Investigating Optimal Propionate Delivery to the Colon Using Stable Isotope Labeling

NCT02229500 | Completed

• 1 other identifier: BB/L004259/1_SUERC_1
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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. Of the SCFAs produced by colonic fermentation of dietary fibre, propionate has the highest affinity for FFAR 2. Furthermore, propionate is an end product of bacterial metabolism, and thus, unlike acetate, does not undergo conversion to other SCFAs. Increasing colonic propionate is therefore an attractive target for appetite modulation. We have developed a novel delivery system for delivering propionate to the right site in the colon and we now wish to optimise the delivery of propionate to the colon in man using stable isotope labelling methods.

Conditions

Optimum Propionate Delivery to the Large Intestine

Keywords

Propionate; Microbiome; Dietary Fibre; Short chain fatty acids

Outcome Measures

Primary Outcomes (1)

• Time to maximal 13C appearance in breath

  The time to peak maximal excretion in breath 13C (measured in breath 13CO2) will be the primary outcome criterion

  over 24 hrs

Secondary Outcomes (1)

• Area under curve of breath 13C excretion

  over 24hrs

Other Outcomes (1)

• Effect of preparations on appetite

  0ver 8 hrs

Study Arms (3)

Control

ACTIVE COMPARATOR

Inulin control, 10g/d for 7 days. Isotope and appetite measurements on day 7

Dietary Supplement: Inulin

Delivery system 1

EXPERIMENTAL

Delivery system, 28.5% w/w propionate, 10g/d for 7 days. Isotope and appetite measurements on day 7.

Dietary Supplement: 2.5 g of propionate

Delivery system 2

EXPERIMENTAL

Delivery system, 54% w/w propionate, 10g/d for 7 days. Isotope and appetite measurements on day 7.

Dietary Supplement: 5 g of propionate

Interventions

Inulin DIETARY_SUPPLEMENT

Also known as: Beneo-Orafti HP

Control

2.5 g of propionate DIETARY_SUPPLEMENT

This system delivers approximately 2.5 g of propionate to the colon in a 10g dose.

Delivery system 1

5 g of propionate DIETARY_SUPPLEMENT

This delivers approximately 5g of propionate to the colon per 10g dose

Delivery system 2

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• overweight males (BMI 25-35 kg/m2) aged between 21 - 65

You may not qualify if:

• Weight change of \> 3kg in the preceding 2 months
• Current smokers
• Substance abuse
• Excess alcohol intake
• Pregnancy
• Diabetes
• Cardiovascular disease
• Cancer
• Gastrointestinal disease
• Kidney disease
• Liver disease
• Pancreatitis
• Use of any medication

Sponsors & Collaborators

• Scottish Universities Environmental Research Centre: lead
• Biotechnology and Biological Sciences Research Council: collaborator
• University of Glasgow: collaborator

Study Sites (1)

Glasgow Clinical Research Facility

Glasgow, Lanarkshire, G4 0SF, United Kingdom

Location

MeSH Terms

Interventions

Inulin; Propionates

Intervention Hierarchy (Ancestors)

Starch; Glucans; Biopolymers; Polymers; Macromolecular Substances; Dietary Carbohydrates; Carbohydrates; Fructans; Polysaccharides; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Douglas Morrison, PhD

  University of Glasgow

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2014
• First Posted: September 1, 2014
• Study Start: August 1, 2014
• Primary Completion: August 1, 2015
• Study Completion: December 1, 2015
• Last Updated: April 28, 2016

Record last verified: 2016-04

Locations

GB (1)