The Acute Effect of Propionate on Energy Homeostasis

Not Applicable

Completed

• Conditions: Obesity
• Interventions: Other: Placebo (Sodium Chloride); Dietary Supplement: Sodium Propionate; Other: Exercise

• Registration Number: NCT04093453
• Lead Sponsor: Imperial College London

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2018-02-12
• Study First Submitted: 2019-08-05
• Primary Completion: 2019-08-07
• Study Completion: 2019-08-07
• Study First Submitted QC: 2019-09-16
• Study First Posted: 2019-09-18
• Results First Submitted: 2021-02-25
• Status Verified: 2024-03
• Results First Submitted QC: 2024-03-22
• Last Update Submitted: 2024-03-22
• Results First Posted: 2024-08-23
• Last Update Posted: 2024-08-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 53

Inclusion Criteria

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo + Fasting	Placebo (Sodium Chloride)	Sodium Chloride tested in a fasting state. Participants will be fasting for duration of study visit (360 minutes).
Propionate and Fasting	Sodium Propionate	Sodium Propionate tested in a fasting state. Participants will be fasting for duration of study visit (360 minutes).
Placebo + Exercise	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.
Propionate and Exercise	Sodium Propionate	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.
Placebo + Exercise	Placebo (Sodium Chloride)	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.
Propionate and Post-prandial	Sodium Propionate	Sodium Propionate tested in a post-prandial state. Participants will have the sodium propionate then a mixed liquid meal test is given.
Propionate and Exercise	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.
Placebo + Post-prandial	Placebo (Sodium Chloride)	Sodium Chloride tested in a post-prandial state. Participants will have the placebo then a mixed liquid meal test is given.

Primary Outcome Measures

Name	Time	Method
Changes in Energy Expenditure During Exercise	240 minutes	Changes in Energy Expenditure between sodium propionate and sodium chloride (control) during exercise.
Changes in Resting Energy Expenditure	6 hours	Changes in Resting Energy Expenditure between sodium propionate and sodium chloride (control).
Changes in Energy Expenditure Post-prandially	300 minutes	Changes in Energy Expenditure between sodium propionate and sodium chloride (control) post-prandially.
Changes in Glucose Concentrations During Exercise	240 minutes	Changes in glucose concentrations between sodium propionate and sodium chloride (control) during exercise.
Changes in Subjective Thirst Post-prandially Using a Visual Analog Scale (100 mm).	300 minutes	Changes in subjective thirst between sodium propionate and sodium chloride (control) post-prandially. Volunteers completed the visual analog scale using a pen (Biro, black) with scales printed (Sharp MX-7580N ) on paper (A4, white). Visual analog scales were 100 mm in length. Minimum (0 mm) mean low subjective thirst. High (100 mm) mean high subjective thirst.
Changes in Subjective Nausea During Exercise With Visual Analog Scales (100 mm)	240 minutes	Changes in subjective nausea between sodium propionate and sodium chloride (control) during exercise. Volunteers completed the visual analog scale using a pen (Biro, black) with scales printed (Sharp MX-7580N ) on paper (A4, white). Visual analog scales were 100 mm in length. Minimum (0 mm) mean low subjective nausea. High (100 mm) mean high subjective nausea.
Changes in Subjective Hunger During Exercise With Visual Analog Scales (100 mm)	240 minutes	Changes in subjective hunger between sodium propionate and sodium chloride (control) during exercise. Volunteers completed the visual analog scale using a pen (Biro, black) with scales printed (Sharp MX-7580N ) on paper (A4, white). Visual analog scales were 100 mm in length. Minimum (0 mm) mean low subjective hunger. High (100 mm) mean high subjective hunger.
Changes in Resting Lipid Oxidation	6 hours	Changes in Resting Lipid Oxidation between sodium propionate and sodium chloride (control).
Changes in Lipid Oxidation During Exercise	240 minutes	Changes in Lipid Oxidation between sodium propionate and sodium chloride (control) during exercise.
Changes in Lipid Oxidation Post-prandially	300 minutes	Changes in Lipid Oxidation between sodium propionate and sodium chloride (control) post-prandially.
Changes in Glucose Concentrations Post-prandially	300 minutes	Changes in glucose concentrations between sodium propionate and sodium chloride (control) post-prandially.
Changes in Subjective Thirst During Exercise With Visual Analog Scales (100 mm)	240 minutes	Changes in subjective thirst between sodium propionate and sodium chloride (control) during exercise. Volunteers completed the visual analog scale using a pen (Biro, black) with scales printed (Sharp MX-7580N ) on paper (A4, white). Visual analog scales were 100 mm in length. Minimum (0 mm) mean low subjective thirst. High (100 mm) mean high subjective thirst.

Secondary Outcome Measures

Name	Time	Method
Changes in Insulin Concentration	300 minutes	Changes in insulin concentrations between sodium propionate and sodium chloride (control) post-prandially.
Changes in Glucose Concentration	360 minutes	Changes in glucose concentrations between sodium propionate and sodium chloride (control) during fasting
Changes in GLP-1 Concentration	300 minutes	Changes in GLP-1 concentrations between sodium propionate and sodium chloride (control) post-prandially.
Changes in Free Fatty Acid Concentration	360 minutes	Changes in free fatty acid concentrations between sodium propionate and sodium chloride (control) during fasting
Changes in Subjective Hunger Between Sodium Propionate and Sodium Chloride Post-prandially With Visual Analog Scales (100 mm)	300 minutes	Changes in subjective hunger between sodium propionate and sodium chloride (control) post-prandially. Volunteers completed the visual analog scale using a pen (Biro, black) with scales printed (Sharp MX-7580N ) on paper (A4, white). Visual analog scales were 100 mm in length. Minimum (0 mm) mean low subjective hunger. High (100 mm) mean high subjective hunger.
Changes in Subjective Nausea With Visual Analog Scales (100 mm)	360 minutes	Changes in subjective nausea between sodium propionate and sodium chloride (control) during fasting. Volunteers completed the visual analog scale using a pen (Biro, black) with scales printed (Sharp MX-7580N ) on paper (A4, white). Visual analog scales were 100 mm in length. Minimum (0 mm) mean low subjective nausea. High (100 mm) mean high subjective nausea.
Changes in Subjective Thirst Using Visual Analog Scales (100 mm)	360 minutes	Changes in subjective thirst between sodium propionate and sodium chloride (control) during fasting. Volunteers completed the visual analog scale using a pen (Biro, black) with scales printed (Sharp MX-7580N ) on paper (A4, white). Visual analog scales were 100 mm in length. Minimum (0 mm) mean low subjective thirst. High (100 mm) mean high subjective thirst.
Changes in Subjective Hunger With Visual Analog Scales (100 mm)	360 minutes	Changes in subjective hunger between sodium propionate and sodium chloride (control) during fasting. Volunteers completed the visual analog scale using a pen (Biro, black) with scales printed (Sharp MX-7580N ) on paper (A4, white). Visual analog scales were 100 mm in length. Minimum (0 mm) mean low subjective hunger. High (100 mm) mean high subjective hunger.
Changes in Subjective Nausea Between Sodium Propionate and Sodium Chloride Post-prandially	300 minutes	Changes in subjective nausea between sodium propionate and sodium chloride (control) post-prandially.

Trial Locations

Locations (1)

Imperial Clinical Research Facility; 🇬🇧 London, United Kingdom