Clinical trial NCT06155708: Exogenous Ketone Supplementation in Females with Polycystic Ovary Syndrome
Official title: Exogenous Ketone Supplementation to Improve Cardiovascular Disease Risk Factors in Females with Polycystic Ovary Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: PCOS
Keywords: Polycystic ovary syndrome
Ketone monoester ingestion
Insulin resistance
Endothelial function
Blood pressure
Oral glucose tolerance test
Flow mediated dilation
Handgrip exercise
Neurovascular transduction
Cold pressor test
Lead sponsor: McGill University
Sponsor class: OTHER
First posted: 2023-12-04
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Polycystic ovary syndrome (PCOS) affects 1 in 5 females of reproductive age. Commonly characterized as a disorder of infertility, PCOS is often accompanied by 3 potent cardiovascular disease (CVD) risk factors: insulin resistance, endothelial dysfunction, and elevated blood pressure. Accordingly, PCOS is associated with the development of CVD, the second leading cause of death in females in Canada. However, effective treatments to improve cardiovascular health in PCOS are lacking.

Exogenous ketone monoester (KME) ingestion has been shown to improves outcomes associated with insulin resistance, endothelial function, and blood pressure regulation in healthy individuals and individuals predisposed to CVD. Therefore, oral ketone supplements offer a practical and effective strategy for improving cardiovascular health; however, this treatment has yet to be evaluated in PCOS.

Therefore, the overall goal of this project is to employ KME ingestion to improve markers of cardiovascular health in females with PCOS.

On two different days, participants will consume either a beverage containing a ketone supplement or a beverage containing a placebo supplement. The objectives are to compare responses between KME and placebo ingestion, and examine all outcomes related to cardiovascular health in females with PCOS in comparison with female controls of similar age and body mass index. The effects of KME ingestion will be quantified on: 1) glycemic control during an oral glucose tolerance test; 2) endothelial function using the flow-mediated dilation test; 3) blood pressure and acute blood pressure regulation; and 4) hemodynamic responses to acute exercise.


Eligibility criteria: Inclusion Criteria:

* All female participants will report female sex assigned at birth
* All participants will be aged 18 to 40
* PCOS diagnosis

Exclusion Criteria:

* Current smokers or a prolonged history of smoking
* Presence or history of overt cardiometabolic disease (e.g., stage 2 hypertension, diabetes, heart disease), neurologic disease, or endocrinopathy (with the exception of PCOS)
* Current pregnancy or currently breastfeeding
* Current use of medications which may affect our outcomes of interest (e.g., anti-hypertensives, anti-androgens, metformin)

Primary outcomes:
measure: Glycemic responses to a 2-hr oral glucose tolerance test
timeFrame: 0-2.5 hours in the post-prandial period
measure: Flow mediated dilation (FMD)
timeFrame: 30 minutes
measure: Systolic Blood Pressure (SBP)
timeFrame: 2 hours
measure: Diastolic Blood Pressure (DBP)
timeFrame: 2 hours
Secondary outcomes:
measure: Insulin area under the curve
timeFrame: 0-2.5 hours in the post-prandial period
measure: C-peptide
timeFrame: 0-2.5 hours in the post-prandial period
measure: Glucagon-like peptide-1 (GLP-1)
timeFrame: 0-2.5 hours in the post-prandial period
measure: Glucose-dependent insulinotropic polypeptide (GIP)
timeFrame: 0-2.5 hours in the post-prandial period
measure: Triglycerides
timeFrame: 0-2.5 hours in the post-prandial period
measure: Insulinogenic index
timeFrame: 0-2.5 hours in the post-prandial period
measure: Arterial artery blood flow
timeFrame: 0-2.5 hours in the post-prandial period
measure: Shear rate and low-flow mediated vasoconstriction to the FMD
timeFrame: 30 minutes
measure: Muscle sympathetic nerve activity (MSNA)
timeFrame: 2 hours
measure: Neurovascular transduction
timeFrame: 2 hours
measure: Vascular resistance
timeFrame: 2 hours
measure: Capillary blood Beta-OHB concentrations
timeFrame: 0-2.5 hours in the post-prandial period
measure: Serum testosterone
timeFrame: 5 minutes
measure: Serum sex hormone binding globulin
timeFrame: 5 minutes
measure: Serum estradiol
timeFrame: 5 minutes
measure: Serum Progesterone
timeFrame: 5 minutes
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: Cardiovascular Health and Autonomic Research Laboratory
state: Quebec
Study officials:
affiliation: McGill University
name: Charlotte Usselman, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: