Exogenous Ketosis in a Fed and a Fasted State

NCT06320522 | Recruiting

• 1 other identifier: R82053/RE002
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The kinetics of circulating βHB following ingestion of the ketone monoester are dependent on several variables that determine the balance between appearance into, and disappearance from, the bloodstream. These dynamics have been well characterised in fasted humans but in the real world the ketone monoester is likely to be ingested in a fed state, pertinently within athletic spheres consumption would proceed a substantial high-carbohydrate meal. Within this, it is unclear how metabolism under exogenous ketosis might be affected in a fed versus fasted state. This four-arm crossover study looks to characterise the relationship between feeding status, βHB pharmacokinetics, and resting metabolism. As exogenous ketosis is known to reduce circulating glucose levels, this study will also explored if hepatic metabolism - for example, de novo lipogenesis - might consequently be altered, with implications for metabolic disease states such as Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and type II diabetes. Participants will be asked to consume either the ketone monoester drink or a placebo drink when fasted and when having previously consumed a meal.

Conditions

Ketosis; Exogenous Ketosis

Keywords

Exogenous Ketosis; Hepatic; Metabolism; Postprandial; Postabsorptive

Outcome Measures

Primary Outcomes (3)

• Plasma β-hydroxybutyrate (βHB) kinetics

  Changes in concentration of plasma βHB (mM) over the post-drink time period

  7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)

• Plasma glucose kinetics

  Changes in concentration of plasma glucose (mM) over the post-drink time period

  7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)

• Postprandial de novo lipogenesis (DNL)

  DNL in the fed visits - quantified as the incorporation of deuterium from heavy water into newly synthesised palmitate within very low-density lipoprotein-triglyceride (VLDL-TG)

  7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)

Secondary Outcomes (8)

• Plasma biochemistry

  7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)

• Very low-density lipoprotein-triglyceride (VLDL-TG) fatty acid composition

  7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)

• Breath acetone

  7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)

• Urine volume

  7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)

• Urine composition

  7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)

Study Arms (4)

Fed - Ketone Monoester

ACTIVE COMPARATOR

Ketone monoester drink (573 mg∙kg-1 body weight) provided 1 hour after a 2 g∙kg-1 bodyweight of carbohydrate mixed nutrient breakfast meal

Dietary Supplement: Ketone Monoester

Fed - Placebo

PLACEBO COMPARATOR

Placebo drink provided 1 hour after a 2 g∙kg-1 bodyweight of carbohydrate mixed nutrient breakfast meal

Dietary Supplement: Placebo

Fasted - Ketone Monoester

ACTIVE COMPARATOR

Ketone monoester drink (573 mg∙kg-1 body weight) provided whilst fasted

Dietary Supplement: Ketone Monoester

Fasted - Placebo

PLACEBO COMPARATOR

Placebo drink provided whilst fasted

Dietary Supplement: Placebo

Interventions

Ketone Monoester DIETARY_SUPPLEMENT

Commercial dietary supplement intended raise blood ketone body levels

Also known as: deltaG, (R)-3-hydroxybutyl (R)-3-hydroxybutyrate

Fasted - Ketone Monoester; Fed - Ketone Monoester

Placebo DIETARY_SUPPLEMENT

Placebo drink (2mM sucrose octaacetate) taste and volume matched to the ketone monoester drinks

Also known as: Sucrose Octaacetate

Fasted - Placebo; Fed - Placebo

Eligibility Criteria

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

You may qualify if:

• Habitually consuming a mixed macronutrient diet
• Fluent in English, no communication impairments, willing \& able to give informed consent for participation in the study
• Not currently taking any medication (except the contraceptive pill)
• No food allergies incompatible with the supplement drinks or with the standardised breakfast where a suitable substitution cannot be practically made
• Female-only - on contraception (pill/implant/coil/etc); not pregnant/currently breastfeeding; pre-menopausal; not undertaking hormone replacement therapy (HRT)
• In the investigator's opinion - able and willing to comply with all study requirements

You may not qualify if:

• Significant cardiovascular disease or metabolic risk factors, or family history of it, on health screening questionnaire
• Food allergies incompatible with the supplement drinks or standardised breakfast
• Having been on a ketogenic diet in the 6 months prior to enrolment
• Any other significant disease or disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study/the participant's ability to participate in the study
• Concurrently a participant in any other dietary intervention study/have taken part in one within 1 month of enrolment
• Diabetic
• Pregnant or breastfeeding
• Known history of moderate-to-severe motion sickness

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Oxford Centre for Diabetes, Endocrinology, and Metabolism (OCDEM)

Oxford, Oxfordshire, OX3 7LE, United Kingdom

RECRUITING

MeSH Terms

Conditions

Ketosis

Interventions

rVSV-deltaG-spike COVID-19 vaccine; (R)-3-hydroxybutyl (R)-3-hydroxybutyrate; sucrose octaacetate

Condition Hierarchy (Ancestors)

Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Leanne Hodson, PhD

CONTACT

01865 857224; leanne.hodson@ocdem.ox.ac.uk

Study Design

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

Study Record Dates

• First Submitted: March 5, 2024
• First Posted: March 20, 2024
• Study Start: February 15, 2023
• Primary Completion: May 1, 2024
• Study Completion: May 1, 2024
• Last Updated: March 20, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)