Clinical trial NCT04093453: The Acute Effect of Propionate on Energy Homeostasis
Official title: The Acute Effect of Propionate on Energy Homeostasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Keywords: Short Chain Fatty Acids
Propionate
Energy Expenditure
Lipid Oxidation
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2019-09-18
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This protocol consisted of three individual trials.
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Changes in Resting Energy Expenditure
timeFrame: 6 hours
measure: Changes in Resting Lipid Oxidation
timeFrame: 6 hours
measure: Changes in Energy Expenditure During Exercise
timeFrame: 240 minutes
measure: Changes in Lipid Oxidation During Exercise
timeFrame: 240 minutes
measure: Changes in Energy Expenditure Post-prandially
timeFrame: 300 minutes
measure: Changes in Lipid Oxidation Post-prandially
timeFrame: 300 minutes
measure: Changes in Glucose Concentrations Post-prandially
timeFrame: 300 minutes
measure: Changes in Glucose Concentrations During Exercise
timeFrame: 240 minutes
measure: Changes in Subjective Thirst Post-prandially Using a Visual Analog Scale (100 mm).
timeFrame: 300 minutes
measure: Changes in Subjective Thirst During Exercise With Visual Analog Scales (100 mm)
timeFrame: 240 minutes
measure: Changes in Subjective Nausea During Exercise With Visual Analog Scales (100 mm)
timeFrame: 240 minutes
measure: Changes in Subjective Hunger During Exercise With Visual Analog Scales (100 mm)
timeFrame: 240 minutes
Secondary outcomes:
measure: Changes in GLP-1 Concentration
timeFrame: 300 minutes
measure: Changes in Insulin Concentration
timeFrame: 360 minutes
measure: Changes in Glucose Concentration
timeFrame: 360 minutes
measure: Changes in Free Fatty Acid Concentration
timeFrame: 360 minutes
measure: Changes in Subjective Nausea With Visual Analog Scales (100 mm)
timeFrame: 360 minutes
measure: Changes in Subjective Hunger With Visual Analog Scales (100 mm)
timeFrame: 360 minutes
measure: Changes in Subjective Thirst Using Visual Analog Scales (100 mm)
timeFrame: 360 minutes
measure: Changes in Insulin Concentration
timeFrame: 240 minutes
measure: Changes in Insulin Concentration
timeFrame: 300 minutes
measure: Changes in Subjective Nausea Between Sodium Propionate and Sodium Chloride Post-prandially
timeFrame: 300 minutes
measure: Changes in Subjective Hunger Between Sodium Propionate and Sodium Chloride Post-prandially With Visual Analog Scales (100 mm)
timeFrame: 300 minutes
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial Clinical Research Facility
Study officials:
affiliation: Imperial College London
name: Edward Chambers, PhD
role: STUDY_DIRECTOR
affiliation: Imperial College London
name: Gary Frost, Professor
role: PRINCIPAL_INVESTIGATOR
References: