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Trial record 64 of 400 for:    PYY

RCT to Describe the Effects of Colon Delivered Acetate, Propionate and Butyrate on Satiety and Glucose Homeostasis (PRO-ESTER)

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ClinicalTrials.gov Identifier: NCT02451189
Recruitment Status : Completed
First Posted : May 21, 2015
Last Update Posted : April 28, 2016
Sponsor:
Collaborators:
NHS Greater Clyde and Glasgow
University of Glasgow
Information provided by (Responsible Party):
Dr Douglas Morrison, Scottish Universities Environmental Research Centre

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Obesity Overweight Dietary Supplement: Inulin acetate ester Dietary Supplement: Inulin propionate ester Dietary Supplement: Inulin butyrate ester Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Study Start Date : January 2015
Actual Primary Completion Date : April 2016
Actual Study Completion Date : April 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Inulin

Arm Intervention/treatment
Experimental: Inulin acetate ester
Inulin acetate ester, 10g/day for 30 days
Dietary Supplement: Inulin acetate ester
Inulin acetate ester supplementation (10g/d) for 30 days. Appetite measurements on day 15 and oral glucose tolerance test (OGTT) on day 30.

Experimental: Inulin propionate ester
Inulin propionate ester, 10g/day for 30 days
Dietary Supplement: Inulin propionate ester
Inulin propionate ester supplementation (10g/d) for 30 days. Appetite measurements on day 15 and OGTT on day 30.

Experimental: Inulin butyrate ester
Inulin butyrate ester, 10g/day for 30 days
Dietary Supplement: Inulin butyrate ester
Inulin butyrate ester supplementation (10g/d) for 30 days. Appetite measurements on day 15 and OGTT on day 30.




Primary Outcome Measures :
  1. Energy intake at ad libitum meal [ Time Frame: 8 hours ]
    Energy intake is measured at an ad libitum meal


Secondary Outcome Measures :
  1. Subjective appetite sensations [ Time Frame: 8 hours ]
    Appetite is rated on 100 mm visual analogue scales

  2. Plasma glucose and insulin [ Time Frame: 2 hours ]
    Oral glucose tolerance test: Fasting and 2h glucose and insulin concentrations following consumption of solution providing 75g glucose


Other Outcome Measures:
  1. Intestinal bacteria composition [ Time Frame: 24 hours ]
    Faecal samples will be collected to assess the impact of the NDC esters on gut bacteria composition

  2. Lipids [ Time Frame: 8 hours ]
    Serum triglycerides and cholesterol concentrations will be determined

  3. Appetite regulating gut hormones [ Time Frame: 8 hours ]
    Fasting and postprandial gut hormone concentrations will be measured

  4. Liver function test [ Time Frame: 1hour ]


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Ages Eligible for Study:   21 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male and Female
  • Healthy
  • Overweight (BMI 25-40 kg/m2)

Exclusion Criteria:

  • Weight change of > 3kg in the preceding 2 months
  • Current smokers
  • Substance abuse
  • Excess alcohol intake
  • Diabetes
  • Cardiovascular disease
  • Cancer
  • Gastrointestinal disease
  • Kidney disease
  • Liver disease
  • Pancreatitis
  • Use of any medication except contraceptive pill
  • Peri-menopausal
  • Pregnancy
  • Breastfeeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02451189


Locations
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United Kingdom
Glasgow Clinical Research Facility
Glasgow, Lanarkshire, United Kingdom, G4 0SF
Sponsors and Collaborators
Scottish Universities Environmental Research Centre
NHS Greater Clyde and Glasgow
University of Glasgow
Investigators
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Principal Investigator: Douglas Morrison, PhD Scottish Universitites Environmental Research Centre

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Responsible Party: Dr Douglas Morrison, Senior Lecturer, Scottish Universities Environmental Research Centre
ClinicalTrials.gov Identifier: NCT02451189     History of Changes
Other Study ID Numbers: PRO-ESTER STUDY
First Posted: May 21, 2015    Key Record Dates
Last Update Posted: April 28, 2016
Last Verified: April 2016

Keywords provided by Dr Douglas Morrison, Scottish Universities Environmental Research Centre:
Obesity
Weight maintenance
Appetite
Energy intake
Dietary fibre
Short-chain fatty acids
Fermentation
Overweight

Additional relevant MeSH terms:
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Overweight
Body Weight
Signs and Symptoms