KetosisPreKetoneNCT05581043
Pre-meals of 3-hydroxybutyrate in Type 2 Diabetes
A study testing 3-hydroxybutyrate (3-OHB) in people with Ketosis and Postprandial Hyperglycemia, run by University of Aarhus at 1 site in Denmark.
Trial summary
Hyperglycemia following meals in patients with type 2 diabetes mellitus (T2DM) is a common problem. Recently, our group found that oral consumption of the ketone metabolite, 3-hydroxybutyrate (3-OHB), effectively stimulates insulin secretion and delays gastric emptying.The aim of this study is to investigate the… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ketosis, Postprandial Hyperglycemia, Glucose Metabolism Disorders (Including Diabetes Mellitus)
- What is being tested?
- 3-hydroxybutyrate (3-OHB)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteDenmark
- Study dates
- 12 Jan 2023to 1 Jan 2024
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Older than 18 years of age
- Type 2 diabetes diagnosis
- No antiglycemic treatment or monotherapy with metformin
Who cannot join
- Hba1c > 70
- Severe liver disease (Child-Pugh score >10) or kidney disease (eGFR< 40 ml/min)
- Anemia (Hgb < 6.5 mM)
- History with pancreatitis
- Practicing ketogenic diets (i.e., low-carb diet, fasting regime)
- Inability to understand Danish or English
- Ongoing cancer or other acute/chronic serious diseases (PI will determine)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pre-meals of 3-hydroxybutyrate for People With Type 2 Diabetes
Hyperglycemia following meals in patients with type 2 diabetes mellitus (T2DM) is a common problem. Recently, our group found that oral consumption of the ketone metabolite, 3-hydroxybutyrate (3-OHB), effectively stimulates insulin secretion and delays gastric emptying.The aim of this study is to investigate the dose/response relationship between 3-OHB servings of 0, 10, 20 and 40 grams 30 minutes before an OGTT and, ii) investigate the role of timing by serving 20 grams of 3-OHB at different timepoints ahead of an OGTT (0, 30 and 60 minutes)
Read the detailed description
Hyperglycemia following meals in patients with type 2 diabetes mellitus (T2DM) is a common problem, which can cause discomfort and fatigue but may also lead to diabetic complications. Small servings of macronutrients, especially protein-rich products, before a main meal (= pre-meals) has been shown to significantly lower postprandial glucose excursions in both healthy individuals and patients with T2DM. The reductions are primarily attributed the fact that protein stimulates insulin secretion and delays gastric emptying. The timing and dose of a premeal are essential for the glycemic reductions following a meal 4. Unfortunately, it often requires a rather large amount of protein (> 50 g) to facilitate clinically relevant reductions in postprandial glucose levels and a large protein intake may be unwanted for some patients (i.e., chronic kidney disease). Recently, our group found that oral consumption of the ketone metabolite, 3- hydroxybutyrate (3-OHB), effectively stimulates insulin secretion and delays gastricemptying. We have also shown that 3-OHB inhibits gluconeogenesis 6, which may further contribute to glucose-lowering effects. Two other clinical studies have shown that serving 3- OHB before an oral glucose tolerance test (OGTT) lowered glucose excursions in healthy volunteers and persons with impaired glucose tolerance. There are no current data available about the effect of 3-OHB premeals in T2DM patients, but we have preliminary data from an ongoing trial showing that 30 g of 3-OHB served 40 min before a mixed meal test effectively lowers postprandial glucose levels (around 3 mM) in patients with T2DM. The optimal dose and timing of 3-OHB pre-meals is unknown but important before initiating long-term clinical trials. We hypothesize that pre-melas of 3-OHB will affect postprandialglucose excursions in a time-dependent matter and servings 30 minutes before an OGTT is Deleted: 4 optimal in order to lower postprandial glucose excursions. The aim of this study is therefore to i) investigate the dose/response relationship between 3-OHB servings of 0, 10, 20 and 40 grams 30 minutes before an OGTT and, ii) investigate the role of timing by serving 20 grams of 3-OHB at different timepoints ahead of an OGTT (0, 30 and 60 minutes). The primary endpoint is glucose trajectories following the OGTT. This study will give important insight into the optimal dose and timing for potential future clinical long-term studies in patients with metabolic diseases (i.e., T2DM, obesity)
- Conditions
- Ketosis, Postprandial Hyperglycemia, Glucose Metabolism Disorders (Including Diabetes Mellitus)
- Being tested
- 3-hydroxybutyrate (3-OHB)
- Medical subject headings
- Ketosis, Hyperglycemia, Glucose Metabolism Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
3-hydroxybutyrate (3-OHB)Dietary supplement
The aim of this study was therefore to i) investigate the dose/response relationship between 3-OHB servings of 0, 10, 20 and 40 grams 30 minutes before an OGTT and, ii) investigate the role of timing by serving 25 grams of 3-OHB at different timepoints ahead of an OGTT (0, 30 and 60 minutes).
| Study group | Role | What they receive |
|---|---|---|
| 0 gram 3-OHB 30 minutes before an OGTT | Placebo comparator | 0 gram 3-OHB 30 minutes before an OGTT Receives: Dietary Supplement: 3-hydroxybutyrate (3-OHB) |
| 10 gram 3-OHB 30 minutes before an OGTT | Experimental | 10 gram 3-OHB 30 minutes before an OGTT Receives: Dietary Supplement: 3-hydroxybutyrate (3-OHB) |
| 20 gram 3-OHB 30 minutes before an OGTT | Experimental | 20 gram 3-OHB 30 minutes before an OGTT Receives: Dietary Supplement: 3-hydroxybutyrate (3-OHB) |
| 40 gram 3-OHB 30 minutes before an OGTT | Experimental | 40 gram 3-OHB 30 minutes before an OGTT Receives: Dietary Supplement: 3-hydroxybutyrate (3-OHB) |
| 20 gram 3-OHB 0 minutes before an OGTT | Experimental | 20 gram 3-OHB 0 minutes before an OGTT Receives: Dietary Supplement: 3-hydroxybutyrate (3-OHB) |
| 20 gram 3-OHB 60 minutes before an OGTT | Experimental | 20 gram 3-OHB 60 minutes before an OGTT Receives: Dietary Supplement: 3-hydroxybutyrate (3-OHB) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood glucose following the OGTT
Change in blood glucose following the OGTT and compared between the different visits. Incremental change (delta) from baseline to peak. Measured with laboratory kits.
Measured: Blood samples will be obtained -60, -30, -15, 0, 15, 30, 45, 60, 90, 120, 150, 180 minutes from the OGTT
Secondary outcomes (1)
Plasma concentrations of 3-OHB, insulin, C-peptide, glucagon like peptide-1 (GLP-1), cholecystokinin (CCK), acetaminophen, free fatty acids along others.
Incremental change (delta) from baseline to peak in plasma concentrations of 3-OHB, insulin, C-peptide, glucagon like peptide-1 (GLP-1) following the OGGT and compared between the different visits. Measured with laboratory kits.
Measured: Blood samples will be obtained -60, -30, -15, 0, 15, 30, 45, 60, 90, 120, 150, 180 minutes from the OGTT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2022
- Study start12 Jan 2023
- Primary completion1 Jan 2024
- Study completion1 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for KetosisStudies of the same condition, open and under way.
- More trials run by University of AarhusThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- We will use a randomized cross-over design to investigate 10 volunteers with T2DM on six different occasions separated with at least one week.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Collaborators
- Aarhus University Hospital, Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Denmark
- Responsible party
- Sponsor
- Investigators
- Niels Møller, Professor, Study director, Professor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05581043
- Sponsor's protocol ID
- V4_03052022
- Acronym
- PreKetone
- Status last verified
- Oct 2022
- First submitted
- 4 Oct 2022
- Last updated
- 17 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Pedersen MGB, Ghias E, Bangshaab M, Loung TV, Bengtsen MB, Svart MV, Sondergaard E, Gormsen LC, Moller N, Johannsen M, Rittig N. Ketosis elevates plasma concentrations of D-beta-hydroxybutyryl-phenylalanine (BHB-Phe) in humans. Nutr Metab (Lond). 2026 Jul 15. doi: 10.1186/s12986-026-01172-7. Online ahead of print.
PubMed 42458538Bangshaab M, Bengtsen MB, Smedegaard S, Sondergaard E, Moller N, Svart MV, Rittig N. Ketone supplementation dose-dependently lowers postprandial blood glucose, lipid and ghrelin levels in individuals with type 2 diabetes: a randomised crossover study. Diabetologia. 2026 Mar;69(3):752-763. doi: 10.1007/s00125-025-06614-0. Epub 2025 Nov 28.
PubMed 41315088
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pre-meals of 3-hydroxybutyrate for People With Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT05581043
- Acronym / sponsor ID
- PreKetone / V4_03052022
- Conditions
- Ketosis, Postprandial Hyperglycemia, Glucose Metabolism Disorders (Including Diabetes Mellitus)
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Collaborators
- Aarhus University Hospital, Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Denmark
- Study start
- 12 Jan 2023 (actual)
- Primary completion
- 1 Jan 2024 (actual)
- Study completion
- 1 Jan 2024 (actual)
- First posted
- 14 Oct 2022 (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.
Hyperglycemia following meals in patients with type 2 diabetes mellitus (T2DM) is a common problem. Recently, our group found that oral consumption of the ketone metabolite, 3-hydroxybutyrate (3-OHB), effectively stimulates insulin secretion and delays gastric emptying.The aim of this study is to investigate the dose/response relationship between 3-OHB servings of 0, 10, 20 and 40 grams 30 minutes before an OGTT and, ii) investigate the role of timing by serving 20 grams of 3-OHB at different timepoints ahead of an OGTT (0, 30 and 60 minutes)
Detailed description
Hyperglycemia following meals in patients with type 2 diabetes mellitus (T2DM) is a common problem, which can cause discomfort and fatigue but may also lead to diabetic complications. Small servings of macronutrients, especially protein-rich products, before a main meal (= pre-meals) has been shown to significantly lower postprandial glucose excursions in both healthy individuals and patients with T2DM. The reductions are primarily attributed the fact that protein stimulates insulin secretion and delays gastric emptying. The timing and dose of a premeal are essential for the glycemic reductions following a meal 4. Unfortunately, it often requires a rather large amount of protein (> 50 g) to facilitate clinically relevant reductions in postprandial glucose levels and a large protein intake may be unwanted for some patients (i.e., chronic kidney disease). Recently, our group found that oral consumption of the ketone metabolite, 3- hydroxybutyrate (3-OHB), effectively stimulates insulin secretion and delays gastricemptying. We have also shown that 3-OHB inhibits gluconeogenesis 6, which may further contribute to glucose-lowering effects. Two other clinical studies have shown that serving 3- OHB before an oral glucose tolerance test (OGTT) lowered glucose excursions in healthy volunteers and persons with impaired glucose tolerance. There are no current data available about the effect of 3-OHB premeals in T2DM patients, but we have preliminary data from an ongoing trial showing that 30 g of 3-OHB served 40 min before a mixed meal test effectively lowers postprandial glucose levels (around 3 mM) in patients with T2DM. The optimal dose and timing of 3-OHB pre-meals is unknown but important before initiating long-term clinical trials. We hypothesize that pre-melas of 3-OHB will affect postprandialglucose excursions in a time-dependent matter and servings 30 minutes before an OGTT is Deleted: 4 optimal in order to lower postprandial glucose excursions. The aim of this study is therefore to i) investigate the dose/response relationship between 3-OHB servings of 0, 10, 20 and 40 grams 30 minutes before an OGTT and, ii) investigate the role of timing by serving 20 grams of 3-OHB at different timepoints ahead of an OGTT (0, 30 and 60 minutes). The primary endpoint is glucose trajectories following the OGTT. This study will give important insight into the optimal dose and timing for potential future clinical long-term studies in patients with metabolic diseases (i.e., T2DM, obesity)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 6
- Model description
- We will use a randomized cross-over design to investigate 10 volunteers with T2DM on six different occasions separated with at least one week.
| Arm | Type | Receives |
|---|---|---|
| 0 gram 3-OHB 30 minutes before an OGTT | Placebo comparator | Dietary Supplement: 3-hydroxybutyrate (3-OHB)0 gram 3-OHB 30 minutes before an OGTT |
| 10 gram 3-OHB 30 minutes before an OGTT | Experimental | Dietary Supplement: 3-hydroxybutyrate (3-OHB)10 gram 3-OHB 30 minutes before an OGTT |
| 20 gram 3-OHB 30 minutes before an OGTT | Experimental | Dietary Supplement: 3-hydroxybutyrate (3-OHB)20 gram 3-OHB 30 minutes before an OGTT |
| 40 gram 3-OHB 30 minutes before an OGTT | Experimental | Dietary Supplement: 3-hydroxybutyrate (3-OHB)40 gram 3-OHB 30 minutes before an OGTT |
| 20 gram 3-OHB 0 minutes before an OGTT | Experimental | Dietary Supplement: 3-hydroxybutyrate (3-OHB)20 gram 3-OHB 0 minutes before an OGTT |
| 20 gram 3-OHB 60 minutes before an OGTT | Experimental | Dietary Supplement: 3-hydroxybutyrate (3-OHB)20 gram 3-OHB 60 minutes before an OGTT |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Older than 18 years of age
- Type 2 diabetes diagnosis
- No antiglycemic treatment or monotherapy with metformin
Key exclusion criteria (7 listed)
- Hba1c > 70
- Severe liver disease (Child-Pugh score >10) or kidney disease (eGFR< 40 ml/min)
- Anemia (Hgb < 6.5 mM)
- History with pancreatitis
- Practicing ketogenic diets (i.e., low-carb diet, fasting regime)
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 |
|---|---|---|
| 3-hydroxybutyrate (3-OHB)The aim of this study was therefore to i) investigate the dose/response relationship between 3-OHB servings of 0, 10, 20 and 40 grams 30 minutes before an OGTT and, ii) investigate the role of timing by serving 25 grams of 3-OHB at different timepoints ahead of an OGTT (0, 30 and 60 minutes). | Dietary supplement | 0 gram 3-OHB 30 minutes before an OGTT, 10 gram 3-OHB 30 minutes before an OGTT, 20 gram 3-OHB 0 minutes before an OGTT, 20 gram 3-OHB 30 minutes before an OGTT, 20 gram 3-OHB 60 minutes before an OGTT, 40 gram 3-OHB 30 minutes before an OGTT |
Primary outcome
Blood glucose following the OGTT
Time frame: Blood samples will be obtained -60, -30, -15, 0, 15, 30, 45, 60, 90, 120, 150, 180 minutes from the OGTT
Change in blood glucose following the OGTT and compared between the different visits. Incremental change (delta) from baseline to peak. Measured with laboratory kits.
1 secondary outcome
Plasma concentrations of 3-OHB, insulin, C-peptide, glucagon like peptide-1 (GLP-1), cholecystokinin (CCK), acetaminophen, free fatty acids along others.
Time frame: Blood samples will be obtained -60, -30, -15, 0, 15, 30, 45, 60, 90, 120, 150, 180 minutes from the OGTT
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 17 Jan 2024.
- Derived from this study: PubMed 42458538Pedersen MGB, Ghias E, Bangshaab M, Loung TV, Bengtsen MB, Svart MV, Sondergaard E, Gormsen LC, Moller N, Johannsen M, Rittig N. Ketosis elevates plasma concentrations of D-beta-hydroxybutyryl-phenylalanine (BHB-Phe) in humans. Nutr Metab (Lond). 2026 Jul 15. doi: 10.1186/s12986-026-01172-7. Online ahead of print.
- Derived from this study: PubMed 41315088Bangshaab M, Bengtsen MB, Smedegaard S, Sondergaard E, Moller N, Svart MV, Rittig N. Ketone supplementation dose-dependently lowers postprandial blood glucose, lipid and ghrelin levels in individuals with type 2 diabetes: a randomised crossover study. Diabetologia. 2026 Mar;69(3):752-763. doi: 10.1007/s00125-025-06614-0. Epub 2025 Nov 28.
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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.
Niels Møller, Professor study director
Professor
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 3-hydroxybutyrate (3-OHB) in people with Ketosis and Postprandial Hyperglycemia, run by University of Aarhus at 1 site in Denmark.
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 3 inclusion and 7 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 17 Jan 2024. 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 Denmark. 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?
Blood glucose following the OGTT (time frame: Blood samples will be obtained -60, -30, -15, 0, 15, 30, 45, 60, 90, 120, 150, 180 minutes from the OGTT). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05581043, which also lists 2 linked publications.
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 17 Jan 2024.