Clinical trial NCT03330756: The Effects of the Laparoscopic Roux-en-Y Gastric Bypass and Laparoscopic Mini Gastric Bypass on the Remission of Type II Diabetes Mellitus
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Obesity, Morbid
Type 2 Diabetes Mellitus
Keywords: Roux-en-Y gastric bypass
Mini gastric bypass
Type 2 diabetes mellitus
Morbid Obesity
Lead sponsor: Slotervaart Hospital
Sponsor class: OTHER
Collaborators: name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
First posted: 2017-11-06
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single-center, open randomized controlled clinical trial
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: glycaemic control
timeFrame: 12 months FU
Secondary outcomes:
measure: glycaemic control
timeFrame: 6 and 24 months FU
measure: glycaemic control
timeFrame: 6, 12 and 24 months FU
measure: Insulin sensitivity
timeFrame: baseline, 12, 24 months FU
measure: NAFLD/NASH
timeFrame: day of surgery, reoperation
measure: Presence of bacterial DNA/bacterial metabolites - portal vein
timeFrame: day of surgery, reoperation
measure: Presence of bacterial DNA/bacterial metabolites - liver
timeFrame: day of surgery, reoperation
measure: Presence of bacterial DNA/bacterial metabolites - abdominal adipose tissue
timeFrame: day of surgery, reoperation
measure: Expression and differentiation of intestinal immunological cells - GALT
timeFrame: day of surgery, reoperation
measure: Expression and differentiation of intestinal immunological cells - abdominal adipose tissue
timeFrame: day of surgery, reoperation
measure: Expression and differentiation of intestinal immunological cells - liver
timeFrame: day of surgery, reoperation
measure: Expression and differentiation of intestinal immunological cells - peripheral blood
timeFrame: day of surgery, reoperation
measure: Expression and differentiation of immunological cells
timeFrame: 12 and 24 months FU
measure: Expression and differentiation of inflammatory markers
timeFrame: 12 and 24 months FU
measure: Small intestinal and fecal microbiota composition
timeFrame: 2, and 6 weeks, 6 months, as well as 12 and 24 months after surgery
measure: Peripheral blood inflammatory markers
timeFrame: 2, and 6 weeks, 6 months, as well as 12 and 24 months after surgery
measure: Eating habits
timeFrame: baseline, 12, 24 months FU
measure: Eating habits
timeFrame: baseline, 12, 24 months FU
measure: Excreted metabolites
timeFrame: baseline, 12, 24 months FU
measure: Bio electric impedance
timeFrame: baseline, 12, 24 months FU
measure: Quality of life
timeFrame: baseline, 12, 24 months FU
measure: Cardiac / ventricular hypertrophy
timeFrame: baseline, 12, 24 months FU
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: medical Center Slotervaart
state: Noord-Holland
Study officials:
affiliation: Head of department of Surgery
name: Maurits de Brauw, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: van Rijswijk A, van Olst N, Meijnikman AS, Acherman YIZ, Bruin SC, van de Laar AW, van Olden CC, Aydin O, Borger H, Beuers UHW, Herrema H, Verheij J, Apers JA, Backhed F, Gerdes VEA, Nieuwdorp M, de Brauw LM. The effects of laparoscopic Roux-en-Y gastric bypass and one-anastomosis gastric bypass on glycemic control and remission of type 2 diabetes mellitus: study protocol for a multi-center randomized controlled trial (the DIABAR-trial). Trials. 2022 Oct 22;23(1):900. doi: 10.1186/s13063-022-06762-3.