Symptoms of Polycystic Ovarian Syndrome Ameliorated by Keto-Adaptation Pilot ((SPARK-Pilot))

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.

Study Overview

• Status: Recruiting
• Conditions: PCOS (Polycystic Ovary Syndrome)
• Intervention / Treatment: Other: Ketogenic diet; Dietary supplement: Exogenous Ketone Supplement

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Madison Kackley, PhD; Phone Number: 16142479650; Email: Kackley.19@osu.edu

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210-1442
      • Recruiting
      • The Ohio State University
      • Contact: Madison Kackley; Phone Number: 6142479650; Email: Kackley.19@osu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Other: 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).
Active Comparator: 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.	Dietary supplement: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Serum Progesterone Concentration (ng/mL)	To determine the effects of ketogenic diet and exogenous ketone supplementation on circulating reproductive hormone concentrations. Serum progesterone will be analyzed using standard immunoassay techniques (Quest Diagnostics panels and/or validated ELISA assays). Hormonal changes will be compared between baseline and post-intervention to assess improvements in reproductive axis regulation.	Baseline to 12 weeks
Change in Serum Estradiol Concentration (pg/mL)	To determine the effects of ketogenic diet and exogenous ketone supplementation on circulating reproductive hormone concentrations. Serum estradiol will be analyzed using commercially available immunoassay kits (Quest Diagnostics panels and/or validated ELISA assays). Hormonal changes will be compared between baseline and post-intervention to assess improvements in reproductive axis regulation.	Baseline to 12 weeks
Change in Serum Luteinizing Hormone Concentration (mIU/mL)	To determine the effects of ketogenic diet and exogenous ketone supplementation on circulating reproductive hormone concentrations. Serum luteinizing hormone (LH) will be analyzed using standard immunoassay techniques (Quest Diagnostics panels and/or validated ELISA assays). Hormonal changes will be compared between baseline and post-intervention to assess improvements in reproductive axis regulation.	Baseline to 12 weeks
Change in Serum Follicle Stimulating Hormone Concentrations (mIU/mL)	To determine the effects of ketogenic diet and exogenous ketone supplementation on circulating reproductive hormone concentrations. Serum follicle-stimulating hormone (FSH) will be analyzed using standard immunoassay techniques (Quest Diagnostics panels and/or validated ELISA assays). Hormonal changes will be compared between baseline and post-intervention to assess improvements in reproductive axis regulation.	Baseline to 12 weeks
Change in Daily Fasting BHB (mmol/L)	To assess changes in metabolic parameters including fasting β-hydroxybutyrate (BHB). Capillary ketones will be measured daily using KetoMojo handheld monitors.	Baseline to 12 weeks (Daily)
Change in Daily Fasting Glucose (mg/dL)	To assess changes in metabolic parameters including fasting glucose. Capillary glucose will be measured daily using KetoMojo handheld monitors.	Baseline to 12 weeks (Daily)
Change in Serum Insulin Concentration (µIU/mL)	To assess the effect of ketogenic diet and exogenous ketone supplementation on fasting insulin levels. Serum insulin will be measured at laboratory visits via immunoassay (Quest Diagnostics or validated ELISA). Mean change from baseline will be compared across groups.	Baseline to 12 weeks
Change in Serum Total Cholesterol Concentration (mg/dL)	To assess changes in fasting serum total cholesterol in response to ketogenic diet and exogenous ketone supplementation. Blood samples will be collected biweekly and analyzed using standard clinical chemistry methods (Quest Diagnostics). Mean change from baseline to 12 weeks will be reported.	Baseline to 12 weeks
Change in Serum Triglyceride Concentration (mg/dL)	To determine the effect of ketogenic diet and exogenous ketone supplementation on fasting triglyceride concentrations. Serum triglycerides will be measured via standard lipid panel. Mean change from baseline to 12 weeks will be compared across groups.	Baseline to 12 weeks
Change in Serum LDL Cholesterol Concentration (mg/dL)	To assess the effect of ketogenic diet and exogenous ketone supplementation on fasting low-density lipoprotein (LDL) cholesterol. Serum LDL will be measured via standard lipid panel (Quest Diagnostics). Mean change from baseline to post-intervention will be reported.	Baseline to 12 weeks
Change in Serum HDL Cholesterol Concentration (mg/dL)	To evaluate changes in fasting high-density lipoprotein (HDL) cholesterol following ketogenic diet or exogenous ketone supplementation. Serum HDL will be analyzed by clinical chemistry methods. Mean change from baseline to 12 weeks will be reported.	Baseline to 12 weeks

Collaborators and Investigators

• Sponsor: Ohio State University
• Investigators: Principal Investigator: Madison Kackley, PhD, Ohio State University

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: November 6, 2025
• First Submitted That Met QC Criteria: November 7, 2025
• First Posted (Actual): November 12, 2025

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: PCOS; Women's Health; Ketogenic Diet; Nutritional Ketosis; Reproductive Hormones; Metabolic Health; Ovarian Function; Exogenous Ketones
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Ovarian Cysts; Cysts; Polycystic Ovary Syndrome; Therapeutics; Diet, Food, and Nutrition; Physiological Phenomena; Nutritional Physiological Phenomena; Diet Therapy; Nutrition Therapy; Diet; Diet, Carbohydrate-Restricted; Diet, Ketogenic
• Other Study ID Numbers: 2023H0368

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: This is an early-stage pilot study focused on feasibility and exploratory outcomes. At this stage, individual participant data (IPD) will not be publicly shared until all analyses are complete and findings are published. De-identified aggregate data may be shared upon reasonable request following publication, in accordance with institutional and IRB policies. If a larger, follow-up trial is initiated, a formal data-sharing plan will be developed to align with NIH and ICMJE requirements.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No