Clinical trial NCT05762822: Exogenous Ketone Ester in Women with Polycystic Ovary Syndrome.
Official title: Exogenous Ketone Ester in Women with Polycystic Ovary Syndrome.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: PCOS
Keywords: 3-hydroxybutyrate
ketones
metabolism
testosterone
androgens
KetoneAid
Ketone monoester
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2023-03-10
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Plasma concentration of testosterone
timeFrame: 10 hours after first intervention
Secondary outcomes:
measure: plasma SHBG
timeFrame: 10 hours after first intervention
measure: plasma 3-OHB
timeFrame: 10 hours after first intervention
measure: plasma glucose
timeFrame: 10 hours after first intervention
measure: serum insulin
timeFrame: 10 hours after first intervention
measure: plasma C-peptide
timeFrame: 10 hours after first intervention
measure: plasma free fatty acids
timeFrame: 10 hours after first intervention
measure: plasma triglycerides
timeFrame: 10 hours after first intervention
measure: plasma cholesterol
timeFrame: 10 hours after first intervention
measure: C reactive protein
timeFrame: 10 hours after first intervention
measure: plasma cytokines (such as Tumor Necrotic Factor alpha, Interleukin 6, Lipopolysaccharide -binding protein, soluble CD163)
timeFrame: 10 hours after first intervention
measure: plasma prolactin
timeFrame: 10 hours after first intervention
measure: Plasma FSH
timeFrame: 10 hours after first intervention
measure: Plasma LH
timeFrame: 10 hours after first intervention
measure: plasma free testosterone
timeFrame: 10 hours after first intervention
measure: plasma estradiol
timeFrame: 10 hours after first intervention
measure: plasma keto-testosterone
timeFrame: 10 hours after first intervention
measure: Homeostatic Model Assessment for Insulin Resistance
timeFrame: 10 hours after first intervention
Other outcomes:
Locations:
city: Aarhus N
country: Denmark
facility: Department of Diabetes and Hormone Diseases (DoH)
Study officials:
affiliation: University of Aarhus
name: Nikolaj Rittig
role: PRINCIPAL_INVESTIGATOR
References: