Are gut hormone changes the reason why the long-limb gastric bypass is more effective than the standard limb gastric bypass in improving type 2 diabetes mellitus?
| ISRCTN | ISRCTN15283219 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15283219 |
| Secondary identifying numbers | 19153 |
- Submission date
- 29/07/2015
- Registration date
- 30/07/2015
- Last edited
- 18/08/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English Summary
Background and study aims
Obesity is the main cause of the world wide epidemic of diabetes. Weight loss, or bariatric, surgery produces major and sustained weight loss and is being increasingly used to treat obese diabetic patients. There was initial optimism that these procedures might cure all diabetes. However, the gold-standard operation, standard gastric bypass, effectively cures diabetes in only 4 out of 10 patients. To design a safer and more successful procedure we need to understand how bariatric surgery works to improve diabetes. Hormones from the gut are released when we eat food. They control how the body uses the food it absorbs. For example they release the sugar lowering hormone insulin, and also greatly reduce appetite, which is why one feels less hungry after eating a meal. We have discovered that the good effects of bariatric surgery, and in particular the gastric bypass, are mainly due to increased release of gut hormones, reducing patients appetite and improving the release of insulin. In this project we will be testing a new procedure called the long-limb gastric bypass. It is designed particularly to be better at helping the diabetes in overweight patients, while being as safe as the currently available standard gastric bypass. We now want to show that this new procedure works better than the standard gastric bypass by causing an even bigger increase in the release of gut hormones and therefore insulin.
Who can participate?
Obese adults (aged 18-70 years) with type 2 diabetes.
What does the study involve?
Participants are randomly assigned into one of two groups. Those in group 1 have a standard-limb gastric bypass. Those in group 2 have a long-limb gastric bypass. Using a newly developed technique (mass spectroscopy) we then measure the differences in gut hormone secretion between the new long-limb and the standard gastric bypass. We also use a well-tested insulin sensitivity procedure (glucose clamp), both to confirm and to investigate how and why each participants diabetes has improved after the surgery.
What are the possible benefits and risks of participating?
The measurements we will be making are non-invasive and safe. The only discomfort comes from inserting a cannula to take blood samples.
Where is the study run from?
Imperial College London, Hammersmith Hospital (lead centre) and King’s College London (UK)
When is the study starting and how long is it expected to run for?
August 2015 to February 2018
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
Dr Alex Miras
Contact information
Public
Hammersmith Hospital
Du Cane Road
London
W12 0HS
United Kingdom
 ORCID ID |
0000-0003-3830-3173 |
|---|
Scientific
NIHR Imperial Clinical Research Facility
Imperial Centre for Translational and Experimental Medicine
Section of Investigative Medicine, Division of Diabetes, Endocrinology & Metabolism
Imperial College London
London
W12 0NN
United Kingdom
| Phone | N/A |
|---|---|
| belen.pevida@nhs.net |
Study information
| Study design | Randomized; Double blind; Interventional; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | Are gut hormone changes the reason why the long-limb gastric bypass is more effective than the standard limb gastric bypass in improving type 2 diabetes mellitus? A randomised controlled trial |
| Study acronym | LONG LIMB |
| Study hypothesis | The aim of this study is to show that a new bariatric surgery, the long-limb gastric bypass, is more effective at treating diabetes in people with obesity than the standard-limb gastric bypass. |
| Ethics approval(s) | West London & GTAC, 29/06/2015, ref: 15/LO/0813 |
| Condition | Topic: Diabetes; Subtopic: Type 2; Disease: Diabetic Control, Obesity |
| Intervention | Bariatric surgery, either the standard-limb or long-limb gastric bypass Study Entry : Registration and one or more randomisations |
| Intervention type | Procedure/Surgery |
| Primary outcome measure | Current primary outcomes as of 29/04/2019: Peak plasma GLP-1 concentration as measured by laboratory assays at baseline and at 2 weeks after intervention. Previous primary outcomes as of 10/01/2017: Mechanistic primary outcome: Peak plasma GLP-1 level as measured by laboratory assays at baseline and at the point of 20% weight loss. Clinical primary outcome: Glycated haemoglobin (HbA1c) as measured by laboratory assays at baseline and 1 year. Previous primary outcome: Change in peak GLP-1 level; Timepoint(s): After the mixed meal tolerance test. |
| Secondary outcome measures | Current secondary outcome measures as of 29/04/2019: 1. Plasma levels of glucose, insulin, c-peptide, gut hormones, bile acids, FGF-19 and 21 after the mixed meal tolerance test are measured using laboratory assays at baseline, within 2 weeks and at the point of 20% weight loss 2. Rate of glucose appearance (Ra) and disposal (Rd) in the euglycaemic hyperinsulinaemic clamp is measured using mass spectroscopy/metry at baseline, within 2 weeks and at the point of 20% weight loss. 3. Faecal caloric content is measured using calorimetry at baseline, 20% weight loss and at 1 year 4. 4. Blood, urine and faecal microbial diversity and metabolomics are measured using mass spectroscopy/metry at baseline, within 2 weeks and at the point of 20% weight loss. 5. Total caloric intake and macronutrient composition is measured using dietary records at baseline and at 1 year 6. HbA1c is measured using by laboratory assays at baseline and 1 year 7. Total number of medications are measured using health records at baseline and 1 year 8. Rate of patients achieving diabetes remission is measured using HbA1c and number of medications at 1 year 9. Body weight is measured using scales at baseline and 1 year 10. Systolic, diastolic blood pressure and pulse are measured using a sphygmomanometer at baseline and 1 year 11. Serum fasting lipids are measured using laboratory assays at baseline and 1 year 12. Medical, surgical, nutritional and psychological complications are measured using health records at 1 year 13. Adverse events are measured using health records at 1 year 14. Glycated haemoglobin (HbA1c) as measured by laboratory assays at baseline and 1 year. Previous secondary outcome measures: 1. Plasma levels of glucose, insulin, c-peptide, gut hormones, bile acids, FGF-19 and 21 after the mixed meal tolerance test are measured using laboratory assays at baseline, within 2 weeks and at the point of 20% weight loss 2. Rate of glucose appearance (Ra) and disposal (Rd) in the euglycaemic hyperinsulinaemic clamp is measured using mass spectroscopy/metry at baseline, within 2 weeks and at the point of 20% weight loss. 3. Faecal caloric content is measured using calorimetry at baseline, 20% weight loss and at 1 year 4. 4. Blood, urine and faecal microbial diversity and metabolomics are measured using mass spectroscopy/metry at baseline, within 2 weeks and at the point of 20% weight loss. 5. Total caloric intake and macronutrient composition is measured using dietary records at baseline and at 1 year 6. HbA1c is measured using by laboratory assays at baseline and 1 year 7. Total number of medications are measured using health records at baseline and 1 year 8. Rate of patients achieving diabetes remission is measured using HbA1c and number of medications at 1 year 9. Body weight is measured using scales at baseline and 1 year 10. Systolic, diastolic blood pressure and pulse are measured using a sphygmomanometer at baseline and 1 year 11. Serum fasting lipids are measured using laboratory assays at baseline and 1 year 12. Medical, surgical, nutritional and psychological complications are measured using health records at 1 year 13. Adverse events are measured using health records at 1 year |
| Overall study start date | 01/02/2015 |
| Overall study end date | 14/08/2018 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 70 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 50; UK Sample Size: 50 |
| Total final enrolment | 53 |
| Participant inclusion criteria | 1. Both genders 2. Age 18-70 years 3. Type 2 diabetes mellitus 4. Obesity 5. HbA1c>7.0% 6. On glucose-lowering medication |
| Participant exclusion criteria | 1. Contraindications to bariatric surgery 2. Type 1 diabetes 3. Pregnancy or breastfeeding 4. Recent blood donation |
| Recruitment start date | 31/07/2015 |
| Recruitment end date | 01/02/2017 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
London
W12 0NN
United Kingdom
London
SE5 9RS
United Kingdom
Sponsor information
Hospital/treatment centre
Joint Research Compliance Office
Charing Cross Hospital
Fulham Palace Road
London
W6 8RF
England
United Kingdom
"ROR" |
https://ror.org/041kmwe10 |
|---|
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/02/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | The results of this project will be published in high quality peer-reviewed journals with a wide medical and scientific readership which will allow the detail of the trial to be scrutinized by the medical and scientific community at large. The results of the study will be presented at national and international scientific meetings. All of the applicants are experts in their field and regularly lecture to professional and lay audiences on these topics. We will also disseminate our findings via the press offices of Imperial College London and King’s College London and associated NHS Trusts. Crucially, the clinical results of the trial will be disseminated through our research teams and institutions to NHS England service providers and policymakers. |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 06/11/2020 | 23/09/2021 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Results article | 01/02/2021 | 18/08/2023 | Yes | No |
Editorial Notes
18/08/2023: Publication reference added.
23/09/2021: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added from the reference.
29/04/2019: The primary and secondary outcomes were updated.
31/05/2018: Scientific contact added.
11/01/2017: The primary outcome measures have been updated and the timepoints and methods of measurement have been added to the secondary outcome measures.
12/02/2016: Amended study design by adding the text "Double blind"
