ObesityPRO-ESTERNCT02451189
RCT to Describe the Effects of Colon Delivered Acetate, Propionate and Butyrate on Satiety and Glucose Homeostasis
A study testing Inulin acetate ester, Inulin propionate ester and Inulin butyrate ester in people with Obesity and Overweight, run by Scottish Universities Environmental Research Centre at 1 site in United Kingdom.
Trial summary
Obesity, with its associated co-morbidities, is a major public health challenge. It is estimated that by 2050, 60% of men and 50% of women will be clinically obese. Obesity is associated with increased risk of developing diabetes, cardiovascular disease, and certain cancers. Read more about this study
- Who is it for?
- Ages 21 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity, Overweight
- What is being tested?
- Inulin acetate ester, Inulin propionate ester and Inulin butyrate ester
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2015to Apr 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male and Female
- Healthy
- Overweight (BMI 25-40 kg/m2)
Who cannot join
- Weight change of > 3kg in the preceding 2 months
- Current smokers
- Substance abuse
- Excess alcohol intake
- Diabetes
- Cardiovascular disease
Show all 15Show fewer
- Cancer
- Gastrointestinal disease
- Kidney disease
- Liver disease
- Pancreatitis
- Use of any medication except contraceptive pill
- Peri-menopausal
- Pregnancy
- Breastfeeding
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Glasgow Clinical Research Facility
Glasgow, Lanarkshire, G4 0SF
About this study
Obesity, with its associated co-morbidities, is a major public health challenge. It is estimated that by 2050, 60% of men and 50% of women will be clinically obese. Obesity is associated with increased risk of developing diabetes, cardiovascular disease, and certain cancers. The increasing epidemic of obesity has necessitated the study of the complex mechanisms underlying energy homeostasis. Food intake, energy balance and body weight are tightly regulated by the hypothalamus, brainstem and reward circuits, on the basis both of cognitive inputs and of diverse humoral and neuronal signals of nutritional status. Several gut hormones, including glucagon-like peptide-1 (GLP-1) and peptide YY3-36 (PYY), have been shown to play an important role in regulating short-term food intake. Peripheral administration of PYY or GLP-1 enhances satiety and reduces food intake in animals and man. PYY, GLP-1 along with a host of other hormones are produced by the gut in response to nutrient availability in different regions of the gut and provide an exquisite mechanism of nutrient sensing in response to dietary intake. These hormones therefore represent potential targets in the development of novel anti-obesity treatments. A novel and attractive strategy to induce appetite regulation is the enrichment of foods with components that stimulate the release of GLP-1 and PYY. The short chain fatty acids (SCFA) produced by microbial fermentation of dietary fibre in the colon have been shown to stimulate the release of PYY and GLP-1 from rodent enteroendocrine L cells, via stimulation of the G-protein coupled free fatty acid receptors (FFAR) on colonic L cells. However, it is not known whether the three SCFA, acetate, butyrate and propionate, differentially affect appetite and glucose control. The aim of this study is to compare the effects of increased colonic delivery of acetate, butyrate and propionate on appetite and glucose control in overweight men in a randomised crossover study.
Read the detailed description
The role of SCFA in appetite regulation: SCFA have been shown to stimulate PYY and GLP-1 production in animal models and dietary fibre, of which SCFA are the major end products, induce appetite regulation in humans. However the evidence underpinning which dietary fibres induce appetite regulation in humans is very weak because of the difficulty in controlling studies with very high fibre intake. In a recent project funded under the BBSRC DRINC initiative (BB/H004815/1), the investigators have the first direct evidence that SCFA can directly regulate appetite in humans. Prior to this study, in order to achieve production of SCFA to a level, which is high enough to induce appetite-regulating effects, very large amounts of dietary fibre (>25 g/d and up to 40 g/d) are required, and compliance with high fibre diets is poor due to gastrointestinal side effects. Furthermore, supplementing diets with mixed high fibre does not predictably or reliably increase colonic SCFA production or circulating levels of SCFA in all human populations because of the variability in gut microbial activity. Finally, orally administered SCFAs are not palatable and are rapidly absorbed in the small intestine where L cells are sparse. In our studies to date we have focussed on the SCFA propionate because it has the highest affinity for the receptors and is an end product of metabolism in the microbiota and therefore seems the obvious target to manipulate to investigate the effects of SCFA on appetite regulation. To overcome the unpalatably high levels of fermentable dietary fibre needed to significantly increase colonic propionate levels, and the unpredictability in the production of the resulting SCFAs, the investigators have developed and tested a novel delivery system targeting the release of gram quantities of propionate in the proximal colon. It is estimated that the delivery system may lead to a 2-8 fold increase in colonic propionate, a level very difficult to achieve through feeding a mixed fermentable fibre diet. This level of propionate production might have been observed in ancestral diets and in parts of rural Africa where dietary fibre intake is very high. Previous work, conducted by the investigators, has also demonstrated that delivery system increases plasma propionate levels, reduces food intake in acute studies of appetite, and in a longer term study (24 weeks), positive effects on food intake, body composition, glucose homeostasis, circulating lipids, cholesterol and liver function, liver and visceral fat and weight management were observed. However, at present it is not known if acetate, propionate and butyrate exert similar effects on appetite and glucose metabolism. Therefore in this study we wish to compare the the effects of targeted delivery of acetate, propionate and butyrate to the proximal colon on appetite and glucose homeostasis in overweight men.
- Conditions
- Obesity, Overweight
- Being tested
- Inulin acetate ester, Inulin propionate ester, Inulin butyrate ester
- Keywords
- Obesity, Weight maintenance, Appetite, Energy intake, Dietary fibre, Short-chain fatty acids, Fermentation, Overweight
- Medical subject headings
- Obesity, Overweight
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inulin acetate esterDietary supplement
Inulin acetate ester supplementation (10g/d) for 30 days. Appetite measurements on day 15 and oral glucose tolerance test (OGTT) on day 30.
Inulin propionate esterDietary supplement
Inulin propionate ester supplementation (10g/d) for 30 days. Appetite measurements on day 15 and OGTT on day 30.
Inulin butyrate esterDietary supplement
Inulin butyrate ester supplementation (10g/d) for 30 days. Appetite measurements on day 15 and OGTT on day 30.
| Study group | Role | What they receive |
|---|---|---|
| Inulin acetate ester | Experimental | Inulin acetate ester, 10g/day for 30 days Receives: Dietary Supplement: Inulin acetate ester |
| Inulin propionate ester | Experimental | Inulin propionate ester, 10g/day for 30 days Receives: Dietary Supplement: Inulin propionate ester |
| Inulin butyrate ester | Experimental | Inulin butyrate ester, 10g/day for 30 days Receives: Dietary Supplement: Inulin butyrate ester |
What is being measured
The primary outcome is the main question the study is designed to answer.
Energy intake at ad libitum meal
Energy intake is measured at an ad libitum meal
Measured: 8 hours
Secondary outcomes (2)
Subjective appetite sensations
Appetite is rated on 100 mm visual analogue scales
Measured: 8 hours
Plasma glucose and insulin
Oral glucose tolerance test: Fasting and 2h glucose and insulin concentrations following consumption of solution providing 75g glucose
Measured: 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2015 (estimated)
- Study startJan 2015
- Primary completionApr 2016
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Scottish Universities Environmental Research Centre
- Sponsor type
- University, hospital or other
- Collaborators
- NHS Greater Clyde and Glasgow, University of Glasgow
- Responsible party
- Principal investigator, Dr Douglas Morrison, Scottish Universities Environmental Research Centre
- Investigators
- Douglas Morrison, PhD, Principal investigator, Scottish Universitites Environmental Research Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02451189
- Sponsor's protocol ID
- PRO-ESTER STUDY
- Acronym
- PRO-ESTER
- Status last verified
- Apr 2016
- First submitted
- 19 May 2015
- Last updated
- 28 Apr 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RCT to Describe the Effects of Colon Delivered Acetate, Propionate and Butyrate on Satiety and Glucose Homeostasis
- ClinicalTrials.gov ID
- NCT02451189
- Acronym / sponsor ID
- PRO-ESTER / PRO-ESTER STUDY
- Conditions
- Obesity, Overweight
- Keywords
- Obesity, Weight maintenance, Appetite, Energy intake, Dietary fibre, Short-chain fatty acids, Fermentation, Overweight
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Scottish Universities Environmental Research CentreUniversity, hospital or other
- Collaborators
- NHS Greater Clyde and Glasgow, University of Glasgow
- Study start
- Jan 2015
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 21 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Obesity, with its associated co-morbidities, is a major public health challenge. It is estimated that by 2050, 60% of men and 50% of women will be clinically obese. Obesity is associated with increased risk of developing diabetes, cardiovascular disease, and certain cancers. The increasing epidemic of obesity has necessitated the study of the complex mechanisms underlying energy homeostasis. Food intake, energy balance and body weight are tightly regulated by the hypothalamus, brainstem and reward circuits, on the basis both of cognitive inputs and of diverse humoral and neuronal signals of nutritional status. Several gut hormones, including glucagon-like peptide-1 (GLP-1) and peptide YY3-36 (PYY), have been shown to play an important role in regulating short-term food intake. Peripheral administration of PYY or GLP-1 enhances satiety and reduces food intake in animals and man. PYY, GLP-1 along with a host of other hormones are produced by the gut in response to nutrient availability in different regions of the gut and provide an exquisite mechanism of nutrient sensing in response to dietary intake. These hormones therefore represent potential targets in the development of novel anti-obesity treatments. A novel and attractive strategy to induce appetite regulation is the enrichment of foods with components that stimulate the release of GLP-1 and PYY. The short chain fatty acids (SCFA) produced by microbial fermentation of dietary fibre in the colon have been shown to stimulate the release of PYY and GLP-1 from rodent enteroendocrine L cells, via stimulation of the G-protein coupled free fatty acid receptors (FFAR) on colonic L cells. However, it is not known whether the three SCFA, acetate, butyrate and propionate, differentially affect appetite and glucose control. The aim of this study is to compare the effects of increased colonic delivery of acetate, butyrate and propionate on appetite and glucose control in overweight men in a randomised crossover study.
Detailed description
The role of SCFA in appetite regulation: SCFA have been shown to stimulate PYY and GLP-1 production in animal models and dietary fibre, of which SCFA are the major end products, induce appetite regulation in humans. However the evidence underpinning which dietary fibres induce appetite regulation in humans is very weak because of the difficulty in controlling studies with very high fibre intake. In a recent project funded under the BBSRC DRINC initiative (BB/H004815/1), the investigators have the first direct evidence that SCFA can directly regulate appetite in humans. Prior to this study, in order to achieve production of SCFA to a level, which is high enough to induce appetite-regulating effects, very large amounts of dietary fibre (>25 g/d and up to 40 g/d) are required, and compliance with high fibre diets is poor due to gastrointestinal side effects. Furthermore, supplementing diets with mixed high fibre does not predictably or reliably increase colonic SCFA production or circulating levels of SCFA in all human populations because of the variability in gut microbial activity. Finally, orally administered SCFAs are not palatable and are rapidly absorbed in the small intestine where L cells are sparse. In our studies to date we have focussed on the SCFA propionate because it has the highest affinity for the receptors and is an end product of metabolism in the microbiota and therefore seems the obvious target to manipulate to investigate the effects of SCFA on appetite regulation. To overcome the unpalatably high levels of fermentable dietary fibre needed to significantly increase colonic propionate levels, and the unpredictability in the production of the resulting SCFAs, the investigators have developed and tested a novel delivery system targeting the release of gram quantities of propionate in the proximal colon. It is estimated that the delivery system may lead to a 2-8 fold increase in colonic propionate, a level very difficult to achieve through feeding a mixed fermentable fibre diet. This level of propionate production might have been observed in ancestral diets and in parts of rural Africa where dietary fibre intake is very high. Previous work, conducted by the investigators, has also demonstrated that delivery system increases plasma propionate levels, reduces food intake in acute studies of appetite, and in a longer term study (24 weeks), positive effects on food intake, body composition, glucose homeostasis, circulating lipids, cholesterol and liver function, liver and visceral fat and weight management were observed. However, at present it is not known if acetate, propionate and butyrate exert similar effects on appetite and glucose metabolism. Therefore in this study we wish to compare the the effects of targeted delivery of acetate, propionate and butyrate to the proximal colon on appetite and glucose homeostasis in overweight men.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Inulin acetate ester | Experimental | Dietary Supplement: Inulin acetate esterInulin acetate ester, 10g/day for 30 days |
| Inulin propionate ester | Experimental | Dietary Supplement: Inulin propionate esterInulin propionate ester, 10g/day for 30 days |
| Inulin butyrate ester | Experimental | Dietary Supplement: Inulin butyrate esterInulin butyrate ester, 10g/day for 30 days |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Male and Female
- Healthy
- Overweight (BMI 25-40 kg/m2)
Key exclusion criteria (15 listed)
- Weight change of > 3kg in the preceding 2 months
- Current smokers
- Substance abuse
- Excess alcohol intake
- Diabetes
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Inulin acetate esterInulin acetate ester supplementation (10g/d) for 30 days. Appetite measurements on day 15 and oral glucose tolerance test (OGTT) on day 30. | Dietary supplement | Inulin acetate ester |
| Inulin propionate esterInulin propionate ester supplementation (10g/d) for 30 days. Appetite measurements on day 15 and OGTT on day 30. | Dietary supplement | Inulin propionate ester |
| Inulin butyrate esterInulin butyrate ester supplementation (10g/d) for 30 days. Appetite measurements on day 15 and OGTT on day 30. | Dietary supplement | Inulin butyrate ester |
Primary outcome
Energy intake at ad libitum meal
Time frame: 8 hours
Energy intake is measured at an ad libitum meal
2 secondary outcomes
Subjective appetite sensations
Time frame: 8 hours
Plasma glucose and insulin
Time frame: 2 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Douglas Morrison, PhD principal investigator
Scottish Universitites Environmental Research Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Inulin acetate ester, Inulin propionate ester and Inulin butyrate ester in people with Obesity and Overweight, run by Scottish Universities Environmental Research Centre at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Energy intake at ad libitum meal (time frame: 8 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2016.