KetosisNCT06320522
Exogenous Ketosis in a Fed and a Fasted State
A study testing Ketone Monoester in people with Ketosis and Exogenous Ketosis, run by University of Oxford at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Ketosis, Exogenous Ketosis
- What is being tested?
- Ketone Monoester
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 15 Feb 2023to 15 Jan 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Oxford Centre for Diabetes, Endocrinology, and Metabolism (OCDEM)
Oxford, Oxfordshire, OX3 7LE
About this study
Official title: Characterizing the Influence of Exogenous Ketosis on Circulating and Hepatic Metabolism in a Postprandial and Postabsorptive State in Adults Free From Metabolic Disease
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.
Read more
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.
Read the detailed description
Adults free from metabolic disease will be recruited for this randomised-counterbalanced crossover study. Participants will attend four study visits.
Participants will consume a prescribed isocaloric high-carbohydrate diet for two days prior to each visit to standardise dietary intake.
For two of these visits participants will remain 'fasted' throughout, and for the two 'fed' visits they will consume a mixed-nutrient breakfast meal. The breakfast for the 'fed' visits will provide 2g∙kg-1 bodyweight of carbohydrate.
Heavy water (D2O) will be consumed the evening preceding, and during, each fed study visit to achieve ~0.4% plasma enrichment, in order to quantify the contribution of hepatic de novo lipogenesis to VLDL-TG.
At these visits they will consume either a ketone monoester (KME) or taste/volume-matched placebo (PLA) drink. The nature of this drink will be single blinded and consumed after the breakfast meal during the 'fed' visits.
Therefore the four visits will be as follows: fed-KME, fed-PLA, fasted-KME, fasted-PLA.
Blood and breath samples will be collected at fasting and across a 6 hour period after consuming the KME or PLA drink. Subjective measures of gastrointestinal distress and appetite will also be assessed.
This study aims to establish how feeding state might affect the appearance of βHB into the bloodstream, circulating metabolism, and hepatic metabolism.
- Conditions
- Ketosis, Exogenous Ketosis
- Being tested
- Ketone Monoester, Placebo
- Keywords
- Exogenous Ketosis, Hepatic, Metabolism, Postprandial, Postabsorptive
- Medical subject headings
- Ketosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketone MonoesterDietary supplement
Also called deltaG, (R)-3-hydroxybutyl (R)-3-hydroxybutyrate
Commercial dietary supplement intended raise blood ketone body levels
PlaceboDietary supplement
Also called Sucrose Octaacetate
Placebo drink (2mM sucrose octaacetate) taste and volume matched to the ketone monoester drinks
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Dietary Supplement: Placebo |
| Fasted - Ketone Monoester | Active comparator | Ketone monoester drink (573 mg∙kg-1 body weight) provided whilst fasted Receives: Dietary Supplement: Ketone Monoester |
| Fasted - Placebo | Placebo comparator | Placebo drink provided whilst fasted Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma β-hydroxybutyrate (βHB) kinetics
Changes in concentration of plasma βHB (mM) over the post-drink time period
Measured: 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
Measured: 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)
Measured: 7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)
Secondary outcomes (8)
Plasma biochemistry
Changes in concentration of plasma lactate, insulin, nonesterified fatty acid (NEFA), triglyceride (TG), glycerol, and urea (all mM) over the post-drink time period
Measured: 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
Changes in fatty acid composition (mol%) of VLDL-TG over the post-drink time period
Measured: 7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)
Breath acetone
Changes in concentration of breath acetone (arbitrary units) over the post-drink time period
Measured: 7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)
Urine volume
Volume (ml) of urine over the post-drink time period
Measured: 7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)
Urine composition
βHB concentration (mM) of urine over the post-drink time period
Measured: 7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)
Indirect calorimetry
Changes in Respiratory Quotient (RQ; unitless) over the post-drink time period
Measured: 7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)
Subjective measures of appetite
Changes in perceptions of appetite over the post-drink period Appetite sensations will be assessed using a validated 10-point visual analogue scale (score: 0 - minimal, 10 - maximal) which will be presented to participants on printed paper This posed four questions - "How hungry do you feel?", "How full do you feel?", "How satisfied do you feel?", and "How much do you think you can eat now?"
Measured: 7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)
Subjective measures of gastrointestinal distress
Changes in perceptions of gastrointestinal (GI) distress over the post-drink period GI distress will be assessed using a literature-standard 0-8 Likert scale questionnaire quantified at upper abdominal (reflux, bloating, nausea, vomiting), lower abdominal (cramps, flatulence, abdominal pain, diarrhoea), and systemic (dizziness, headache, muscle cramp, urge to urinate) levels (severity score: 0 - minimal, 8 - maximal)
Measured: 7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2024
- Study start15 Feb 2023
- Primary completion15 Jan 2025
- Study completion15 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for KetosisStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06320522
- Sponsor's protocol ID
- R82053/RE002
- Status last verified
- Mar 2024
- First submitted
- 5 Mar 2024
- Last updated
- 11 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterizing the Influence of Exogenous Ketosis on Circulating and Hepatic Metabolism in a Postprandial and Postabsorptive State in Adults Free From Metabolic Disease
- ClinicalTrials.gov ID
- NCT06320522
- Acronym / sponsor ID
- R82053/RE002
- Conditions
- Ketosis, Exogenous Ketosis
- Keywords
- Exogenous Ketosis, Hepatic, Metabolism, Postprandial, Postabsorptive
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- 15 Feb 2023 (actual)
- Primary completion
- 15 Jan 2025 (actual)
- Study completion
- 15 Jan 2025 (actual)
- First posted
- 20 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Adults free from metabolic disease will be recruited for this randomised-counterbalanced crossover study. Participants will attend four study visits.
Participants will consume a prescribed isocaloric high-carbohydrate diet for two days prior to each visit to standardise dietary intake.
For two of these visits participants will remain 'fasted' throughout, and for the two 'fed' visits they will consume a mixed-nutrient breakfast meal. The breakfast for the 'fed' visits will provide 2g∙kg-1 bodyweight of carbohydrate.
Heavy water (D2O) will be consumed the evening preceding, and during, each fed study visit to achieve ~0.4% plasma enrichment, in order to quantify the contribution of hepatic de novo lipogenesis to VLDL-TG.
At these visits they will consume either a ketone monoester (KME) or taste/volume-matched placebo (PLA) drink. The nature of this drink will be single blinded and consumed after the breakfast meal during the 'fed' visits.
Therefore the four visits will be as follows: fed-KME, fed-PLA, fasted-KME, fasted-PLA.
Blood and breath samples will be collected at fasting and across a 6 hour period after consuming the KME or PLA drink. Subjective measures of gastrointestinal distress and appetite will also be assessed.
This study aims to establish how feeding state might affect the appearance of βHB into the bloodstream, circulating metabolism, and hepatic metabolism.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Fed - Ketone Monoester | Active comparator | Dietary Supplement: Ketone MonoesterKetone monoester drink (573 mg∙kg-1 body weight) provided 1 hour after a 2 g∙kg-1 bodyweight of carbohydrate mixed nutrient breakfast meal |
| Fed - Placebo | Placebo comparator | Dietary Supplement: PlaceboPlacebo drink provided 1 hour after a 2 g∙kg-1 bodyweight of carbohydrate mixed nutrient breakfast meal |
| Fasted - Ketone Monoester | Active comparator | Dietary Supplement: Ketone MonoesterKetone monoester drink (573 mg∙kg-1 body weight) provided whilst fasted |
| Fasted - Placebo | Placebo comparator | Dietary Supplement: PlaceboPlacebo drink provided whilst fasted |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketone MonoesterAlso: deltaG, (R)-3-hydroxybutyl (R)-3-hydroxybutyrateCommercial dietary supplement intended raise blood ketone body levels | Dietary supplement | Fasted - Ketone Monoester, Fed - Ketone Monoester |
| PlaceboAlso: Sucrose OctaacetatePlacebo drink (2mM sucrose octaacetate) taste and volume matched to the ketone monoester drinks | Dietary supplement | Fasted - Placebo, Fed - Placebo |
Primary outcome
Plasma β-hydroxybutyrate (βHB) kinetics
Time frame: 7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)
Changes in concentration of plasma βHB (mM) over the post-drink time period
Plasma glucose kinetics
Time frame: 7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)
Changes in concentration of plasma glucose (mM) over the post-drink time period
Postprandial de novo lipogenesis (DNL)
Time frame: 7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)
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)
8 secondary outcomes
Plasma biochemistry
Time frame: 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
Time frame: 7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)
Breath acetone
Time frame: 7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)
Urine volume
Time frame: 7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)
Urine composition
Time frame: 7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)
Indirect calorimetry
Time frame: 7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)
Subjective measures of appetite
Time frame: 7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)
Subjective measures of gastrointestinal distress
Time frame: 7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ketone Monoester in people with Ketosis and Exogenous Ketosis, run by University of Oxford at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma β-hydroxybutyrate (βHB) kinetics (time frame: 7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2026.