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
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Protocol serial number	19153
Sponsor	Imperial College London
Funder	National Institute for Health Research

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

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

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

Dr Alex Miras
Public

Hammersmith Hospital
Du Cane Road
London
W12 0HS
United Kingdom

ORCID ID	0000-0003-3830-3173

Dr Belen Perez Pevida
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
Email	belen.pevida@nhs.net

Study information

Primary study design	Interventional
Study design	Randomized; Double blind; Interventional; Design type: Treatment
Secondary study design	Randomised controlled trial
Study type	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 objectives	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
Health condition(s) or problem(s) studied	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(s)	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.
Key secondary outcome measure(s)	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
Completion date	14/08/2018

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	70 Years
Sex	All
Target sample size at registration	50
Total final enrolment	53
Key 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
Key exclusion criteria	1. Contraindications to bariatric surgery 2. Type 1 diabetes 3. Pregnancy or breastfeeding 4. Recent blood donation
Date of first enrolment	31/07/2015
Date of final enrolment	01/02/2017

Locations

Countries of recruitment

United Kingdom
England

Study participating centres

Imperial College London, Hammersmith Hospital (lead centre)

Du Cane Road
London
W12 0NN
United Kingdom

King’s College London

Denmark Hill
London
SE5 9RS
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
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
Results article		01/02/2021	18/08/2023	Yes	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

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"