Obesity, Morbid
Conditions
Brief summary
Investigation of underlying metabolic mechanisms and impact on the two surgical procedures on inflammatory factors.
Detailed description
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).
Interventions
PROCEDURELong Biliopancreatic Limb LRYGB
LRYGB with an 180 cm biliopancreatic limb (BPL) and an alimentary limb (AL) of 80 cm.
PROCEDUREShort Biliopancreatic Limb LRYGB
Standard LRYGB with a 80 cm BPL and a 180 cm long AL.
Sponsors
University Hospital, Basel, Switzerland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in glucose tolerance | pre-OP and 6-8 months post-OP | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| glycemic control | pre-OP and 6-8 months post-OP | Change in glucose variability measured by continuous glucose measurement over 1 week, pre-OP and 6-8 months post-OP. |
| intestinal glucose absorption rate | pre-OP and 6-8 months post-OP | Differences in intestinal glucose absorption rate after ingestion of a standardized liquid test meal measured by 3-OMG |
| gastrointestinal peptides | pre-OP and 6-8 months post-OP | Differences in the release of gastrointestinal peptides after ingestion of a standardized liquid test meal |
| intestinal enteroendocrine cells | pre-OP and 6-8 months post-OP | Differences in number and phenotype (protein expression) of intestinal enteroendocrine cells (from ileum biopsies) |
| intestinal macrophages | pre-OP and 6-8 months post-OP | Differences in the number and phenotype (gene expression, methylation) of intestinal macrophages and subpopulations (from colon biopsies) |
| gut microbiota composition | pre-OP and 6-8 months post-OP | Differences in gut microbiota composition (from colon biopsy and fecal sample) |
| bile acids | pre-OP and 6-8 months post-OP | Differences in bile acids and metabolomic patterns (blood) |
| inflammatory profile | pre-OP and 6-8 months post-OP | Differences in inflammatory profile measured by hsCRP in blood |
| enterocyte gene expression | pre-OP and 6-8 months post-OP | Differences in enterocyte gene expression or DNA-methylation (tissue samples from ileum biopsies) |
| appetite-related sensations | pre-OP and 6-8 months post-OP | Differences in subjective appetite-related sensations (feelings of hunger, prospective food consumption, satiation and fullness) after liquid test meal, assessed with Visual Analog Scales |
| body composition | pre-OP and 6-8 months post-OP | Body composition (measured by Bio Impedance Analysis (BIA)) |
| mineral metabolism (blood) 1 | pre-OP and 6-8 months post-OP | Differences in mineral metabolism parameter (creatinine) in blood samples. |
| mineral metabolism (blood) 2 | pre-OP and 6-8 months post-OP | Differences in mineral metabolism parameter (phosphate) in blood samples. |
| mineral metabolism (blood) 3 | pre-OP and 6-8 months post-OP | Differences in mineral metabolism parameter (calcium) in blood samples. |
| mineral metabolism (blood) 4 | pre-OP and 6-8 months post-OP | Differences in mineral metabolism parameter (magnesium) in blood samples. |
| mineral metabolism (blood) 5 | pre-OP and 6-8 months post-OP | Differences in mineral metabolism parameter (parathyroid hormone) in blood samples. |
| mineral metabolism (blood) 6 | pre-OP and 6-8 months post-OP | Differences in mineral metabolism parameter (calcidiol) in blood samples. |
| mineral metabolism (blood) 7 | pre-OP and 6-8 months post-OP | Differences in mineral metabolism parameter (calcitriol) in blood samples. |
| mineral metabolism (blood) 8 | pre-OP and 6-8 months post-OP | Differences in mineral metabolism parameter (FGF23) in blood samples. |
| mineral metabolism (blood) 9 | pre-OP and 6-8 months post-OP | Differences in mineral metabolism parameter (desoxypyridinoline) in blood samples. |
| mineral metabolism (blood) 10 | pre-OP and 6-8 months post-OP | Differences in mineral metabolism parameter (bone alkaline phosphatase (bALP)) in blood samples. |
| mineral metabolism (blood) 11 | pre-OP and 6-8 months post-OP | Differences in mineral metabolism parameter (osteocalcin) in blood samples. |
| mineral metabolism (blood) 12 | pre-OP and 6-8 months post-OP | Differences in mineral metabolism parameter (sclerostin) in blood samples. |
| mineral metabolism (blood) 13 | pre-OP and 6-8 months post-OP | Differences in mineral metabolism parameter (P1NP) in blood samples. |
| mineral metabolism (blood) 14 | pre-OP and 6-8 months post-OP | Differences in mineral metabolism parameter (CTX) in blood samples. |
| mineral metabolism (stool) 1 | pre-OP and 6-8 months post-OP | Differences in mineral metabolism parameter (phosphate) in feces samples. |
| mineral metabolism (stool) 2 | pre-OP and 6-8 months post-OP | Differences in mineral metabolism parameter (calcium) in feces samples. |
| mineral metabolism (stool) 3 | pre-OP and 6-8 months post-OP | Differences in mineral metabolism parameter (magnesium) in feces samples. |
| mineral metabolism (urine) 1 | pre-OP and 6-8 months post-OP | Differences in mineral metabolism parameter (creatinine) in urine samples. |
| mineral metabolism (urine) 2 | pre-OP and 6-8 months post-OP | Differences in mineral metabolism parameter (phosphate) in urine samples. |
| mineral metabolism (urine) 3 | pre-OP and 6-8 months post-OP | Differences in mineral metabolism parameter (calcium) in urine samples. |
| mineral metabolism (urine) 4 | pre-OP and 6-8 months post-OP | Differences in mineral metabolism parameter (magnesium) in urine samples. |
| mineral metabolism (urine) 5 | pre-OP and 6-8 months post-OP | Differences in mineral metabolism parameter (desoxypyridinoline) in urine samples. |
| metabolomic patterns | pre-OP and 6-8 months post-OP | Differences in metabolomic patterns assed in blood sample, urine sample, stool sample and exhaled breath. |
| immune response | pre-OP and 6-8 months post-OP | Differences in immune response biomarkers in blood measured by a cytokine screening assay |
Countries
Switzerland
Contacts
PRINCIPAL_INVESTIGATORAnne Christin Meyer-Gerspach, PD Dr. phil. II Dr. habil.
St. Clara Forschung AG / St. Claraspital AG
PRINCIPAL_INVESTIGATORBettina Wölnerhanssen, PD Dr. med.
St. Clara Forschung AG / St. Claraspital AG
Outcome results
None listed