Clinical trial NCT00999050: Laparoscopic Gastric Bypass for Type 2 Diabetes Mellitus With Body Mass Index (BMI) < 35
Official title: Laparoscopic Gastric Bypass for Type 2 Diabetes Mellitus: a Pilot Prospective Study in Overweight and Mildly Obese Subjects
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Keywords: type two diabetes
gastric bypass surgery
overweight or moderately obese
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
First posted: 2009-10-21
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The aim of this study is to evaluate the effect of Roux-en-y gastric bypass (RYGB) in controlling diabetes in subjects with mild obesity (BMI 26-35). The primary endpoint will be the reduction of HbA1c (\< 7%), a standard measure of diabetes control; the secondary endpoints will be changes blood sugar , vitamin levels, insulin, c-peptide, and lipids levels, as well as retinal eye examinations, urinalysis to assess kidney function, carotid ultrasound as a marker of cardiovascular function, and alterations in diabetic medications. Fifty subjects with medically documented type 2 Diabetes Mellitus (T2DM) with BMIs between 26 and 35 will undergo standard laparoscopic RYGB. Prior and after surgery, the subjects will undergo a clinical evaluation in regard to the primary and secondary endpoints listed. The pre-surgery evaluation is directed toward establishing the existence of diabetes related complications prior to surgery. After surgery subjects will be closely monitored for complications and required changes in their diabetes management. Repeat assessments will be made at 1, 3, 6, and 12 months and at two years.

Detailed description: The primary endpoint will be the reduction of HbA1c and secondary endpoints will be multiple associated parameters as listed below. A group of 50 subjects with medically documented T2DM and BMI of 26-35 will undergo standard laparoscopic RYGB. Prior to surgery, the subjects will undergo the standard pre-operative work up required for conventional bariatric surgery. This includes full history and physical exam, medical/cardiac clearances as needed, nutrition consultation and a gastrointestinal consultation for upper endoscopy. After thorough explanation an approved informed consent will be signed. Baseline parameters, as listed below, will be measured for each subject to identify possible complications of diabetes prior to the surgical intervention..

After surgery perioperative complications will be monitored and required modifications of diabetes management advised. Followed up measurements at 1, 3, 6, 12, and 24 months is consistent with standard clinical practice guidelines. Data analysis will be ongoing to observe the effects of the surgical intervention on glucose homeostasis.

* Baseline parameters
* History and Physical Exam
* Weight/BMI/ body composition with the Tanita 310.
* Waist Circumference
* Blood Pressure
* CBC
* HbA1c
* Fasting glucose
* Vitamin B6, B12, Folate,and Iron status
* Lipid Profile -total cholesterol, HDL, LDL, triglyceride
* Fasting Insulin and C-peptide
* Stimulated C-peptide
* EKG
* Retinal exam
* Urinalysis (assess for proteinuria and microalbuminuria)
* Comprehensive foot exam
* Medications and dosage
* Quality of Life Score (SF-36)
* Carotid ultrasound (intima-media thickness)

Follow-up:

4 Weeks:

* Physical Examination, wound check, Body weight, BMI,
* Glucose Diary (pre and postprandial glucose levels as required)
* Insulin and C-peptide
* Lipid profile
* Medication use

  3 Months, 6 months,

Same as above plus:

* HbA1c
* Vitamin levels and iron status
* Retinal exam
* Annually the baseline measurements will be repeated

Eligibility criteria: Inclusion Criteria:

Adult males and females who meet the following inclusion criteria will be offered the opportunity to participate in the study:

1. Diagnosis of type 2 Diabetes Mellitus (T2DM) confirmed by the following criteria:

   1. normal or high C-peptide level (\> 0.9 ng/ml) to exclude type 1 Diabetes Mellitus
   2. positive glucagon test to confirm T2DM
   3. fasting plasma glucose of 126 mg/dl or more on at least two occasions
2. Body mass index (BMI) 26 kg/m2 or greater, and less than 35 kg/m2
3. History of T2DM for not longer than 8 years, as long-standing disease beyond 8 years correlates with failure to achieve diabetes resolution after gastric bypass
4. No contraindication for surgery or general anesthesia as determined by a multidisciplinary bariatric surgery team (surgeon, anesthesiologist, internist, dietitian, psychologist)
5. Between 18 and 65 year of age
6. Able to provide informed consent
7. If a female with reproductive potential, she has to agree to use a reliable method of birth control for at least one year from the date of surgery

Exclusion Criteria

Subjects who meet any of the following exclusion criteria will not be eligible to participate in the study:

1. Enrollment in another clinical study, which involves an investigational drug
2. Diagnosis of type 1 Diabetes Mellitus or other genetic forms of Diabetes Mellitus
3. Significant renal failure of chronic liver disease (except NAFLD)
4. Major psychological disorders
5. Pregnancy - all female subjects will have serum beta-hCG prior to operation, and must use birth control of their choice to avoid pregnancy during the first year after surgery
6. Previous gastric or esophageal surgery
7. Immunosuppressive drugs including corticosteroids
8. Coagulopathy defined as an INR \> 1.5 or platelet count \< 50,000/µl
9. Anemia defined as a Hb \<10.0 g/dl
10. Inflammatory bowel diseases or other medical condition that would serve as a contraindication to gastric bypass (eg. celiac sprue, pancreatic insufficiency)
11. A severe concurrent illness that is likely to limit life or require extensive systemic treatment (e.g. cancer)
12. A pre-existing major complication of diabetes:

    1. unstable, proliferative retinopathy
    2. severe autonomic cardiac neuropathy or intestinal neuropathy
    3. Myocardial infarction within the previous year, current unstable angina, or poorly-controlled congestive heart failure (Stage III)

Primary outcomes:
measure: Hemoglobin A1C changes
timeFrame: Post gastric bypass operation
Secondary outcomes:
measure: improvement in glycemic control
timeFrame: 1 to two years
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medical College New York Prysbyterian Hosptial
state: New York
Study officials:
References:
citation: Cohen R, Pinheiro JS, Correa JL, Schiavon CA. Laparoscopic Roux-en-Y gastric bypass for BMI < 35 kg/m(2): a tailored approach. Surg Obes Relat Dis. 2006; 2(3):401-4. Cohen RV, Schiavon CA, Pinheiro JS, Correa JL, Rubino F. Duodenal-jejunal bypass for the treatment of type 2 diabetes in patients with body mass index of 22-34 kg/m2: a report of 2 cases. Surg Obes Relat Dis. 2007; 3(2): 195-7. Lee WJ, Wang W, Lee YC, Huang MT, Ser KH, Chen JC. Effect of laparoscopic mini-gastric bypass for type 2 diabetes mellitus: comparison of BMI>35 and <35 kg/m2. J Gastrointest Surg. 2008; 12(5): 945-52. Scopinaro N, Papadia F, Marinari G, Camerini G, Adami G. Long-term control of type 2 diabetes mellitus and the other major components of the metabolic syndrome after biliopancreatic diversion in patients with BMI < 35 kg/m2. Obes Surg. 2007; 17(2): 185-92. Chiellini C, Rubino F, Castagneto M, Nanni G, Mingrone G. The effect of bilio-pancreatic diversion on type 2 diabetes in patients with BMI <35 kg/m2. Diabetologia. 2009; 52(6): 1027-30.