Different Limb Lengths in Gastric Bypass Surgery (SLIM) - Part 3: Metabolism and Inflammation (SLIM - Part 3)
Primary Purpose
Obesity, Morbid
Status
Recruiting
Phase
Not Applicable
Locations
Switzerland
Study Type
Interventional
Intervention
Long Biliopancreatic Limb LRYGB
Short Biliopancreatic Limb LRYGB
Sponsored by
About this trial
This is an interventional basic science trial for Obesity, Morbid
Eligibility Criteria
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
Sites / Locations
- St Clara Research Ltd, St Claraspital BaselRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
No Intervention
Arm Label
Long Biliopancreatic Limb LRYGB
Short Biliopancreatic Limb LRYGB
Control
Arm Description
25 morbidly obese patients undergoing gastric bypass surgery, participating in SLIM Trial.
25 morbidly obese patients undergoing gastric bypass surgery, participating in SLIM Trial.
15 normal weight control group without surgery.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
glycemic control
Change in glucose variability measured by continuous glucose measurement over 1 week, 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
gastrointestinal peptides
Differences in the release of gastrointestinal peptides after ingestion of a standardized liquid test meal
intestinal enteroendocrine cells
Differences in number and phenotype (protein expression) of intestinal enteroendocrine cells (from ileum biopsies)
intestinal macrophages
Differences in the number and phenotype (gene expression, methylation) of intestinal macrophages and subpopulations (from colon biopsies)
gut microbiota composition
Differences in gut microbiota composition (from colon biopsy and fecal sample)
bile acids
Differences in bile acids and metabolomic patterns (blood)
inflammatory profile
Differences in inflammatory profile measured by hsCRP in blood
enterocyte gene expression
Differences in enterocyte gene expression or DNA-methylation (tissue samples from ileum biopsies)
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
body composition
Body composition (measured by Bio Impedance Analysis (BIA))
mineral metabolism (blood) 1
Differences in mineral metabolism parameter (creatinine) in blood samples.
mineral metabolism (blood) 2
Differences in mineral metabolism parameter (phosphate) in blood samples.
mineral metabolism (blood) 3
Differences in mineral metabolism parameter (calcium) in blood samples.
mineral metabolism (blood) 4
Differences in mineral metabolism parameter (magnesium) in blood samples.
mineral metabolism (blood) 5
Differences in mineral metabolism parameter (parathyroid hormone) in blood samples.
mineral metabolism (blood) 6
Differences in mineral metabolism parameter (calcidiol) in blood samples.
mineral metabolism (blood) 7
Differences in mineral metabolism parameter (calcitriol) in blood samples.
mineral metabolism (blood) 8
Differences in mineral metabolism parameter (FGF23) in blood samples.
mineral metabolism (blood) 9
Differences in mineral metabolism parameter (desoxypyridinoline) in blood samples.
mineral metabolism (blood) 10
Differences in mineral metabolism parameter (bone alkaline phosphatase (bALP)) in blood samples.
mineral metabolism (blood) 11
Differences in mineral metabolism parameter (osteocalcin) in blood samples.
mineral metabolism (blood) 12
Differences in mineral metabolism parameter (sclerostin) in blood samples.
mineral metabolism (blood) 13
Differences in mineral metabolism parameter (P1NP) in blood samples.
mineral metabolism (blood) 14
Differences in mineral metabolism parameter (CTX) in blood samples.
mineral metabolism (stool) 1
Differences in mineral metabolism parameter (phosphate) in feces samples.
mineral metabolism (stool) 2
Differences in mineral metabolism parameter (calcium) in feces samples.
mineral metabolism (stool) 3
Differences in mineral metabolism parameter (magnesium) in feces samples.
mineral metabolism (urine) 1
Differences in mineral metabolism parameter (creatinine) in urine samples.
mineral metabolism (urine) 2
Differences in mineral metabolism parameter (phosphate) in urine samples.
mineral metabolism (urine) 3
Differences in mineral metabolism parameter (calcium) in urine samples.
mineral metabolism (urine) 4
Differences in mineral metabolism parameter (magnesium) in urine samples.
mineral metabolism (urine) 5
Differences in mineral metabolism parameter (desoxypyridinoline) in urine samples.
metabolomic patterns
Differences in metabolomic patterns assed in blood sample, urine sample, stool sample and exhaled breath.
immune response
Differences in immune response biomarkers in blood measured by a cytokine screening assay
Full Information
NCT ID
NCT05471037
First Posted
March 21, 2022
Last Updated
August 15, 2022
Sponsor
University Hospital, Basel, Switzerland
1. Study Identification
Unique Protocol Identification Number
NCT05471037
Brief Title
Different Limb Lengths in Gastric Bypass Surgery (SLIM) - Part 3: Metabolism and Inflammation
Acronym
SLIM - Part 3
Official Title
Swiss Multicenter Randomized Controlled Trial on Different Limb Lengths in Gastric Bypass Surgery (SLIM Trial) - Part 3: Metabolic Mechanisms and Inflammatory Response
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 1, 2022 (Actual)
Primary Completion Date
January 1, 2025 (Anticipated)
Study Completion Date
January 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Basel, Switzerland
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Morbid
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
65 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Long Biliopancreatic Limb LRYGB
Arm Type
Active Comparator
Arm Description
25 morbidly obese patients undergoing gastric bypass surgery, participating in SLIM Trial.
Arm Title
Short Biliopancreatic Limb LRYGB
Arm Type
Active Comparator
Arm Description
25 morbidly obese patients undergoing gastric bypass surgery, participating in SLIM Trial.
Arm Title
Control
Arm Type
No Intervention
Arm Description
15 normal weight control group without surgery.
Intervention Type
Procedure
Intervention Name(s)
Long Biliopancreatic Limb LRYGB
Intervention Description
LRYGB with an 180 cm biliopancreatic limb (BPL) and an alimentary limb (AL) of 80 cm.
Intervention Type
Procedure
Intervention Name(s)
Short Biliopancreatic Limb LRYGB
Intervention Description
Standard LRYGB with a 80 cm BPL and a 180 cm long AL.
Primary Outcome Measure Information:
Title
Change in glucose tolerance
Description
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.
Time Frame
pre-OP and 6-8 months post-OP
Secondary Outcome Measure Information:
Title
glycemic control
Description
Change in glucose variability measured by continuous glucose measurement over 1 week, pre-OP and 6-8 months post-OP.
Time Frame
pre-OP and 6-8 months post-OP
Title
intestinal glucose absorption rate
Description
Differences in intestinal glucose absorption rate after ingestion of a standardized liquid test meal measured by 3-OMG
Time Frame
pre-OP and 6-8 months post-OP
Title
gastrointestinal peptides
Description
Differences in the release of gastrointestinal peptides after ingestion of a standardized liquid test meal
Time Frame
pre-OP and 6-8 months post-OP
Title
intestinal enteroendocrine cells
Description
Differences in number and phenotype (protein expression) of intestinal enteroendocrine cells (from ileum biopsies)
Time Frame
pre-OP and 6-8 months post-OP
Title
intestinal macrophages
Description
Differences in the number and phenotype (gene expression, methylation) of intestinal macrophages and subpopulations (from colon biopsies)
Time Frame
pre-OP and 6-8 months post-OP
Title
gut microbiota composition
Description
Differences in gut microbiota composition (from colon biopsy and fecal sample)
Time Frame
pre-OP and 6-8 months post-OP
Title
bile acids
Description
Differences in bile acids and metabolomic patterns (blood)
Time Frame
pre-OP and 6-8 months post-OP
Title
inflammatory profile
Description
Differences in inflammatory profile measured by hsCRP in blood
Time Frame
pre-OP and 6-8 months post-OP
Title
enterocyte gene expression
Description
Differences in enterocyte gene expression or DNA-methylation (tissue samples from ileum biopsies)
Time Frame
pre-OP and 6-8 months post-OP
Title
appetite-related sensations
Description
Differences in subjective appetite-related sensations (feelings of hunger, prospective food consumption, satiation and fullness) after liquid test meal, assessed with Visual Analog Scales
Time Frame
pre-OP and 6-8 months post-OP
Title
body composition
Description
Body composition (measured by Bio Impedance Analysis (BIA))
Time Frame
pre-OP and 6-8 months post-OP
Title
mineral metabolism (blood) 1
Description
Differences in mineral metabolism parameter (creatinine) in blood samples.
Time Frame
pre-OP and 6-8 months post-OP
Title
mineral metabolism (blood) 2
Description
Differences in mineral metabolism parameter (phosphate) in blood samples.
Time Frame
pre-OP and 6-8 months post-OP
Title
mineral metabolism (blood) 3
Description
Differences in mineral metabolism parameter (calcium) in blood samples.
Time Frame
pre-OP and 6-8 months post-OP
Title
mineral metabolism (blood) 4
Description
Differences in mineral metabolism parameter (magnesium) in blood samples.
Time Frame
pre-OP and 6-8 months post-OP
Title
mineral metabolism (blood) 5
Description
Differences in mineral metabolism parameter (parathyroid hormone) in blood samples.
Time Frame
pre-OP and 6-8 months post-OP
Title
mineral metabolism (blood) 6
Description
Differences in mineral metabolism parameter (calcidiol) in blood samples.
Time Frame
pre-OP and 6-8 months post-OP
Title
mineral metabolism (blood) 7
Description
Differences in mineral metabolism parameter (calcitriol) in blood samples.
Time Frame
pre-OP and 6-8 months post-OP
Title
mineral metabolism (blood) 8
Description
Differences in mineral metabolism parameter (FGF23) in blood samples.
Time Frame
pre-OP and 6-8 months post-OP
Title
mineral metabolism (blood) 9
Description
Differences in mineral metabolism parameter (desoxypyridinoline) in blood samples.
Time Frame
pre-OP and 6-8 months post-OP
Title
mineral metabolism (blood) 10
Description
Differences in mineral metabolism parameter (bone alkaline phosphatase (bALP)) in blood samples.
Time Frame
pre-OP and 6-8 months post-OP
Title
mineral metabolism (blood) 11
Description
Differences in mineral metabolism parameter (osteocalcin) in blood samples.
Time Frame
pre-OP and 6-8 months post-OP
Title
mineral metabolism (blood) 12
Description
Differences in mineral metabolism parameter (sclerostin) in blood samples.
Time Frame
pre-OP and 6-8 months post-OP
Title
mineral metabolism (blood) 13
Description
Differences in mineral metabolism parameter (P1NP) in blood samples.
Time Frame
pre-OP and 6-8 months post-OP
Title
mineral metabolism (blood) 14
Description
Differences in mineral metabolism parameter (CTX) in blood samples.
Time Frame
pre-OP and 6-8 months post-OP
Title
mineral metabolism (stool) 1
Description
Differences in mineral metabolism parameter (phosphate) in feces samples.
Time Frame
pre-OP and 6-8 months post-OP
Title
mineral metabolism (stool) 2
Description
Differences in mineral metabolism parameter (calcium) in feces samples.
Time Frame
pre-OP and 6-8 months post-OP
Title
mineral metabolism (stool) 3
Description
Differences in mineral metabolism parameter (magnesium) in feces samples.
Time Frame
pre-OP and 6-8 months post-OP
Title
mineral metabolism (urine) 1
Description
Differences in mineral metabolism parameter (creatinine) in urine samples.
Time Frame
pre-OP and 6-8 months post-OP
Title
mineral metabolism (urine) 2
Description
Differences in mineral metabolism parameter (phosphate) in urine samples.
Time Frame
pre-OP and 6-8 months post-OP
Title
mineral metabolism (urine) 3
Description
Differences in mineral metabolism parameter (calcium) in urine samples.
Time Frame
pre-OP and 6-8 months post-OP
Title
mineral metabolism (urine) 4
Description
Differences in mineral metabolism parameter (magnesium) in urine samples.
Time Frame
pre-OP and 6-8 months post-OP
Title
mineral metabolism (urine) 5
Description
Differences in mineral metabolism parameter (desoxypyridinoline) in urine samples.
Time Frame
pre-OP and 6-8 months post-OP
Title
metabolomic patterns
Description
Differences in metabolomic patterns assed in blood sample, urine sample, stool sample and exhaled breath.
Time Frame
pre-OP and 6-8 months post-OP
Title
immune response
Description
Differences in immune response biomarkers in blood measured by a cytokine screening assay
Time Frame
pre-OP and 6-8 months post-OP
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ralph Peterli, Prof. Dr. med.
Phone
+ 41 61 777 75 01
Email
ralph.peterli@clarunis.ch
First Name & Middle Initial & Last Name or Official Title & Degree
Claudia Cavelti-Weder, PD Dr. med.
Phone
+41 61 328 63 23
Email
claudia.cavelti-weder@unibas.ch
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anne Christin Meyer-Gerspach, PD Dr. phil. II Dr. habil.
Organizational Affiliation
St. Clara Forschung AG / St. Claraspital AG
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Bettina Wölnerhanssen, PD Dr. med.
Organizational Affiliation
St. Clara Forschung AG / St. Claraspital AG
Official's Role
Principal Investigator
Facility Information:
Facility Name
St Clara Research Ltd, St Claraspital Basel
City
Basel
ZIP/Postal Code
4002
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bettina Wölnerhanssen, MD
Phone
0616858585
Email
forschung@claraspital.ch
First Name & Middle Initial & Last Name & Degree
Jana Distler, MSc
Phone
0616853436
Email
jana.distler@clarspital.ch
12. IPD Sharing Statement
Learn more about this trial
Different Limb Lengths in Gastric Bypass Surgery (SLIM) - Part 3: Metabolism and Inflammation
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