Exogenous Ketone Supplementation in Females with Polycystic Ovary Syndrome

NCT06155708 | Recruiting

• 1 other identifier: 2024-9710
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (4)

• Glycemic responses to a 2-hr oral glucose tolerance test

  \- Glucose is calculated by the area under the curve using the trapezoid method.

  0-2.5 hours in the post-prandial period

• Flow mediated dilation (FMD)

  \- Endothelial function is assessed using the standard FMD; quantified as the percent increase in diameter from rest to peak diameter observed during reactive hyperemia (%FMD). The % change in diameter reflects the ability of the vessel to dilate in response to sheer stress induced by the flow following the release of occlusion. This reflects the function of the endothelium, or release of nitric oxide.

  30 minutes

• Systolic Blood Pressure (SBP)

  \- SBP, measured in mmHg

  2 hours

• Diastolic Blood Pressure (DBP)

  \- DBP, measured in mmHg

  2 hours

Secondary Outcomes (16)

• Insulin area under the curve

  0-2.5 hours in the post-prandial period

• C-peptide

  0-2.5 hours in the post-prandial period

• Glucagon-like peptide-1 (GLP-1)

  0-2.5 hours in the post-prandial period

• Glucose-dependent insulinotropic polypeptide (GIP)

  0-2.5 hours in the post-prandial period

• Triglycerides

  0-2.5 hours in the post-prandial period

Study Arms (2)

Ketone

EXPERIMENTAL

\- Ketone monoester supplement in the form of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate based on participants' body weight (0.45ml/kg body weight) ingested with water and vanilla-flavored stevia in a total volume of 100 ml.

Dietary Supplement: Ketone

Placebo

PLACEBO COMPARATOR

100 ml water combined with 10ml bitter flavor and vanilla-flavored stevia

Dietary Supplement: Water

Interventions

Ketone DIETARY_SUPPLEMENT

\- Ketone monoester supplement in the form of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate based on participants' body weight (0.45ml/kg body weight) ingested with water and vanilla-flavored stevia in a total volume of 100 ml.

Ketone

Water DIETARY_SUPPLEMENT

100 ml water combined with 10ml bitter flavor and vanilla-flavored stevia

Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• McGill University: lead

Study Sites (1)

Cardiovascular Health and Autonomic Research Laboratory

Montreal, Quebec, H2W 1S4, Canada

RECRUITING

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Insulin Resistance

Interventions

Ketones; Water

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Organic Chemicals; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds

Study Officials

• Charlotte Usselman, Ph.D

  McGill University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Charlotte Usselman, Ph.D

CONTACT

5143962140; charlotte.usselman@mcgill.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Primary Investigator

Study Record Dates

• First Submitted: October 18, 2023
• First Posted: December 4, 2023
• Study Start: January 20, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: January 22, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)