The Endocrine Secretome After Gastric Bypass Surgery

Obesity, Morbid Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03093298
• Other study ID #: H-6-2014-047
• Status: Completed
• Phase: N/A
• First received: March 12, 2017
• Last updated: March 21, 2017
• Start date: December 12, 2014
• Est. completion date: December 13, 2016

Study information

• Verified date: March 2017
• Source: University Hospital, Gentofte, Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: December 13, 2016
• Est. primary completion date: December 13, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Obesity, Morbid
• Type2 Diabetes

Intervention

Other:
• Enteroscopy with biopsy sampling and mixed meal test
Enteroscopies with biopsy retrieval and mixed meal tests with blood sampling before and after Roux-en-Y gastric bypass surgery

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Filip Krag Knop	Sanofi

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Altered gene expression in the endocrine secretome following Roux-en-Y gastric bypass surgery		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)