Symptoms of Polycystic Ovarian Syndrome Ameliorated by Keto-Adaptation Pilot

NCT ID: NCT07227363

Last Updated: 2025-11-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-01
• Study Completion Date: 2026-12-31

Brief Summary

The SPARK- Pilot study (Symptoms of PCOS Ameliorated by Responses to Keto-adaptation) is a 12-week clinical trial at The Ohio State University designed to explore how different ways of achieving ketosis may improve reproductive and metabolic health in women with Polycystic Ovary Syndrome (PCOS).

Participants will be randomly assigned to one of two groups:

• A ketogenic diet group, following a low-carbohydrate, nutrient-dense meal plan.
• A mixed diet plus ketone supplement group, following general dietary guidelines while taking an exogenous ketone supplement.

The study will measure whether these approaches help restore regular ovulation and improve hormone balance, metabolism, and overall well-being. Optional imaging using MRI will also examine heart and ovarian health.

This pilot study will help researchers understand if ketogenic nutrition strategies are a safe, effective way to support menstrual regularity and reduce PCOS-related symptoms, providing groundwork for larger clinical trials.

Detailed Description

The SPARK study (Symptoms of PCOS Ameliorated by Responses to Keto-adaptation) is a 12-week randomized, two-arm intervention examining how nutritional ketosis influences ovulatory and metabolic outcomes in women with Polycystic Ovary Syndrome (PCOS).

PCOS is a common endocrine disorder that affects hormone balance, menstrual function, and metabolism. Current treatments often address single symptoms but rarely provide comprehensive improvement. Ketogenic dietary interventions have shown promise for improving insulin sensitivity, hormone profiles, and body composition; however, few studies have evaluated their direct impact on ovulation.

In this pilot trial, 40 women aged 18-40 years with diagnosed PCOS will be randomized to one of two groups:

Ketogenic Diet (KD): Participants will follow a low-carbohydrate, high-fat, moderate-protein diet designed to achieve and maintain nutritional ketosis (β-hydroxybutyrate ≥0.5 mmol/L).

Mixed Diet + Exogenous Ketone Supplement: Participants will consume a balanced diet aligned with USDA macronutrient recommendations and receive a ketone ester supplement.

Primary outcomes include changes in ovulatory status, assessed through hormonal markers, ovulation prediction tests, and continuous basal body temperature monitoring (OvuSense). Secondary outcomes include changes in reproductive hormones (progesterone, estrogen, LH, FSH), metabolic and lipid markers, and exploratory imaging of cardiovascular function and ovarian morphology via MRI.

This study will provide feasibility and preliminary efficacy data to inform a future large-scale clinical trial evaluating ketogenic strategies for improving menstrual regularity and overall health in women with PCOS.

Conditions

PCOS (Polycystic Ovary Syndrome)

Keywords

Ketogenic Diet; Exogenous Ketones; Nutritional Ketosis; Reproductive Hormones; Ovarian Function; Women's Health; Metabolic Health; PCOS

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Ketogenic Diet (KD)

Participants in this arm will follow a well-formulated ketogenic diet designed to achieve and maintain nutritional ketosis (β-hydroxybutyrate ≥0.5 mmol/L). The diet will include non-starchy vegetables as the primary carbohydrate source (20-50 g/day), moderate protein (1.2-1.6 g/kg/day), and sufficient fat for energy and satiety. All meals and snacks will be provided for the first 2 weeks, followed by self-guided adherence with support from the study dietitian and educational resources. Daily fingerstick ketone and glucose levels will be monitored using KetoMojo.

Group Type: EXPERIMENTAL

Ketogenic diet

Intervention Type: OTHER

A well-formulated ketogenic diet designed to achieve nutritional ketosis (β-hydroxybutyrate ≥0.5 mmol/L). The diet emphasizes non-starchy vegetables as the primary carbohydrate source (20-50 g/day), moderate protein intake (1.2-1.6 g/kg/day), and sufficient dietary fat for energy and satiety. All meals and snacks will be provided during the initial two weeks, followed by a self-guided phase with ongoing dietitian support and education materials. Participants will monitor daily fasting ketones and glucose using a handheld analyzer (KetoMojo).

Mixed Diet + Exogenous Ketone Supplement

Participants in this arm will follow a balanced, mixed diet aligned with USDA macronutrient recommendations while consuming an exogenous ketone supplement throughout the 12-week intervention. The supplement is designed to raise circulating β-hydroxybutyrate to nutritional ketosis levels without carbohydrate restriction. As with the KD arm, all meals and snacks will be provided for the first 2 weeks, followed by self-guided adherence with ongoing dietitian support.

Group Type: ACTIVE_COMPARATOR

Exogenous Ketone Supplement

Intervention Type: DIETARY_SUPPLEMENT

A dietary supplement containing a ketone ester designed to elevate circulating β-hydroxybutyrate concentrations to nutritional ketosis levels without carbohydrate restriction. Participants will consume the supplement throughout the 12-week intervention while following a balanced, mixed diet consistent with USDA dietary guidelines.

Interventions

Ketogenic diet

A well-formulated ketogenic diet designed to achieve nutritional ketosis (β-hydroxybutyrate ≥0.5 mmol/L). The diet emphasizes non-starchy vegetables as the primary carbohydrate source (20-50 g/day), moderate protein intake (1.2-1.6 g/kg/day), and sufficient dietary fat for energy and satiety. All meals and snacks will be provided during the initial two weeks, followed by a self-guided phase with ongoing dietitian support and education materials. Participants will monitor daily fasting ketones and glucose using a handheld analyzer (KetoMojo).

Intervention Type: OTHER

Exogenous Ketone Supplement

A dietary supplement containing a ketone ester designed to elevate circulating β-hydroxybutyrate concentrations to nutritional ketosis levels without carbohydrate restriction. Participants will consume the supplement throughout the 12-week intervention while following a balanced, mixed diet consistent with USDA dietary guidelines.

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• Female participants aged 18-40 years.
• Clinical diagnosis of Polycystic Ovary Syndrome (PCOS) according to Rotterdam criteria (presence of at least two of the following: oligo- or anovulation, clinical or biochemical signs of hyperandrogenism, and/or polycystic ovaries on ultrasound).
• Willingness and ability to comply with all study procedures, including fasting (>10 hours; water only), avoidance of alcohol (>24 hours), and abstaining from exercise (>24 hours) prior to each test visit.
• Willing to maintain current diet, exercise, medication, and supplement habits throughout the study.
• Body mass index (BMI) ≥18 kg/m².
• Access to a smartphone, computer, or tablet for digital tracking and study communication.

Exclusion Criteria

• Current adherence to a low-carbohydrate diet (<30% of total energy from carbohydrates).
• Non-PCOS etiologies of anovulation (e.g., menopause, oophorectomy, or other reproductive disorders).
• History of type 1 diabetes or uncontrolled type 2 diabetes.
• Weight loss ≥10% of body weight within the previous 6 months.
• Pregnancy or breastfeeding.
• Use of hormonal contraception or medications known to alter reproductive hormones within 3 months prior to enrollment.
• Active eating disorder or medical condition that could interfere with dietary intervention.
• Any condition that, in the opinion of the Investigator, could interfere with participation, data integrity, or safety.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Ohio State University

OTHER

Sponsor Role: lead

Responsible Party

Madison Kackley

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Madison Kackley, PhD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

The Ohio State University

Columbus, Ohio, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Madison Kackley, PhD

Role: CONTACT

Phone: 16142479650

Email: Kackley.19@osu.edu

Facility Contacts

Madison Kackley

Role: primary

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

2023H0368

Identifier Type: -

Identifier Source: org_study_id