Condition category
Nutritional, Metabolic, Endocrine
Date applied
17/10/2012
Date assigned
18/10/2012
Last edited
05/12/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Within the last 20 years, population levels of obesity have greatly increased in many countries throughout the world. This trend has prompted great interest in the regulation of feeding and hunger in humans. There is some evidence that patients with obesity and type 2 diabetes mellitus (T2DM) may have abnormalities affecting the regulation of appetite. A particularly promising area in this field involves the study of gut hormones, particularly GLP-1, which promotes insulin secretion and satiety (fullness) following a meal. There is evidence to suggest that certain specialised cells in the gut wall can identify basic carbohydrate, protein and fat in the gut, which can trigger GLP-1 secretion. The aim of this study is to investigate if GLP-1 secretion is stimulated in human volunteers by ingesting capsules of nutrients, such as basic protein and fat. We will do this by giving capsules containing nutrients and naturally-occurring substances to volunteers, with subsequent blood testing to identify any changes in blood gut hormone levels. It is hoped that this study, if successful, will permit future development of novel treatment strategies for obesity and T2DM.

Who can participate?
The study will be recruiting 180 people aged 18-65 years old including 90 healthy volunteers and 90 patients with T2DM.

What does the study involve?
Participants will be asked to fast overnight and attend the Clinical Research Facility in the morning. There are several different types of study visit – not all participants will do all visits. On most visits, the participant will have a cannula (tube) inserted into a vein and baseline blood tests will be taken. They will then be asked to take either capsules containing the active ingredient or placebo (dummy) capsules. Participants will be asked to fill out a questionnaire about hunger levels and will have blood removed from the cannula at intervals over the next 4-6 hours. Some participants will have a DXA scan to assess body composition. This requires a very low dose of radiation. Other types of study visit involve participants having to drink a sugary liquid as part of an oral glucose tolerance test or to have a meal to assess effects on hunger.

What are the possible benefits and risks of participating?
The main risk is this study is that the capsules may provoke unwanted effects. The active capsules contain basic protein, fat or components of bile – all substances which occur normally in the human gut. These substances have all be given before to humans and have been well tolerated. Insertion of a cannula and blood testing can cause minor bruising. There is also a small risk that blood testing will demonstrate conditions which were previously undiagnosed. Potential participants will have the opportunity to discuss these risks fully with investigators.

Where is the study run from?
The study is run by medical doctors and researchers based at the Cambridge Institute for Medical Research (CIMR) and Addenbrooke’s Hospital in Cambridge.

When is the study starting and how long is it expected to run for?
The study is starting in November 2012 and is likely to run until July 2015.

Who is funding the study?
The study is part of a large research collaboration called Full4Health funded by a grant from the European Commission under framework programme 7.

Who is the main contact?
Dr Claire Meek
clm70@cam.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Claire Meek

ORCID ID

Contact details

Cambridge Institute for Medical Research
Wellcome Trust MRC Building
Addenbrookes Hospital Hills Road
Cambridge
CB2 2XY
United Kingdom
-
clm70@cam.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

12443

Study information

Scientific title

To establish the effect of encapsulated nutrients on gut peptide secretion, glucose tolerance and appetite

Acronym

Study hypothesis

Gut hormones are released in response to ingested nutrients and are important in the regulation of appetite and control of insulin secretion. These hormones are released by specialised cells known as L cells, which are located in the lower part of the small intestine. Under normal conditions, ingested nutrients are subject to absorption and enzymatic degradation in more proximal parts of the intestine and therefore negligible quantities reach the L cells. By encapsulating nutrients in an acid, enzyme-resistant capsule, it may be possible to deliver nutrients to target parts of the intestine where they will come into direct contact with L cells.

This study will involve a series of randomised controlled trials which will examine the effect of giving encapsulated nutrients to healthy volunteers on gut hormone secretion and the consequent impact on insulin secretion and appetite.

More details can be found at: http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=12443

Ethics approval

Norfolk & Norwich, 25 September 2012 ref: 12/EE/0389

Study design

Randomised interventional trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Metabolic and endocrine diseases

Intervention

Each participant will receive both placebo and active treatments at different visits. Each participant will receive one capsule type at one dose per visit with an interval period of at least 24 hours between visits. Each participant will have 3-6 visits. All capsules will be taken orally.

For example:
Visit 1- Active dose at level 1
Visit 2- Placebo
Visit 3- Active dose at level 2

The active capsules contain one of the following ingredients which will be tested individually against placebo:
Glutamine – a naturally-occurring protein. Approximate doses 0.6-6g
Mono-oleoyl glycerol – found naturally in olive oil. Approximate doses 0.3-6g
Sodium taurocholate – a normal component of bile. Approximate doses 0.5-7g
The placebo capsule contains microcrystalline cellulose.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

Concentrations of gut hormones (such as GLP-1, GIP or PYY) will be measured in plasma at timepoints 0, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5 and 6 hours after capsule ingestion. The outcome will be assessed by peak hormone concentrations and area under the curve calculations.

Secondary outcome measures

1. Effect of capsules on glucose & insulin levels:
Glucose and insulin levels will be measured at timepoints 0, 1, 2, 2.5, 3, 3.5 and 4 hours following a 75g oral glucose tolerance test. The outcome will be assessed by peak concentrations of glucose and insulin, concentrations at 2, 3 and 4 hours post-ingestion and area under the curve calculations.

2. Effect of capsules on perceived hunger and satiety
Hunger and satiety will be measured using a visual analogue scale. The outcome will be measured by peak values of hunger and satiety and area under the curve calculations.

3. Effect of capsules on food intake
Food quantity ingested and speed of intake will be assessed using an ad libitum meal and universal eating monitor. The outcome will be measured by total caloric content ingested, calories ingested at timepoints 5, 10, 20 and 30 minutes after the start of the meal, and area under the curve for caloric intake.

4. Safety and tolerability of the capsules
Safety and tolerability will be assessed using a symptom diary with a severity scale. Peak severity score and area under the curve measurements will be assessed for adverse effects in comparison to placebo.

Overall trial start date

01/10/2012

Overall trial end date

01/07/2015

Reason abandoned

Eligibility

Participant inclusion criteria

Tasks 1-2
1. Healthy male or female subjects, aged 18 to 65 years.
2. BMI 18 to 45 kg/m2.
3. Willingness to attend the CRF on 4-5 occasions at approximately 12 week intervals for administration of capsules.

Tasks 3-5
1. Male or female subjects, aged 18 to 65 years with T2DM or glucose intolerance as diagnosed by a previous OGTT and /or fasting glucose level and HbA1c level.
2. BMI 18 to 45 kg/m2.
3. Willingness to attend the CRF on 4-5 occasions and take capsules three times daily for a total period of four weeks
4. Male & female participants
5. Aged 18 - 65 years

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

UK Sample Size: 180

Participant exclusion criteria

1. Age <18 or >65 years old at enrolment
2. BMI <18 or >45 kg/m2 at enrolment
3. Pregnancy or breast feeding
4. Any current medical disorder or history of disorder with potential to influence parameters measured in this study
5. Any current medical disorder or history of disorder likely to influence the ability follow the study protocol safely and effectively
6. Any current medication or history of medication likely to influence parameters measured in this study. For example, patients with T2DM should be on oral medication only and not on exogenous insulin or injectable GLP-1 mimetics
7. Current or historical drug or alcohol abuse
8. Current smoking habit
9. Any concern that a potential participant may not understand the nature or requirements of the study sufficiently to consent to participation
10. Any other circumstance or condition not covered above which would make participation unreasonable

Recruitment start date

01/10/2012

Recruitment end date

01/07/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Cambridge Institute for Medical Research
Cambridge
CB2 2XY
United Kingdom

Sponsor information

Organisation

Cambridge Institute for Medical Research (UK)

Sponsor details

Wellcome Trust MRC Building
Addenbrookes Hospital Hills Road
Cambridge
CB2 2XY
United Kingdom

Sponsor type

Research organisation

Website

http://www.cimr.cam.ac.uk/

Funders

Funder type

Government

Funder name

Seventh Framework Programme

Alternative name(s)

EC Seventh Framework Programme, European Commission Seventh Framework Programme, EU Seventh Framework Programme, European Union Seventh Framework Programme, FP7

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Belgium

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes