PCOSNCT05762822
Exogenous Ketone Ester in Women with Polycystic Ovary Syndrome.
A study testing 3-OHB (KE4) and water in people with PCOS, run by University of Aarhus at 1 site in Denmark.
Trial summary
Polycystic ovarian syndrome (PCOS) is characterized by elevated androgens such as testosterone. Clinical studies suggest that ketogenic diets lower the levels of androgens. The ketone 3-hydroxybutyrate (3-OHB) may play an important role in these effects and the main purpose of this study is to investigate whether a… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- PCOS
- What is being tested?
- 3-OHB (KE4) and water
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteDenmark
- Study dates
- 10 May 2023to 30 Oct 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- PCOS diagnosis
- age >18 years
Who cannot join
- Medications affecting sex hormones (e.g. contraceptives, dopamine agonists, etc) or glucose metabolism (e.g. saxenda).
- Anemia (Hgb < 6.0 mM)
- Practicing ketogenic diets (e.g., low-carb diet, fasting regimes)
- Inability to understand Danish or English
- Diabetes
- Ongoing cancer or other acute/chronic serious diseases (PI will determine)
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Department of Diabetes and Hormone Diseases (DoH)
Aarhus N, 8200
About this study
Polycystic ovarian syndrome (PCOS) is characterized by elevated androgens such as testosterone. Clinical studies suggest that ketogenic diets lower the levels of androgens. The ketone 3-hydroxybutyrate (3-OHB) may play an important role in these effects and the main purpose of this study is to investigate whether a 3-OHB supplement acutely improves the hormonal and metabolic status in women with PCOS.
Read the detailed description
Polycystic ovary syndrome (PCOS) affects 5-18% of women and is characterized by the presence of two of three of the Rotterdam criteria: Hyperandrogenism (clinical or biochemical), irregular menstrual cycles, and polycystic ovary morphology, after exclusion of other conditions that mimic PCOS. PCOS is associated with elevated levels of luteinizing hormone (LH) and unaltered levels of the follicle stimulating hormone (FSH), which leads to the characteristic hyperandrogenism (high levels of testosterone), oligo- or anovulation, and a large number of premature follicles in the ovarian. Insulin resistance causes hyperinsulinemia that decreases sex hormone binding globulin (SHBG) levels and stimulates androgen production (e.g., elevated concentrations of testosterone). Ketogenic diets are characterized by a diet low in carbohydrates, and has shown beneficial effects on weight and hormonal status in women with PCOS. Whether these improvements are mediated by ketones (e.g., 3-hydroxybutyrate, 3-OHB) or other effects related to this diet is unknown. The main purpose of this study is to investigate whether a 3-OHB supplement acutely improves the hormonal and metabolic status in women with PCOS.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
3-OHB (KE4)Dietary supplement
Also called ketone supplement
60 ml (30 g) of 3-OHB
waterDietary supplement
60 ml water (added bitter taste)
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | 60 ml water (same taste as active comparator) at 10 pm the night before and 6 am on the day for blood sampling (8 am). Receives: Dietary Supplement: water |
| 3-OHB | Active comparator | 60 ml 3-OHB (30 g) at 10 pm the night before and 6 am on the day for blood sampling (8 am). Receives: Dietary Supplement: 3-OHB (KE4) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma concentration of testosterone
Paired t-test
Measured: 10 hours after first intervention
Secondary outcomes (17)
plasma SHBG
Measured: 10 hours after first intervention
plasma 3-OHB
Measured: 10 hours after first intervention
plasma glucose
Measured: 10 hours after first intervention
serum insulin
Measured: 10 hours after first intervention
plasma C-peptide
Measured: 10 hours after first intervention
plasma free fatty acids
Measured: 10 hours after first intervention
plasma triglycerides
Measured: 10 hours after first intervention
plasma cholesterol
Measured: 10 hours after first intervention
C reactive protein
Measured: 10 hours after first intervention
plasma cytokines (such as Tumor Necrotic Factor alpha, Interleukin 6, Lipopolysaccharide -binding protein, soluble CD163)
Measured: 10 hours after first intervention
plasma prolactin
Measured: 10 hours after first intervention
Plasma FSH
Measured: 10 hours after first intervention
Plasma LH
Measured: 10 hours after first intervention
plasma free testosterone
Measured: 10 hours after first intervention
plasma estradiol
Measured: 10 hours after first intervention
plasma keto-testosterone
Measured: 10 hours after first intervention
Homeostatic Model Assessment for Insulin Resistance
Measured: 10 hours after first intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2023
- Study start10 May 2023
- Primary completion30 Oct 2024
- Study completion30 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PCOSStudies 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
- Power calculation resulted in n=18 for the primary endpoint. We plan to include n= 20 to ensure statistical power and take dropouts, missing values etc into account. Washout period of minimum 3 days.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nikolaj Rittig, Principal investigator, University of Aarhus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05762822
- Sponsor's protocol ID
- 1-10-72-217-22
- Status last verified
- Oct 2024
- First submitted
- 15 Feb 2023
- Last updated
- 4 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Rittig N, Christiansen Arlien-Soborg M, Svart MV, Thomsen HH, Kirkegaard K, Greve VH, Nielsen MM, Stochholm K, Ornstrup MJ, Gravholt CH. Ketone supplementation acutely lowers androgen and glucose levels in women with polycystic ovary syndrome: a randomized clinical trial. Eur J Endocrinol. 2025 May 30;192(6):717-727. doi: 10.1093/ejendo/lvaf106.
PubMed 40393075
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exogenous Ketone Ester in Women with Polycystic Ovary Syndrome.
- ClinicalTrials.gov ID
- NCT05762822
- Acronym / sponsor ID
- 1-10-72-217-22
- Conditions
- PCOS
- Keywords
- 3-hydroxybutyrate, ketones, metabolism, testosterone, androgens, KetoneAid, Ketone monoester
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Study start
- 10 May 2023 (actual)
- Primary completion
- 30 Oct 2024 (actual)
- Study completion
- 30 Oct 2024 (actual)
- First posted
- 10 Mar 2023 (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.
Polycystic ovarian syndrome (PCOS) is characterized by elevated androgens such as testosterone. Clinical studies suggest that ketogenic diets lower the levels of androgens. The ketone 3-hydroxybutyrate (3-OHB) may play an important role in these effects and the main purpose of this study is to investigate whether a 3-OHB supplement acutely improves the hormonal and metabolic status in women with PCOS.
Detailed description
Polycystic ovary syndrome (PCOS) affects 5-18% of women and is characterized by the presence of two of three of the Rotterdam criteria: Hyperandrogenism (clinical or biochemical), irregular menstrual cycles, and polycystic ovary morphology, after exclusion of other conditions that mimic PCOS. PCOS is associated with elevated levels of luteinizing hormone (LH) and unaltered levels of the follicle stimulating hormone (FSH), which leads to the characteristic hyperandrogenism (high levels of testosterone), oligo- or anovulation, and a large number of premature follicles in the ovarian. Insulin resistance causes hyperinsulinemia that decreases sex hormone binding globulin (SHBG) levels and stimulates androgen production (e.g., elevated concentrations of testosterone). Ketogenic diets are characterized by a diet low in carbohydrates, and has shown beneficial effects on weight and hormonal status in women with PCOS. Whether these improvements are mediated by ketones (e.g., 3-hydroxybutyrate, 3-OHB) or other effects related to this diet is unknown. The main purpose of this study is to investigate whether a 3-OHB supplement acutely improves the hormonal and metabolic status in women with PCOS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Power calculation resulted in n=18 for the primary endpoint. We plan to include n= 20 to ensure statistical power and take dropouts, missing values etc into account. Washout period of minimum 3 days.
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Dietary Supplement: water60 ml water (same taste as active comparator) at 10 pm the night before and 6 am on the day for blood sampling (8 am). |
| 3-OHB | Active comparator | Dietary Supplement: 3-OHB (KE4)60 ml 3-OHB (30 g) at 10 pm the night before and 6 am on the day for blood sampling (8 am). |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- PCOS diagnosis
- age >18 years
Key exclusion criteria (6 listed)
- Medications affecting sex hormones (e.g. contraceptives, dopamine agonists, etc) or glucose metabolism (e.g. saxenda).
- Anemia (Hgb < 6.0 mM)
- Practicing ketogenic diets (e.g., low-carb diet, fasting regimes)
- Inability to understand Danish or English
- Diabetes
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-OHB (KE4)Also: ketone supplement60 ml (30 g) of 3-OHB | Dietary supplement | 3-OHB |
| water60 ml water (added bitter taste) | Dietary supplement | Placebo |
Primary outcome
Plasma concentration of testosterone
Time frame: 10 hours after first intervention
Paired t-test
17 secondary outcomes
plasma SHBG
Time frame: 10 hours after first intervention
plasma 3-OHB
Time frame: 10 hours after first intervention
plasma glucose
Time frame: 10 hours after first intervention
serum insulin
Time frame: 10 hours after first intervention
plasma C-peptide
Time frame: 10 hours after first intervention
plasma free fatty acids
Time frame: 10 hours after first intervention
plasma triglycerides
Time frame: 10 hours after first intervention
plasma cholesterol
Time frame: 10 hours after first intervention
C reactive protein
Time frame: 10 hours after first intervention
plasma cytokines (such as Tumor Necrotic Factor alpha, Interleukin 6, Lipopolysaccharide -binding protein, soluble CD163)
Time frame: 10 hours after first intervention
plasma prolactin
Time frame: 10 hours after first intervention
Plasma FSH
Time frame: 10 hours after first intervention
Plasma LH
Time frame: 10 hours after first intervention
plasma free testosterone
Time frame: 10 hours after first intervention
plasma estradiol
Time frame: 10 hours after first intervention
plasma keto-testosterone
Time frame: 10 hours after first intervention
Homeostatic Model Assessment for Insulin Resistance
Time frame: 10 hours after first intervention
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 4 Nov 2024.
- Derived from this study: PubMed 40393075Rittig N, Christiansen Arlien-Soborg M, Svart MV, Thomsen HH, Kirkegaard K, Greve VH, Nielsen MM, Stochholm K, Ornstrup MJ, Gravholt CH. Ketone supplementation acutely lowers androgen and glucose levels in women with polycystic ovary syndrome: a randomized clinical trial. Eur J Endocrinol. 2025 May 30;192(6):717-727. doi: 10.1093/ejendo/lvaf106.
- Individual participant dataSharing planned: Undecided
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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.
Nikolaj Rittig principal investigator
University of Aarhus
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-OHB (KE4) and water in people with PCOS, 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 2 inclusion and 6 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 4 Nov 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?
Plasma concentration of testosterone (time frame: 10 hours after first intervention). 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 NCT05762822, which also lists 1 linked publication.
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 4 Nov 2024.