Symptoms of Polycystic Ovarian Syndrome Ameliorated by Keto-Adaptation Pilot

NCT07227363 | Recruiting DMC

• 1 other identifier: 2023H0368
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

PCOS (Polycystic Ovary Syndrome)

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Change in Ovulatory Status

  To evaluate whether ketogenic dietary intervention or exogenous ketone supplementation restores ovulatory function in women with Polycystic Ovary Syndrome (PCOS). Ovulatory status will be assessed using a combination of validated measures, including basal body temperature monitoring via BBT, urinary luteinizing hormone (LH) surge detection using ovulation predictor kits, and serum progesterone levels. Participants will be classified as ovulatory or anovulatory based on hormonal and temperature cycle confirmation.

  Baseline to 12 weeks

Secondary Outcomes (11)

• Change in Serum Progesterone Concentration (ng/mL)

  Baseline to 12 weeks

• Change in Serum Estradiol Concentration (pg/mL)

  Baseline to 12 weeks

• Change in Serum Luteinizing Hormone Concentration (mIU/mL)

  Baseline to 12 weeks

• Change in Serum Follicle Stimulating Hormone Concentrations (mIU/mL)

  Baseline to 12 weeks

• Change in Daily Fasting BHB (mmol/L)

  Baseline to 12 weeks (Daily)

Study Arms (2)

Ketogenic Diet (KD)

EXPERIMENTAL

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.

Other: Ketogenic diet

Mixed Diet + Exogenous Ketone Supplement

ACTIVE COMPARATOR

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.

Dietary Supplement: Exogenous Ketone Supplement

Interventions

Ketogenic diet 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).

Ketogenic Diet (KD)

Exogenous Ketone Supplement 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.

Mixed Diet + Exogenous Ketone Supplement

Eligibility Criteria

• Age: 18 Years - 40 Years
• Gender Eligibility Details: This study enrolls biological females aged 18-40 years who have been clinically diagnosed with PCOS. Because the primary outcomes involve menstrual cyclicity, ovulatory function, and reproductive hormone regulation, eligibility is limited to individuals assigned female at birth. Self-identified women meeting these criteria are eligible to participate, regardless of gender identity, provided they have intact ovarian function and are not pregnant or breastfeeding.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ohio State University: lead

Study Sites (1)

The Ohio State University

Columbus, Ohio, 43210-1442, United States

RECRUITING

MeSH Terms

Conditions

Polycystic Ovary Syndrome

Interventions

Diet, Ketogenic

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

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Madison Kackley, PhD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Madison Kackley, PhD

CONTACT

16142479650; Kackley.19@osu.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is a pilot feasibility study; therefore, no masking will be implemented. Participants and investigators will be aware of group assignments due to the distinct nature of the dietary and supplement interventions. The study is designed as an open-label trial to evaluate adherence, feasibility, and physiological responses to each intervention before planning a larger randomized, controlled study.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: November 6, 2025
• First Posted: November 12, 2025
• Study Start: February 1, 2025
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 12, 2025

Record last verified: 2025-11

Locations

US (1)