Fermentable carbohydrate and gut hormone release
| ISRCTN | ISRCTN11327221 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11327221 |
| Secondary identifying numbers | 33144 |
- Submission date
- 16/10/2017
- Registration date
- 19/10/2017
- Last edited
- 20/06/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Digestive System
Plain English Summary
Background and study aims
In England, 60% of the adult population is overweight or obese. There is an urgent need to understand how dietary components effect appetite regulation. Previous research has demonstrated that increased dietary intake of fermentable carbohydrate promotes weight loss. Fermentable carbohydrates are not digested in the small intestine (the ileum) and therefore enter the large intestine (the colon) where they are fermented by the resident bacteria producing short chain fatty acids (SCFAs). SCFAs have been shown to stimulate the release of appetite suppressing hormones called PYY and GLP-1 from the colon. Understanding how the gut senses ingested food to reduce food intake, will permit the design of foods that make people feel full. The aim of this study is to look at the effects of different types of carbohydrates on gut contents and the effects this has on how hungry people feel. This may be important in terms of controlling body weight and therefore preventing obesity.
Who can participate?
Adults aged 18 and to 65 who have a BMI of 18-30 kg/m2.
What does the study involve?
This study involves three separate 4-day inpatient assessments. For each 4-Day study visit, participants stay at the Clinical Research Facility at Hammersmith Hospital for three nights. During each study visit participants are provided with a diet containing different types and amounts of carbohydrate rich foods (sugars, starchy foods, fruits and vegetables). They receive the different carbohydrate diets in a random order. The amounts of dietary fat and protein will be the same at each of the 3 study visits. On Day 1 of the study visit, participants have a tube placed through their nose by a trained medical professional under fluoroscopy. Fluoroscopy is a type of medical imaging that shows a continuous X-ray image on a monitor, much like an X-ray movie. The end of this tube lies within the small intestine (ileum) allowing us to collect and measure the contents of the gut.
On the morning of Day 3, participants are provided with a test meal at approximately 09:00. Before the breakfast and for 8 hours afterwards samples will be collected from the tube to measure the gut contents. On the morning of day 4, a small plastic cannula tube is inserted into a vein in one arm. A vein is the type of blood vessel commonly used for taking blood samples. The cannula tube is used to take blood samples to measure the levels of hormones which control hunger in the body. During each study visit approximately 100 ml of blood (5 tablespoons of blood) is collected. At approximately 09:00 a test meal is provided and gut content samples and blood samples are collected throughout an 8 hour study period. After each sample is collected participants are asked to fill in a chart describing how hungry they feel. At approximately 17:00 on Day 4, the nasal tube and cannula tube are removed and participants are free to go home. In addition, participants are also asked to collect a stool sample on each day of the 4-Day study visit.
What are the possible benefits and risks of participating?
Taking part in the study will provide no direct benefit for participants. If any of the screening questionnaires or blood tests reveal any medical problems (e.g. diabetes, kidney or liver problems), the participant’s GP will be informed so that they can coordinate further care, arrange any further tests, and refer the participant on to Hospital Doctors if necessary. Insertion of the cannula on each of the study visits may cause minor discomfort or superficial bruising. Serious risks associated with the insertion of the tubes are very rare and almost negligible. These risks include bleeding, perforation or damage to the base of the skull. Minor discomfort of the back of the throat does occur in the majority of patients and may result transiently in a sore mouth, thirst, swallowing difficulties or hoarseness. The fluoroscopy procedure will expose participants to a small dose of radiation. The mean effective dose from each nasogastric tube procedure is equivalent to 2.8 months of natural background radiation (the same amount as you would be exposed to walking around outside) and would increase the risk of inducing cancer by 0.0025% (or 1 in 40,000). The minimum number of fluoroscopy procedures that will be conducted is 3. The maximum number of fluoroscopy procedures that will be conducted is 6.
Where is the study run from?
Imperial College London (UK)
When is the study starting and how long is it expected to run for?
June 2014 to June 2019
Who is funding the study?
Biotechnology & Biological Sciences Research Council (UK)
Who is the main contact?
Miss Claire Byrne
claire.byrne@imperial.ac.uk
Contact information
Scientific
Nutrition and Dietetic Research Group
6th Floor Commonwealth Building
Faculty of Medicine
Imperial College Hammersmith Campus
Du Cane Road
London
W12 0NN
United Kingdom
 ORCID ID |
0000-0001-7578-6237 |
|---|---|
| Phone | +44 2083833242 |
| claire.byrne@imperial.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Prevention, Dietary |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Understanding the interplay between fermentable carbohydrates and gut hormone release |
| Study hypothesis | The aim of this study is to determine the effects of diets containing different amounts of fermentable carbohydrates on ileum contents and to determine the subsequent impact on appetite responses and PYY and GLP-1 release from the colon. |
| Ethics approval(s) | London-Bloomsbury REC, 08/03/2017, ref: 17/LO/0354 |
| Condition | Obesity |
| Intervention | This is a randomised crossover study during which healthy volunteers are clinical research facility inpatients for four days on three separate occasions. On day one of the study, a naso-enteric tube is inserted through the nose, with a small balloon at the terminal end which is inflated and used to carry the tube through the small intestine by peristalsis. Once the tube reaches the terminal ileum, the balloon is deflated and the tube is restrained from additional movement for the rest of the 4-day study visit. During the three separate study visits, volunteers will be provided with different diets differing in carbohydrate quality. All the diets have similar macronutrient content (55% energy from carbohydrate, 30% energy from fat, 15% energy from protein). In a randomised order, volunteers receive: 1. DIET 1: Highly refined and processed carbohydrate: Foods will be low in fibre and intact cell structures. 2. DIET 2: High fibre with high intake cellular structure: Will contain foods with resistant cell structures such as beans, nuts, minimally processed wholegrain wheat cereal and vegetables. 3. DIET 3: High fibre with disrupted cellular structure: The same as DIET 2, but the food is processed in order to disrupt the cell structure. Volunteers are fed one of the diets over the 4-day study period. The diet starts on Day 1 and end on Day 4. The collection of ileal samples start on day 3. On day 4, ileal samples are collected as on day 3 and are matched with blood sampling and visual analogue scales (VAS) to assess appetite responses. Volunteers will also be asked to collect a stool sample on each day of the 4-day study period. |
| Intervention type | Other |
| Primary outcome measure | 1. Metabolic profiling of ileal samples is measured using 1H NMR spectroscopy, ultra-performance LC-MS and GC-MS on Day 3 and Day 4 at baseline and 60, 120, 180, 240, 300, 360, 420 and 480 min following breakfast 2. Microbiological profiling of ileal samples is measured using 16S sequencing on Day 3 and Day 4 at baseline and 60, 120, 180, 240, 300, 360, 420 and 480 min following breakfast |
| Secondary outcome measures | Current secondary outcome measures as of 13/09/2018: 1. Metabolic and hormonal profiling of blood samples is measured using radioimmunoassay, 1H NMR spectroscopy, ultra-performance LC-MS and GC-MS on Day 4 at baseline and 60, 120, 180, 240, 300, 360, 420 and 480 min following breakfast 2. Microbiological profiling of faecal samples is measured using 16S sequencing on each day of the 4-day study visit 3. Subjective appetite is measured using visual analogue scales on Day 4 at baseline and 60, 120, 180, 240, 300, 360, 420 and 480 min following breakfast 4. Nausea is measured using visual analogue scales on Day 4 at baseline and 60, 120, 180, 240, 300, 360, 420 and 480 min following breakfast 5. Metabolic profiling of faecal samples is measured using 1H NMR spectroscopy on each day of the intervention 6. Detection of plant structures, cell structures and starch granules in ileal samples is measured by microscopy on Day 3 and Day 4 of the intervention Previous secondary outcome measures: 1. Metabolic and hormonal profiling of blood samples is measured using radioimmunoassay, 1H NMR spectroscopy, ultra-performance LC-MS and GC-MS on Day 4 at baseline and 60, 120, 180, 240, 300, 360, 420 and 480 min following breakfast 2. Microbiological profiling of faecal samples is measured using 16S sequencing on each day of the 4-day study visit 3. Subjective appetite is measured using visual analogue scales on Day 4 at baseline and 60, 120, 180, 240, 300, 360, 420 and 480 min following breakfast 4. Nausea is measured using visual analogue scales on Day 4 at baseline and 60, 120, 180, 240, 300, 360, 420 and 480 min following breakfast |
| Overall study start date | 01/06/2014 |
| Overall study end date | 01/06/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 65 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 15; UK Sample Size: 15 |
| Total final enrolment | 16 |
| Participant inclusion criteria | 1. Male or female 2. Age between 18-65 years (inclusive) 3. Body mass index (BMI) of 18-30 kg/m2 4. Willingness and ability to give written informed consent and willingness and ability to understand, to participate and to comply with the study requirements |
| Participant exclusion criteria | 1. Abnormal ECG 2. Screening blood results outside of normal reference values 3. Weight change of > = 5kg in the preceding 2 months 4. Current smokers 5. History of substance abuse and/or excess alcohol intake 6. Pregnancy 7. Diabetes 8. Cardiovascular disease 9. Cancer 10. Gastrointestinal disease e.g. inflammatory bowel disease or irritable bowel syndrome 11. Kidney disease 12. Liver disease 13. Pancreatitis 14. Started new medication within the last 3 months likely to interfere with energy metabolism, appetite regulation and hormonal balance, including: anti-inflammatory drugs or steroids, antibiotics, androgens, phenytoin, erythromycin or thyroid hormones 15. Participation in a research study in the 12 week period prior to entering this study 16. Any blood donation within the 12 week period prior to entering this study |
| Recruitment start date | 23/08/2017 |
| Recruitment end date | 01/04/2019 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
W12 0NN
United Kingdom
Sponsor information
Hospital/treatment centre
Joint Research Compliance Office
London
W12 0NN
England
United Kingdom
"ROR" |
https://ror.org/041kmwe10 |
|---|
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- UKRI - Biotechnology And Biological Sciences Research Council, BBSRC UK, BBSRC
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/10/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Other |
| Publication and dissemination plan | Planned publication in a high-impact peer reviewed journal within 12 months of the overall trial end date |
| IPD sharing plan | The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 05/03/2019 | 09/06/2020 | Yes | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Statistical Analysis Plan | 10/08/2023 | No | No | ||
| Results article | 24/10/2015 | 16/08/2023 | Yes | No | |
| Results article | 17/11/2015 | 16/08/2023 | Yes | No | |
| Results article | 19/06/2024 | 20/06/2024 | Yes | No |
Additional files
Editorial Notes
20/06/2024: Publication reference added.
16/08/2023: Publication references added.
10/08/2023: Statistical analysis plan uploaded. The intention to publish date was changed from 01/06/2020 to 01/10/2023.
09/06/2020: Publication reference added.
17/05/2019: The total final enrolment was added.
03/04/2019: The condition has been changed from "Specialty: Metabolic and endocrine disorders, Primary sub-specialty: Metabolic and endocrine disorders; UKCRC code/ Disease: Cancer/ Malignant neoplasms of digestive organs, Metabolic and Endocrine/ Obesity and other hyperalimentation, Stroke/ Cerebrovascular diseases, Oral and Gastrointestinal/ Other diseases of the digestive system, Cardiovascular/ Pulmonary heart disease and diseases of pulmonary circulation" to "Obesity" following a request from the NIHR.
18/02/2019: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/01/2019 to 01/04/2019.
2. The overall trial end date was changed from 01/04/2019 to 01/06/2019.
3. The intention to publish date was changed from 01/04/2020 to 01/06/2020.
15/11/2018: The recruitment end date was changed from 01/10/2018 to 31/01/2019.
13/09/2018: The secondary outcome measures have been changed.
26/10/2017: Internal review.
