Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Effects of the Laparoscopic Roux-en-Y Gastric Bypass and Laparoscopic Mini Gastric Bypass on the Remission of Type II Diabetes Mellitus (DIABAR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03330756
Recruitment Status : Recruiting
First Posted : November 6, 2017
Last Update Posted : November 9, 2017
Sponsor:
Collaborator:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Information provided by (Responsible Party):
Slotervaart Hospital

Brief Summary:
It is estimated that there will be 439-552 million people with type 2 diabetes mellitus (T2DM) globally in 2030. Type 2 Diabetes Mellitus is present in one quarter of patients at the bariatric outpatient clinic. It is undecided which metabolic surgery grants best results in the remission of T2DM and which procedure does that at the lowest rate of surgical complications, long term difficulties and side effects. Non alcoholic fatty liver disease (NAFLD) is present in 80% of all morbidly obese subjects and is a major risk factor for development of insulin resistance and non alcoholic steatohepatis (NASH). It is increasingly recognized that the immune system, possibly driven by innate lymphoid cells (ILC's), and the intestinal microbiome are major players in this obesity related disease and the switch from benign to malign (insulin resistance and T2DM) obesity. However, the exact mechanisms of action behind the surgery-driven switch back from malign to benign obesity are unknown.Primary objective is to evaluate and compare the glycaemic control in T2DM within the first year of LRYGB and LMBG. Secondary aim is to gain insight in the pathophysiological mechanisms that drive the conversion of malign to benign obesity.

Condition or disease Intervention/treatment Phase
Obesity, Morbid Type 2 Diabetes Mellitus Procedure: laparoscopic Roux-en-Y gastric bypass Procedure: laparoscopic Mini gastric bypass Not Applicable

Detailed Description:
Metabolic surgery has proven to be a viable long-term solution in the treatment of morbid obesity and its comorbidities. It induces rapid remission of type 2 diabetes mellitus (T2DM). Type 2 Diabetes Mellitus is present in one quarter of patients at the bariatric outpatient clinic. Non alcoholic fatty liver disease (NAFLD) is present in 80% of all morbidly obese subjects and is a major risk factor for development of insulin resistance and non alcoholic steatohepatis (NASH), with the latter becoming the major indication for liver transplantation in the USA. It is increasingly recognized that the immune system, possibly driven by innate lymphoid cells (ILC's), and the intestinal microbiome are major players in this obesity related disease and the switch from benign to malign (insulin resistance and T2DM) obesity. However, the exact mechanisms of action behind the surgery-driven switch back from malign to benign obesity are unknown. Also, it is undecided which metabolic surgery grants best results in the remission of T2DM and which procedure does that at the lowest rate of surgical complications, long term difficulties and side effects. The Laparoscopic Roux-en-Y Gastric Bypass (LRYGB), an efficient but complex procedure, is the golden standard in the Netherlands. The Laparoscopic Mini Gastric Bypass (LMGB) is technically less challenging and has been introduced to overcome some of the limitations of LRYGB. It has been hypothesized that the LMGB has a more rapid and durable glycaemic control, possibly due to the altered constitution and the augmented length of the biliary limb. There is reason to believe that the improved glycaemic control might become apparent within the first year of surgery and that it might remain thereafter. However, it is unknown what order of magnitude is to be expected and whether subgroups of T2DM patients will benefit the LMGB more. Also, it is unknown whether and to what extent intestinal microbiota and immunological tone can predict the metabolic response (improvement in insulin sensitivity) and NAFLD/NASH reduction and whether differences are expected between these two surgeries. Increased understanding of the pathophysiological mechanisms as well as their relationship to metabolic disturbances are thought to be of crucial importance to discover new diagnostic and therapeutical targets in obesity associated insulin resistance/T2DM and NAFLD/NASH. Primary objective is to evaluate and compare the glycaemic control in T2DM within the first year of LRYGB and LMBG. Secondary aim is to gain insight in the pathophysiological mechanisms that drive the conversion of malign to benign obesity.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 220 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Single-center, open randomized controlled clinical trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Effects of the Laparoscopic Roux-en-Y Gastric Bypass and the Laparoscopic Mini Gastric Bypass on the Remission of Type II Diabetes Mellitus and the Pathophysiological Mechanisms That Drive the Conversion of Malign to Benign Obesity
Actual Study Start Date : October 23, 2017
Estimated Primary Completion Date : November 1, 2021
Estimated Study Completion Date : November 1, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Laparoscopic Roux-en-Y gastric bypass
Laparoscopic Roux-en-Y gastric bypass
Procedure: laparoscopic Roux-en-Y gastric bypass
laparoscopic Roux-en-Y gastric bypass with a 50 cm biliary limb and a 150 cm alimentary limb
Other Name: gastric bypass

Experimental: Laparoscopic Mini Gastric Bypass
laparoscopic Mini gastric bypass
Procedure: laparoscopic Mini gastric bypass
laparoscopic Mini gastric bypass with a gastrojejunostomy at 200 centimeters measured from the ligament of Treitz
Other Name: One anastomosis gastric bypass, omega loop gastric bypass




Primary Outcome Measures :
  1. glycaemic control [ Time Frame: 12 months FU ]
    as measured by the difference in HBa1C


Secondary Outcome Measures :
  1. glycaemic control [ Time Frame: 6 and 24 months FU ]
    as measured by the difference in HBa1C

  2. glycaemic control [ Time Frame: 6, 12 and 24 months FU ]
    as measured by the difference in HBa1C and anti-diabetic medication

  3. Insulin sensitivity [ Time Frame: baseline, 12, 24 months FU ]
    Mixed meal tolerance test for level of insulin sensitivity

  4. NAFLD/NASH [ Time Frame: day of surgery, reoperation ]
    NAFLD/NASH parameters in liver biopsy measured with the Steatosis, Activity and Fibrosis (SAF) score according to Bedossa et al (2012).For each patient a SAF score summarizing the main histological lesions will be defined. The steatosis score (S) will assess the quantities of larger or median-sized lipid droplets but not foamy microvesicules from 0 to 3 (S0 <5%; S1 5-33%; S2 34-66% and S3>67%). Activity grade (A) from 0-4 is the unweighted addition of hepatocyte ballooning (0-2) and lobular inflammation (0-2). Stage of fibrosis will be assessed using the score described by NASH-CRN as follows; stage 0 (F0) no fibrosis; stage 1 (F1) 1a or 1b perisinusoidal zone 3 or 1c portal fibrosis; stage 2 (F2) persinusoidal and periportal fibrosis without bridging; stage 3 (F3) bridging fibrosis and stage 4 (F4) cirrhosis. A diagnostic algorithm which will be used during this study can be found in the original paper published by Bedossa et al.

  5. Presence of bacterial DNA/bacterial metabolites - portal vein [ Time Frame: day of surgery, reoperation ]
    in portal vein blood

  6. Presence of bacterial DNA/bacterial metabolites - liver [ Time Frame: day of surgery, reoperation ]
    in liver

  7. Presence of bacterial DNA/bacterial metabolites - abdominal adipose tissue [ Time Frame: day of surgery, reoperation ]
    in abdominal adipose tissue depots

  8. Expression and differentiation of intestinal immunological cells - GALT [ Time Frame: day of surgery, reoperation ]
    in GALT

  9. Expression and differentiation of intestinal immunological cells - abdominal adipose tissue [ Time Frame: day of surgery, reoperation ]
    in abdominal adipose tissue depots

  10. Expression and differentiation of intestinal immunological cells - liver [ Time Frame: day of surgery, reoperation ]
    in liver

  11. Expression and differentiation of intestinal immunological cells - peripheral blood [ Time Frame: day of surgery, reoperation ]
    in peripheral blood

  12. Expression and differentiation of immunological cells [ Time Frame: 12 and 24 months FU ]
    ILC's, macrophages

  13. Expression and differentiation of inflammatory markers [ Time Frame: 12 and 24 months FU ]
    IL6, IRX3 and 5

  14. Small intestinal and fecal microbiota composition [ Time Frame: 2, and 6 weeks, 6 months, as well as 12 and 24 months after surgery ]
    feces

  15. Peripheral blood inflammatory markers [ Time Frame: 2, and 6 weeks, 6 months, as well as 12 and 24 months after surgery ]
    ILC's, macrophages, T/B-cells and dendritic cells

  16. Eating habits [ Time Frame: baseline, 12, 24 months FU ]
    G-food craving questionnaire (FCQ-T) 21 item questionaire scale 0 (never) - 6 (always)

  17. Eating habits [ Time Frame: baseline, 12, 24 months FU ]
    10 questions, scale 0-10 for instance 0 not hungry -10 very hungry / satiety / craving salty food / craving sweet food / craving fat food

  18. Excreted metabolites [ Time Frame: baseline, 12, 24 months FU ]
    urine

  19. Bio electric impedance [ Time Frame: baseline, 12, 24 months FU ]
    body composition as assesed by bioelectical impedance analysis (BIA): the measurement of body fat in relation to lean body mass.

  20. Quality of life [ Time Frame: baseline, 12, 24 months FU ]
    Quality of life (IWQOL lite) 5 domain questionaire, 31 items: 1 never true - 5 always true

  21. Cardiac / ventricular hypertrophy [ Time Frame: baseline, 12, 24 months FU ]
    Electrocardiogram (ECG)



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • BMI ≥35 and ≤50 kg/m2
  • Diagnosis and treatment of T2DM at intake at bariatric ward with use of anti-diabetic medication.
  • American Society of Anaesthesiologist Classification (ASA) ≤3
  • All patients are required to lose 6 kilograms of weight prior to surgery

Exclusion Criteria:

  • Known genetic basis for insulin resistance or glucose intolerance
  • Type 1 DM
  • Prior Bariatric surgery
  • Patients requiring a concomitant intervention (such as cholecystectomy, ventral hernia repair)
  • Auto-immune gastritis
  • Known presence of gastro-esophageal reflux disease
  • Known presence of large hiatal hernia requiring concomitant surgical repair
  • Coagulation disorders (PT time > 14 seconds, aPTT ((dependent on laboratory methods) or known presence of bleeding disorders (anamnestic))
  • Known presence of hemoglobinopathy
  • Uncontrolled hypertension (RR > 150/95 mmHg)
  • Renal insufficiency (creatinine > 150 umol/L)
  • Pregnancy
  • Breastfeeding
  • Alcohol or drug dependency
  • Primary lipid disorder
  • Participation in any other (therapeutic) study that may influence primary or secondary outcomes

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03330756


Contacts
Layout table for location contacts
Contact: Anne-Sophie van Rijswijk, MD +31205124460 anne-sophie.vanrijswijk@slz.nl
Contact: Maurits de Brauw, MD PhD maurits.debrauw@slz.nl

Locations
Layout table for location information
Netherlands
medical Center Slotervaart Recruiting
Amsterdam, Noord-Holland, Netherlands, 1066EC
Contact: Anne-Sophie van Rijswijk, MD    +31205014460    anne-sophie.vanrijswijk@slz.nl   
Contact: Maurtis de Brauw, MD PhD       maurits.debrauw@slz.nl   
Sponsors and Collaborators
Slotervaart Hospital
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Investigators
Layout table for investigator information
Principal Investigator: Maurits de Brauw, MD PhD Head of department of Surgery
Layout table for additonal information
Responsible Party: Slotervaart Hospital
ClinicalTrials.gov Identifier: NCT03330756    
Other Study ID Numbers: P1729
First Posted: November 6, 2017    Key Record Dates
Last Update Posted: November 9, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Slotervaart Hospital:
Roux-en-Y gastric bypass
Mini gastric bypass
Type 2 diabetes mellitus
Morbid Obesity
Additional relevant MeSH terms:
Layout table for MeSH terms
Diabetes Mellitus
Obesity
Diabetes Mellitus, Type 2
Obesity, Morbid
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight