiological Effects of Drugs
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on September 14, 2014