Condition category
Nutritional, Metabolic, Endocrine
Date applied
26/09/2014
Date assigned
26/09/2014
Last edited
24/01/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Dietary fibre is anything that we eat that our body is unable to breakdown or digest. However, in our guts we have trillions of bacteria, collectively known as the gut microbiota, that are able to ‘eat’ the fibre in our food. This process allows the gut microbiota to produce energy to survive and grow. The main ‘end-products’ of this process are called short chain fatty acids (SCFA) and scientific work is continuing to link these SCFA with improvements in human health. An increased production of SCFA in the gut has been linked to reductions in body weight and improvements in blood glucose levels. We have developed a novel dietary supplement called a propionate-ester that increases the amounts of a SCFA called propionate produced in the gut. Our previous work has shown the feeding the propionate-ester to overweight and obese humans prevented further gains in body weight and reduced the amount of fat in the liver. The current project has two separate studies. The aim of study one is to investigate the effect of the propionate-ester on blood glucose levels in overweight adults. The aim of study two is to look at the effect of the propionate-ester on the amounts of liver fat in individuals with a previous diagnosis of non-alcoholic fatty liver disease (a condition where individuals have higher levels of liver fat).

Who can participate?
Adults aged 18 to 65 who have a BMI between 25-41 kg/m2.

What does the study involve?
If you participate in Study 1, you will be asked to complete three supplementation periods lasting 42 days. During each supplementation period you will be provided with a different dietary fibre to add to your diet. The dietary fibres are all in a powder form that mixes easily into your normal food and drink. At the end of each 42 day period you will be asked to attend our Clinical Research Facility where we will collect blood samples to look at the effects of each dietary fibre on your blood glucose levels. If you participate in Study 2, you will be asked to complete a single 42 day supplementation period. You will be provided with a dietary fibre to mix into your normal diet. Before and at the end of the 42 day period you will be asked to attend our Clinical Research Facility where we will conduct a liver scan to look at the effects of the dietary fibre on liver fat levels.

What are the possible benefits and risks of participating?
There are no direct benefits or risks of taking part in either study.

Where is the study run from?
Imperial College London (UK)

When is the study starting and how long is it expected to run for?
February 2014 to July 2017

Who is funding the study?
Biotechnology and Biological Sciences Research Council (BBSRC) (UK)

Who is the main contact?
Dr Edward Chambers (Scientific)
e.chambers@imperial.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Edward Chambers

ORCID ID

Contact details

Du Cane Road
London
W12 0NN
United Kingdom
-
e.chambers@imperial.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

16734

Study information

Scientific title

Effect of increased propionate in the colon on appetite and glucose homeostasis

Acronym

Study hypothesis

Increased intake of dietary fibre has been associated with reduced appetite and weight loss. In particular, evidence suggests that the fermentable component of dietary fibre is critical in mediating these satiating effects. The short chain fatty acids (SCFAs) produced by microbial fermentation of dietary fibre in the colon have been shown to stimulate the release of appetite suppressing hormones peptide YY (PYY) and glucagon like peptide-1 (GLP-1). Increasing colonic SCFA levels is therefore an attractive target for appetite modulation. To overcome the unpalatably high levels of fermentable dietary fibre needed to significantly increase colonic SCFA levels, we have developed a novel delivery system targeting the release of gram quantities of the SCFA propionate in the human colon. A propionate ester has been produced whereby propionate is chemically bound by an ester bond to inulin, a natural dietary fibre composed mainly of fructose. The majority of propionate bound to inulin should only be released when the inulin polymer is fermented by the colonic microbiota, thus providing targeted colonic delivery. Our previous studies (Effect of Fibre Products on Appetite and Weight; REC Reference: 08/H0707/99) have found that acute ingestion of propionate ester increases plasma PYY and GLP-1 concentrations and reduces food intake. Furthermore, long-term (24 weeks) ingestion of propionate ester significantly reduced body weight gain and the development of abdominal adipose tissue, major risk factors in the development of insulin resistance and diabetes. The current protocol comprises two follow-on studies which have the following aims:

1. Confirm the appetite suppressing effects of propionate ester when incorporated into a food product.
2. Assess the effects of propionate ester on glucose and lipid metabolism.
Added 24/01/2018:
3. Investigate the impact of propionate ester on hepatic steatosis in adults with non-alcoholic fatty liver disease (NAFLD).

Ethics approval

London – Brent, 19/05/2014, ref: 14/LO/0645

Study design

Randomised; Interventional; Design type: Not specified

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

GP practices

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Topic: Primary Care, Metabolic and endocrine disorders; Subtopic: Metabolic and Endocrine (all Subtopics), Metabolic and endocrine disorders; Disease: Metabolic & Endocrine (not diabetes), All Diseases

Intervention

Study 1: Cellulose, Control; Inulin, Control; Inulin-propionate ester, Inulin-propionate ester; Study Entry : Single Randomisation only

Added 24/01/2018:
Study 2: Inulin, Control; Inulin-propionate ester, Inulin-propionate ester; Study Entry : Single Randomisation only

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measure

Study 1: Glucose homeostasis; Timepoint(s): End of each 6 week intervention

Added 24/01/2018:
Study 2: Intrahepatocellular lipid content

Secondary outcome measures

Study 1: Body composition; Timepoint(s): End of each 6 week intervention

Overall trial start date

01/02/2014

Overall trial end date

01/07/2017

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Study 1:
1. Healthy volunteers aged 18-65
2. Male or female
3. Body mass index (weight in kg divided by height in metre squared) of 25-40 kg/m2

Added 24/01/2018:
Study 2:
1. Male or female aged 18-65 years
2. Body mass index (weight in kg divided by height in metre squared) of BMI of 20-40 kg/m2
3. Histological confirmation of NAFLD in previous 5 years.
4. Controlled blood glucose levels (HbA1c <48 mmol/mol)

Participant type

Healthy volunteer

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 40; UK Sample Size: 40

Participant exclusion criteria

Study 1 and Study 2:
1. Weight change of more than 3kg in the preceding 3 months
2. Current smokers
3. Substance abuse
4. Excess alcohol intake
5. Pregnancy
6. Diabetes
7. Cardiovascular disease
8. Cancer
9. Gastrointestinal disease e.g. inflammatory bowel disease or irritable bowel syndrome
10. Kidney disease
11. Liver disease
12. Pancreatitis
13. Use of medications including: antiinflammatory drugs or steroids, androgens, phenytoin, erythromycin or thyroid hormones

Study 2 has the additional exclusion criteria:
14.• Metallic or magnetic implants such as pacemakers
•15. Claustrophobia

Recruitment start date

13/08/2014

Recruitment end date

03/03/2016

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Imperial College London
London
W12 0NN
United Kingdom

Sponsor information

Organisation

Imperial College London (UK)

Sponsor details

Joint Research Compliance Office
Charing Cross Hospital
Fulham Palace Road
London
W6 8RF
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Research council

Funder name

Biotechnology and Biological Sciences Research Council (BBSRC); Grant Codes: BB/L004259/1

Alternative name(s)

BBSRC

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal. Intention to publish in 2018.

IPD sharing statement:
The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication. The anonymised datasets will be provided as supplementary material in planned publications.

Intention to publish date

01/09/2016

Participant level data

Other

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

24/01/2018: The following updates were made: 1. The overall trial start date has been updated from 13/08/2014 to 01/02/2014. The recruitment end date has been updated from 01/07/2017 to 03/03/2016. 2. The ethics board has been added. 3. The publication and dissemination sharing plans have been added. 4. The participant level data sharing statement has been added. 5. The Plain English Summary has been added. 6. The interventions have been updated 7. The hypothesis has been updated. 8. The outcome measures have been updated. 9. The inclusion criteria has been updated.