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The Endocrine Secretome After Gastric Bypass Surgery

Primary Purpose

Obesity, Morbid, Type2 Diabetes

Status

Completed

Phase

Not Applicable

Locations

Study Type

Interventional

Intervention

Enteroscopy with biopsy sampling and mixed meal test

About this trial

This is an interventional basic science trial for Obesity, Morbid

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Obese subjects referred for assessment of eligibility for RYGB surgery
Age ≥25 and ≤ 60 years
Able to understand written patient information and obtained signed informed consent
Type 2 diabetes patients treated with lifestyle, metformin and/or sulfonylurea will be allowed participation.

Exclusion Criteria:

Diagnosis of diabetes mellitus type 1
Individuals being categorized as subjects with type 2 diabetes according to ADA 2014 criteria AND currently being treated with DPPIV inhibitors, GLP-1 agonists, insulin and/or SGLT2 inhibitors.
Co-morbidities that, in the discretion of the investigators, exclude study participation such as chronic obstructive pulmonary disease (COPD) stage III, significant cardiac arrhythmias etc.
Previous gastrointestinal surgery (excluding cholecystectomy and appendectomy).
Gastrointestinal conditions making the subject unsuitable to participate in the study such as ulcerative colitis, Crohn´s disease, clinically significant food allergies, candidiasis etc.
Chronic systemic inflammatory diseases (e.g,. rheumatoid arthritis) and other conditions significantly affecting inflammation status or immunoregulation (severe allergies, status post transplantation etc.)
Chronic, planned or likely-to-be-required parenteral or oral corticosteroid medication during the study period, or (parenteral or oral) corticosteroid medication <4 weeks prior to screening
Chronic infectious diseases such as hepatitis, HIV etc.
Anaemia with a haemoglobin value 6.2 mmol/L (<10 g/dL) for women and 7.4 mmol/L (< 12 g/dL) for men at time of screening
Clinically significant liver or kidney function impairment, or other laboratory findings leading to the diagnosis of clinically relevant disorders (severe thyroid dysfunction etc)
Planned elective surgery (other than bariatric surgery) during the study period with the exception of dermatosurgical, ENT (ear, nose, throat) or dental procedures not requiring general anaesthesia and/or perioperative antibiotic treatment
Abuse of alcohol and/or drugs, or any other co-existing conditions that will make the subject unsuitable to participate in the study, as deemed by the investigators
Pregnancy or desire to become pregnant during the study period

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Obesity

Arm Description

Enteroscopies with biopsy retrieval and mixed meal tests with blood sampling

Outcomes

Primary Outcome Measures

Altered gene expression in the endocrine secretome following Roux-en-Y gastric bypass surgery

Secondary Outcome Measures

Full Information

NCT ID

NCT03093298

First Posted

March 12, 2017

Last Updated

March 21, 2017

Sponsor

Filip Krag Knop

Collaborators

Sanofi

1. Study Identification

Unique Protocol Identification Number

NCT03093298

Brief Title

The Endocrine Secretome After Gastric Bypass Surgery

Official Title

Searching for Altered Gene Expression in the Endocrine Secretome Following Roux-en-Y Gastric Bypass Surgery

Study Type

Interventional

2. Study Status

Record Verification Date

March 2017

Overall Recruitment Status

Completed

Study Start Date

December 12, 2014 (Actual)

Primary Completion Date

December 13, 2016 (Actual)

Study Completion Date

December 13, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Filip Krag Knop

Collaborators

Sanofi

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

Examination of the molecular phenotype and composition of endocrine cells in the gastrointestinal tract correlated to analyses of blood for hormones/analytes before and after Roux-en-Y gastric bypass surgery in morbidly obese individuals both with and without type 2 diabetes

Detailed Description

Enteroscopy was conducted during sedation with Propofol®. The pre-surgical sampling included biopsies retrieved from the stomach and at the expected site of anastomosis. During RYGB surgery, a ~1 cm gut tissue sample was removed at the site of anastomosis. The post-surgical enteroscopy ~3 months after RYGB surgery included biopsies taken from the gastric pouch, the alimentary limb, the biliopancreatic limb and common channel. One sample from each location was immersion-fixated in formalin for subsequent histological analyses and one sample was placed in a tube with RNA-preserving media for mRNA expression analysis. Remaining samples were snap-frozen and stored at -80°C until further processing. Enteroendocrine cells were identified and isolated from biopsies obtained at several sites in the small intestine by using immunohistochemistry and laser capture technology. Isolated individual enteroendocrine cells were extensively characterised by next generation sequencing (Illumina NGS). The participants also went through four mixed meal tests with blood sampling performed: before an 8 % diet-induced weight loss was initiated and one week before/one week after/3 months after RYGB surgery. Blood was sampled at several specific time points. The plasma, serum and urine collected from study participants before and after RYGB surgery will be analysed for biomarkers/analytes and correlated with clinical data (weight, BMI, waist/hip ratio, blood pressure) and molecular phenotype found in gut samples. To study changes in gut bacteria (microbiota) composition stool samples were collected during the study and will be analysed for microbiota composition by means of bacterial DNA sequencing.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Obesity, Morbid, Type2 Diabetes

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

28 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Obesity

Arm Type

Experimental

Arm Description

Enteroscopies with biopsy retrieval and mixed meal tests with blood sampling

Intervention Type

Other

Intervention Name(s)

Enteroscopy with biopsy sampling and mixed meal test

Intervention Description

Enteroscopies with biopsy retrieval and mixed meal tests with blood sampling before and after Roux-en-Y gastric bypass surgery

Primary Outcome Measure Information:

Title

Altered gene expression in the endocrine secretome following Roux-en-Y gastric bypass surgery

Time Frame

Each participant went through six study days (two mixed meal tests and one enteroscopy procedure before and after Roux-en-Y gastric bypass surgery, respectively)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Obese subjects referred for assessment of eligibility for RYGB surgery Age ≥25 and ≤ 60 years Able to understand written patient information and obtained signed informed consent Type 2 diabetes patients treated with lifestyle, metformin and/or sulfonylurea will be allowed participation. Exclusion Criteria: Diagnosis of diabetes mellitus type 1 Individuals being categorized as subjects with type 2 diabetes according to ADA 2014 criteria AND currently being treated with DPPIV inhibitors, GLP-1 agonists, insulin and/or SGLT2 inhibitors. Co-morbidities that, in the discretion of the investigators, exclude study participation such as chronic obstructive pulmonary disease (COPD) stage III, significant cardiac arrhythmias etc. Previous gastrointestinal surgery (excluding cholecystectomy and appendectomy). Gastrointestinal conditions making the subject unsuitable to participate in the study such as ulcerative colitis, Crohn´s disease, clinically significant food allergies, candidiasis etc. Chronic systemic inflammatory diseases (e.g,. rheumatoid arthritis) and other conditions significantly affecting inflammation status or immunoregulation (severe allergies, status post transplantation etc.) Chronic, planned or likely-to-be-required parenteral or oral corticosteroid medication during the study period, or (parenteral or oral) corticosteroid medication <4 weeks prior to screening Chronic infectious diseases such as hepatitis, HIV etc. Anaemia with a haemoglobin value 6.2 mmol/L (<10 g/dL) for women and 7.4 mmol/L (< 12 g/dL) for men at time of screening Clinically significant liver or kidney function impairment, or other laboratory findings leading to the diagnosis of clinically relevant disorders (severe thyroid dysfunction etc) Planned elective surgery (other than bariatric surgery) during the study period with the exception of dermatosurgical, ENT (ear, nose, throat) or dental procedures not requiring general anaesthesia and/or perioperative antibiotic treatment Abuse of alcohol and/or drugs, or any other co-existing conditions that will make the subject unsuitable to participate in the study, as deemed by the investigators Pregnancy or desire to become pregnant during the study period

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Filip Knop, MD, prof.

Organizational Affiliation

Gentofte Hospital, University of Copenhagen

Official's Role

Principal Investigator

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

33150746

Citation

Jorsal T, Christensen MM, Mortensen B, Nygaard EB, Zhang C, Rigbolt K, Wandall E, Langholz E, Friis S, Worm D, Floyd A, Helgstrand F, Stoving RK, Aldries AR, Juhl CB, Ostergaard T, Rydborg T, Forman JL, Sorensen F, Schmidt T, Falkenhahn M, Musholt PB, Theis S, Larsen PJ, Rehfeld JF, Vrang N, Jelsing J, Vilsboll T, Knop FK. Gut Mucosal Gene Expression and Metabolic Changes After Roux-en-Y Gastric Bypass Surgery. Obesity (Silver Spring). 2020 Nov;28(11):2163-2174. doi: 10.1002/oby.22973.

Results Reference

derived

PubMed Identifier

31276156

Citation

Jorsal T, Wewer Albrechtsen NJ, Christensen MM, Mortensen B, Wandall E, Langholz E, Friis S, Worm D, Orskov C, Stoving RK, Andries A, Juhl CB, Sorensen F, Forman JL, Falkenhahn M, Musholt PB, Theis S, Larsen PJ, Holst JJ, Vrang N, Jelsing J, Vilsboll T, Knop FK. Investigating Intestinal Glucagon After Roux-en-Y Gastric Bypass Surgery. J Clin Endocrinol Metab. 2019 Dec 1;104(12):6403-6416. doi: 10.1210/jc.2019-00062.

Results Reference

derived

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The Endocrine Secretome After Gastric Bypass Surgery

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