Characterization of the incretin response and microbiota following bariatric surgery, and its role for weight loss – a search for polytherapeutic strategies to combat obesity and ultimately rival surgery
| ISRCTN | ISRCTN11764561 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11764561 |
| Secondary identifying numbers | nr1 |
- Submission date
- 27/02/2017
- Registration date
- 03/04/2017
- Last edited
- 06/03/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English summary of protocol
Background and study aims
Obesity represents a global epidemic, and increases the risk of developing Type 2 Diabetes Mellitus (T2DM), hence the introduction of the term “diabesity”. The most effective and long-lasting solution for severe obesity is bariatric surgery. Two widely used types of bariatric surgery are gastric bypass and gastric sleeve. Gastric bypass involves re-routing the digestive system past most of the stomach, so less food is digested and it takes much less to feel full. Gastric sleeve involves removing some of the stomach to reduce the amount of food that's required to feel full. Obesity causes changes in the bacteria that live in the gut (microbiota). After bariatric surgery there are changes in the gut microbiota and in intestinal hormones (e.g. GLP-1) that control satiety (fullness) and food intake. Although gut microbiota changes have been suggested to alter levels of GLP-1, the mechanism and its importance in bariatric surgery remain to be determined. The aim of this study is to investigate the changes in the gut microbiota after two different types of bariatric surgery, as well as the relationship with blood levels of GLP-1.
Who can participate?
Women aged 18-65 who are severely obese and not diabetic
What does the study involve?
Participants are randomly allocated into two groups to undergo either gastric bypass or gastric sleeve surgery. Participants are followed for 6 months after surgery, and fecal and blood samples are collected before surgery as well as 3 and 6 months after surgery. Meal-stimulated blood GLP-1 levels are measured before and 3 and 6 months after surgery.
What are the possible benefits and risks of participating?
This study may increase knowledge of the mechanisms controlling obesity and help develop better and less invasive treatments, as well as providing more information regarding the participant’s own outcome of surgery and a more extensive follow-up after surgery. The risks of participating can be considered low as participation only involves repeated blood sampling.
Where is the study run from?
Södertälje Sjukhus AB (Sweden)
When is the study starting and how long is it expected to run for?
February 2017 to September 2020
Who is funding the study?
1. Mats Kleberg Foundation (Sweden)
2. Fredrik och Ingrid Thurings Stiftelse (Sweden)
3. Tore Nilsons Stiftelse för Medicinsk Forskning (Sweden)
Who is the main contact?
Dr Camilla Krizhanovskii
Contact information
Scientific
Lagmansvägen 15
Södertälje
15286
Sweden
 ORCID ID |
0000-0003-2195-165X |
|---|
Study information
| Study design | Randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | No participant information sheet available |
| Scientific title | Characterization of the incretin response and microbiota in women before an after bariatric surgery, aiming to determine how the microbiota regulates metabolism, and its role for weight loss: a randomized controlled trial |
| Study objectives | Alteration of gut microbiota following bariatric surgery contributes to its efficacy as a weight loss treatment through modulation of the secretion of the anorectic hormone GLP-1. |
| Ethics approval(s) | Regionala etikprövningsnämnden i Stockholm (regional ethics board in Stockholm), 26/08/2015, ref: 2015/795-31/2 |
| Health condition(s) or problem(s) studied | Obesity |
| Intervention | Non-diabetic patients with severe obesity (that is, BMI >40 kg/m. or BMI >35 kg/m. with comorbidities) will be randomized into two groups receiving either gastric bypass (RYGB) or gastric sleeve. Patients will be followed for 6 months post-surgery, and fecal and blood samples will be collected before surgery, as well as 3 and 6 months after surgery. Meal stimulated GLP-1 plasma levels will be determined prior to and 3 and 6 months after surgery. The primary endpoint is the proportion of subjects achieving a 15% relative change in meal stimulated GLP-1 plasma levels following gastric bypass surgery (RYGB)/gastric sleeve compared to pre-surgical meal stimulated GLP-1 release, as assessed by GLP-1 specific ELISA of serum samples. Secondary endpoints are whether a 15% weight reduction of presurgical body weight is observed following gastric bypass surgery (RYGB)/sleeve. |
| Intervention type | Procedure/Surgery |
| Primary outcome measure | 1. Plasma GLP-1, measured using the meal tolerance test and GLP-1 specific ELISA of serum samples 2. Gut microbiota composition, analyzed from fecal samples Timepoints: before 10-day diet, after 10-day diet/before surgery, 3 months after surgery, 6 months after surgery |
| Secondary outcome measures | 1. Plasma inflammatory markers, analyzed by specific ELISAs 2. Lipid profile, determined by commercially available HDL and LDL/VLDL Cholesterol Assay Kits, Free Fatty Acid Quantification Kit, as well as Triglyceride Quantification Kit Timepoints: before 10-day diet, after 10-day diet/before surgery, 3 months after surgery, 6 months after surgery |
| Overall study start date | 01/10/2016 |
| Completion date | 01/09/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 65 Years |
| Sex | Female |
| Target number of participants | 30 subjects (15 in each group) |
| Key inclusion criteria | 1. Obese non-diabetic females 2. 18-65 years of age 3. Signed informed consent form |
| Key exclusion criteria | 1. Type 2 diabetes 2. Any history of receiving GLP-1 analogues or DPP-4 inhibitors 3. Previous treatment with insulin (any regimen) within 3 months 4. Current or history of drug and alcohol abuse |
| Date of first enrolment | 27/02/2017 |
| Date of final enrolment | 30/03/2020 |
Locations
Countries of recruitment
- Sweden
Study participating centre
Sweden
Sponsor information
Hospital/treatment centre
Lagmansvägen 15
Södertälje
15286
Sweden
"ROR" |
https://ror.org/0376t7t08 |
|---|
Funders
Funder type
Charity
No information available
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Fredrik and Ingrid Thurings Foundation
- Location
- Sweden
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Tore Nilsson Foundation, Tore Nilsson Fond
- Location
- Sweden
Results and Publications
| Intention to publish date | 30/11/2020 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer reviewed journal |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Camilla Krizhanovskii |
Editorial Notes
06/03/2019: The following changes were made to the trial record:
1. The recruitment end date was changed from 30/09/2018 to 30/03/2020.
2. The overall trial end date was changed from 01/12/2018 to 01/09/2020.
3. The intention to publish date was changed from 30/11/2019 to 30/11/2020.
05/03/2018: The following updates were made to the trial record:
1. Recruitment end date changed from 27/02/2018 to 30/09/2018.
2. Overall trial end date changed from 27/02/2018 to 1/12/2018.
3. Intention to publish date changed from 01/12/2018 to 30/11/2019.
07/03/2018: Overall trial start date changed from 27/02/2017 to 01/10/2016.
