Different Limb Lengths in Gastric Bypass Surgery (SLIM) - Part 3: Metabolism and Inflammation

Study Overview
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Brief Summary
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Investigation of underlying metabolic mechanisms and impact on the two surgical procedures on inflammatory factors.

Detailed Description
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The aim of this project is to investigate underlying metabolic mechanisms in a subpopulation of patients of the SLIM trial, where a laparoscopic proximal Roux-en-Y gastric bypass (LRYGB) with a longer biliopancreatic limb (BPL) is compared to a standard LRYGB. For this purpose, the aim is to examine differences in number of intestinal enteroendocrine cells, subpopulations of intestinal macrophages, and gene expression or DNA-methylation in tissue samples obtained by colonoscopy from the ileum and transverse colon. In addition, gut microbiota (from colon biopsy and fecal samples), meal-stimulated gut hormone profiles, glycemic control, and metabolite patterns (metabolomics; in blood, urine, stool and breath) including plasma bile acid concentrations preoperatively and 6 months post-surgery will be examined. Body composition (fat mass and lean mass) will be measured by means of BIA (bioimpedance analysis; Biacorpus).

Official Title
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Swiss Multicenter Randomized Controlled Trial on Different Limb Lengths in Gastric Bypass Surgery (SLIM Trial) - Part 3: Metabolic Mechanisms and Inflammatory Response

Conditions
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Obesity, Morbid

Intervention / Treatment
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* Procedure: Long Biliopancreatic Limb LRYGB
* Procedure: Short Biliopancreatic Limb LRYGB


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 2 x 25 patients with morbid obestiy (BMI of 35 kg/m2 or higher) who comply with the regulatory rules for bariatric surgery in Switzerland (SMOB guidelines) and participate in the SLIM Trial 15 healthy lean controls Exclusion Criteria: general contraindications to kind of surgery known or suspected non-compliance inability to follow the procedures of the study, e.g. due to language problems, psychological disorders etc. of the participant participation in another interventional study BMI > 60 kg/m2 height < 145 cm CL length of < 180 cm as measured intraoperatively ASA physical status classification > III inflammatory bowel disease diabetes intake of corticosteroids, anti-inflammatory/ immunosuppressive drugs potentially altering immune cells clinical signs of current infection known anemia (e.g. hemoglobin < 110g/L for males, < 100g/L for females) known neutropenia (e.g. leucocyte count < 1.5 x 10^9/L or ANC < 0.5 x 10^9/L) known immunodeficiency, e.g. HIV known vasculitis, collagenosis known adrenal insufficiency and/or substitution with glucocorticoids risky daily alcohol consumption (> 24g/d for males, > 12g/d for females) drug abuse known liver cirrhosis Child B or C known uncontrolled congestive heart failure known uncontrolled malignant disease currently pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Long Biliopancreatic Limb LRYGB<br>25 morbidly obese patients undergoing gastric bypass surgery, participating in SLIM Trial. | Procedure: Long Biliopancreatic Limb LRYGB<br>* LRYGB with an 180 cm biliopancreatic limb (BPL) and an alimentary limb (AL) of 80 cm.<br>|
| Active Comparator: Short Biliopancreatic Limb LRYGB<br>25 morbidly obese patients undergoing gastric bypass surgery, participating in SLIM Trial. | Procedure: Short Biliopancreatic Limb LRYGB<br>* Standard LRYGB with a 80 cm BPL and a 180 cm long AL.<br>|
| No Intervention: Control<br>15 normal weight control group without surgery. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in glucose tolerance | Change in glucose tolerance as measured by plasma glucose concentrations at 120 minutes after ingestion of a standardized liquid test meal, pre-OP and 6-8 months post-OP. | pre-OP and 6-8 months post-OP | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| glycemic control | Change in glucose variability measured by continuous glucose measurement over 1 week, pre-OP and 6-8 months post-OP. | pre-OP and 6-8 months post-OP | 
| intestinal glucose absorption rate | Differences in intestinal glucose absorption rate after ingestion of a standardized liquid test meal measured by 3-OMG | pre-OP and 6-8 months post-OP | 
| gastrointestinal peptides | Differences in the release of gastrointestinal peptides after ingestion of a standardized liquid test meal | pre-OP and 6-8 months post-OP | 
| intestinal enteroendocrine cells | Differences in number and phenotype (protein expression) of intestinal enteroendocrine cells (from ileum biopsies) | pre-OP and 6-8 months post-OP | 
| intestinal macrophages | Differences in the number and phenotype (gene expression, methylation) of intestinal macrophages and subpopulations (from colon biopsies) | pre-OP and 6-8 months post-OP | 
| gut microbiota composition | Differences in gut microbiota composition (from colon biopsy and fecal sample) | pre-OP and 6-8 months post-OP | 
| bile acids | Differences in bile acids and metabolomic patterns (blood) | pre-OP and 6-8 months post-OP | 
| inflammatory profile | Differences in inflammatory profile measured by hsCRP in blood | pre-OP and 6-8 months post-OP | 
| enterocyte gene expression | Differences in enterocyte gene expression or DNA-methylation (tissue samples from ileum biopsies) | pre-OP and 6-8 months post-OP | 
| appetite-related sensations | Differences in subjective appetite-related sensations (feelings of hunger, prospective food consumption, satiation and fullness) after liquid test meal, assessed with Visual Analog Scales | pre-OP and 6-8 months post-OP | 
| body composition | Body composition (measured by Bio Impedance Analysis (BIA)) | pre-OP and 6-8 months post-OP | 
| mineral metabolism (blood) 1 | Differences in mineral metabolism parameter (creatinine) in blood samples. | pre-OP and 6-8 months post-OP | 
| mineral metabolism (blood) 2 | Differences in mineral metabolism parameter (phosphate) in blood samples. | pre-OP and 6-8 months post-OP | 
| mineral metabolism (blood) 3 | Differences in mineral metabolism parameter (calcium) in blood samples. | pre-OP and 6-8 months post-OP | 
| mineral metabolism (blood) 4 | Differences in mineral metabolism parameter (magnesium) in blood samples. | pre-OP and 6-8 months post-OP | 
| mineral metabolism (blood) 5 | Differences in mineral metabolism parameter (parathyroid hormone) in blood samples. | pre-OP and 6-8 months post-OP | 
| mineral metabolism (blood) 6 | Differences in mineral metabolism parameter (calcidiol) in blood samples. | pre-OP and 6-8 months post-OP | 
| mineral metabolism (blood) 7 | Differences in mineral metabolism parameter (calcitriol) in blood samples. | pre-OP and 6-8 months post-OP | 
| mineral metabolism (blood) 8 | Differences in mineral metabolism parameter (FGF23) in blood samples. | pre-OP and 6-8 months post-OP | 
| mineral metabolism (blood) 9 | Differences in mineral metabolism parameter (desoxypyridinoline) in blood samples. | pre-OP and 6-8 months post-OP | 
| mineral metabolism (blood) 10 | Differences in mineral metabolism parameter (bone alkaline phosphatase (bALP)) in blood samples. | pre-OP and 6-8 months post-OP | 
| mineral metabolism (blood) 11 | Differences in mineral metabolism parameter (osteocalcin) in blood samples. | pre-OP and 6-8 months post-OP | 
| mineral metabolism (blood) 12 | Differences in mineral metabolism parameter (sclerostin) in blood samples. | pre-OP and 6-8 months post-OP | 
| mineral metabolism (blood) 13 | Differences in mineral metabolism parameter (P1NP) in blood samples. | pre-OP and 6-8 months post-OP | 
| mineral metabolism (blood) 14 | Differences in mineral metabolism parameter (CTX) in blood samples. | pre-OP and 6-8 months post-OP | 
| mineral metabolism (stool) 1 | Differences in mineral metabolism parameter (phosphate) in feces samples. | pre-OP and 6-8 months post-OP | 
| mineral metabolism (stool) 2 | Differences in mineral metabolism parameter (calcium) in feces samples. | pre-OP and 6-8 months post-OP | 
| mineral metabolism (stool) 3 | Differences in mineral metabolism parameter (magnesium) in feces samples. | pre-OP and 6-8 months post-OP | 
| mineral metabolism (urine) 1 | Differences in mineral metabolism parameter (creatinine) in urine samples. | pre-OP and 6-8 months post-OP | 
| mineral metabolism (urine) 2 | Differences in mineral metabolism parameter (phosphate) in urine samples. | pre-OP and 6-8 months post-OP | 
| mineral metabolism (urine) 3 | Differences in mineral metabolism parameter (calcium) in urine samples. | pre-OP and 6-8 months post-OP | 
| mineral metabolism (urine) 4 | Differences in mineral metabolism parameter (magnesium) in urine samples. | pre-OP and 6-8 months post-OP | 
| mineral metabolism (urine) 5 | Differences in mineral metabolism parameter (desoxypyridinoline) in urine samples. | pre-OP and 6-8 months post-OP | 
| metabolomic patterns | Differences in metabolomic patterns assed in blood sample, urine sample, stool sample and exhaled breath. | pre-OP and 6-8 months post-OP | 
| immune response | Differences in immune response biomarkers in blood measured by a cytokine screening assay | pre-OP and 6-8 months post-OP |