Propionate and Energy Homeostasis (PROEM)

The Acute Effect of Propionate on Energy Homeostasis

The research project aims to examine the effect of a dietary supplement called propionate on how the human body in healthy adults aged (18- 65 years) responds to during fasting, exercise and following a liquid mixed meal test and how that would affect energy homeostasis and substrate oxidation.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Other: Placebo (Sodium Chloride); Other: Exercise; Dietary supplement: Sodium Propionate

Detailed Description

Dietary fibres have long been recognised for their important role in a healthy diet due to their negative association with, and even management of, chronic diseases such as obesity, diabetes, metabolic syndrome, cardiovascular disease and inflammatory-bowel disease among others.Emerging evidence has suggested that these benefits could largely be attributed to short chain fatty acids (SCFA) (acetate, propionate and butyrate), the main by-products of fibre fermentation in the gut. Previous research has demonstrated that a long-term elevation in the SCFA propionate significantly reduced body weight gain in overweight adults and reduced liver fat storage.

The current project will examine potential mechanisms for the positive effect of propionate on energy homeostasis and metabolic profile.The effects of propionate on circulating glucose, insulin, gut hormones and lipid levels at rest, following moderate-intensity exercise and mixed meal tolerance test will be examined.

To acutely increase propionate absorption from the gut the present project will use a simple nutritional supplement: sodium propionate in a hydroxypropylmethyl cellulose (HPMC) capsule. This capsule is coated with an enteric film which prevents gastric digestion until the capsule reaches the intestine. This nutritional supplement has been used in human volunteers in a previously approved ethics application (12/LO/1769: Oral propionate and glucose homeostasis). A 5g acute dose of sodium propionate had previously been tested and reported no adverse effects . The MHRA have confirmed that encapsulated sodium propionate is not classed as an investigative medicinal product.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W12 0HS
    • Imperial Clinical Research Facility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteers (body mass index (BMI) of 18-35 kg/m2)
• Age between 18-65 years (inclusive)

Exclusion Criteria:

• Weight change of ≥ 3kg in the preceding 2 months
• Current smokers
• Substance abuse
• Excess alcohol intake
• Pregnancy
• Diabetes
• Cardiovascular disease
• Cancer
• Gastrointestinal disease e.g. inflammatory bowel disease or irritable bowel syndrome
• Kidney disease
• Liver disease
• Pancreatitis
• Started new medication within the last 3 months likely to interfere with energy metabolism, appetite regulation and hormonal balance, including: anti-inflammatory drugs or steroids, antibiotics, androgens, phenytoin, erythromycin or thyroid hormones.
• Involved in current research or have recently been involved in any research prior to recruitment in the past 12 weeks.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo + Fasting; Sodium Chloride tested in a fasting state. Participants will be fasting for duration of study visit (360 minutes).	Other: Placebo (Sodium Chloride); Participant receive Placebo (Sodium Chloride)
Placebo Comparator: Placebo + Exercise; Sodium Chloride tested in an exercise state. Participants will have the placebo then exercise will be performed at 40% of maximal aerobic capacity for one hour.	Other: Placebo (Sodium Chloride); Participant receive Placebo (Sodium Chloride); Other: Exercise; 1 hour exercise
Placebo Comparator: Placebo + Post-prandial; Sodium Chloride tested in a post-prandial state. Participants will have the placebo then a mixed liquid meal test is given.	Other: Placebo (Sodium Chloride); Participant receive Placebo (Sodium Chloride)
Experimental: Propionate and Fasting; Sodium Propionate tested in a fasting state. Participants will be fasting for duration of study visit (360 minutes).	Dietary supplement: Sodium Propionate; Participant receive Sodium Propionate
Experimental: Propionate and Exercise; Sodium Propionate tested in an exercise state. Participants will have the sodium propionate then exercise will be performed at 40% of maximal aerobic capacity for one hour.	Other: Exercise; 1 hour exercise; Dietary supplement: Sodium Propionate; Participant receive Sodium Propionate
Experimental: Propionate and Post-prandial; Sodium Propionate tested in a post-prandial state. Participants will have the sodium propionate then a mixed liquid meal test is given.	Dietary supplement: Sodium Propionate; Participant receive Sodium Propionate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Resting Energy Expenditure	Changes in Resting Energy Expenditure between sodium propionate and sodium chloride (control).	6 hours
Changes in Resting Lipid Oxidation	Changes in Resting Lipid Oxidation between sodium propionate and sodium chloride (control).	6 hours
Changes in Energy Expenditure during Exercise	Changes in Energy Expenditure between sodium propionate and sodium chloride (control) during exercise.	240 minutes
Changes in Lipid Oxidation during Exercise	Changes in Lipid Oxidation between sodium propionate and sodium chloride (control) during exercise.	240 minutes
Changes in Energy Expenditure post-prandially	Changes in Energy Expenditure between sodium propionate and sodium chloride (control) post-prandially.	300 minutes
Changes in Lipid Oxidation post-prandially	Changes in Lipid Oxidation between sodium propionate and sodium chloride (control) post-prandially.	300 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in GLP-1 Concentration	Changes in GLP-1 concentrations between sodium propionate and sodium chloride (control) during fasting, exercise and post-prandially.	360, 240 and 300 minutes
Changes in Insulin Concentration	Changes in insulin concentrations between sodium propionate and sodium chloride (control) during fasting, exercise and post-prandially.	360, 240 and 300 minutes
Changes in glucose concentration	Changes in glucose concentrations between sodium propionate and sodium chloride (control) during fasting, exercise and post-prandially.	360, 240 and 300 minutes
Changes in free fatty acid concentration	Changes in free fatty acid concentrations between sodium propionate and sodium chloride (control) during fasting, exercise and post-prandially.	360, 240 and 300 minutes
Changes in subjective nausea	Changes in subjective nausea between sodium propionate and sodium chloride (control) during fasting, exercise and post-prandially.	360, 240 and 300 minutes
Changes in subjective hunger	Changes in subjective hunger between sodium propionate and sodium chloride (control) during fasting, exercise and post-prandially.	360, 240 and 300 minutes
Changes in subjective thirst	Changes in subjective thirst between sodium propionate and sodium chloride (control) during fasting, exercise and post-prandially.	360, 240 and 300 minutes

Collaborators and Investigators

• Sponsor: Imperial College London
• Investigators: Study Director: Edward Chambers, PhD, Imperial College London; Principal Investigator: Gary Frost, Professor, Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2018
• Primary Completion (Actual): August 7, 2019
• Study Completion (Actual): August 7, 2019

Study Registration Dates

• First Submitted: August 5, 2019
• First Submitted That Met QC Criteria: September 16, 2019
• First Posted (Actual): September 18, 2019

Study Record Updates

• Last Update Posted (Actual): October 14, 2019
• Last Update Submitted That Met QC Criteria: October 11, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Energy Expenditure; Short Chain Fatty Acids; Propionate; Lipid Oxidation
• Other Study ID Numbers: 18hh4373

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There is not a plan to make IPD available

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No