Exogenous Ketone Ester in Women With Polycystic Ovary Syndrome.

Sponsor

University of Aarhus (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05762822

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief 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 3-OHB supplement acutely improves the hormonal and metabolic status in women with PCOS.

Condition or Disease	Intervention/Treatment	Phase
PCOS	Dietary Supplement: 3-OHB (KE4) Dietary Supplement: water	N/A

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

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Power calculation resulted in n=18 for the primary endpoint. We plan to include n=30 to ensure statistical power and take dropouts, missing values etc into account.Power calculation resulted in n=18 for the primary endpoint. We plan to include n=30 to ensure statistical power and take dropouts, missing values etc into account.

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Exogenous Ketone Ester in Women With Polycystic Ovary Syndrome.

Anticipated Study Start Date :

Apr 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo 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).	Dietary Supplement: water 60 ml water (added bitter taste)
Active Comparator: 3-OHB 60 ml 3-OHB (30 g) at 10 pm the night before and 6 am on the day for blood sampling (8 am).	Dietary Supplement: 3-OHB (KE4) 60 ml (30 g) of 3-OHB Other Names: ketone supplement

Arm

Intervention/Treatment

Placebo Comparator: Placebo

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).

Dietary Supplement: water

60 ml water (added bitter taste)

Active Comparator: 3-OHB

60 ml 3-OHB (30 g) at 10 pm the night before and 6 am on the day for blood sampling (8 am).

Dietary Supplement: 3-OHB (KE4)

60 ml (30 g) of 3-OHB

Other Names:

ketone supplement

Outcome Measures

Primary Outcome Measures

Plasma concentration of testosterone [10 hours after first intervention]
Paired t-test

Secondary Outcome Measures

plasma SHBG [10 hours after first intervention]
plasma 3-OHB [10 hours after first intervention]
plasma glucose [10 hours after first intervention]
serum insulin [10 hours after first intervention]
plasma C-peptide [10 hours after first intervention]
plasma free fatty acids [10 hours after first intervention]
plasma triglycerides [10 hours after first intervention]
plasma cholesterol [10 hours after first intervention]
C reactive protein [10 hours after first intervention]
plasma cytokines (such as Tumor Necrotic Factor alpha, Interleukin 6, Lipopolysaccharide -binding protein, soluble CD163) [10 hours after first intervention]
plasma prolactin [10 hours after first intervention]
Plasma FSH [10 hours after first intervention]
Plasma LH [10 hours after first intervention]
plasma free testosterone [10 hours after first intervention]
plasma estradiol [10 hours after first intervention]
plasma keto-testosterone [10 hours after first intervention]
Homeostatic Model Assessment for Insulin Resistance [10 hours after first intervention]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

PCOS diagnosis
age >18 years

Exclusion Criteria:

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)