Assessment of Metabolic Changes in Response to Glcuose Intake in Women With Polyendocrine Metabolic Ovarian Syndrome (PMOS)

NCT07687264 | Not Yet Recruiting

• 1 other identifier: MF26
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Polyendocrine metabolic ovarian syndrome (PMOS), previously known as polycystic ovary syndrome (PCOS), is a common endocrine and metabolic condition affecting women of reproductive age. It is associated with hormonal imbalances, irregular menstrual cycles, elevated androgen levels, and metabolic disturbances such as insulin resistance. These metabolic changes can increase the risk of type 2 diabetes and cardiovascular disease. Insulin resistance means that the body's cells respond less effectively to insulin, a hormone that regulates blood glucose. This leads to compensatory increases in insulin levels, which can further disrupt hormonal balance and contribute to the clinical features of PMOS. This study aims to investigate how the bodies of women with PMOS respond dynamically to glucose intake compared with women without PMOS. A standard clinical test, the oral glucose tolerance test (oGTT), will be used. Participants consume a glucose solution, and blood samples are collected before and two hours afterward. This procedure is routinely used in clinical practice. Women with PMOS will be compared with age- and body mass index (BMI)-matched control participants without PMOS. Blood and urine samples will be analyzed using advanced multi-omics technologies to measure proteins, metabolites, extracellular vesicles, and immune-related signals. The main objective is to understand how metabolic, hormonal, and immune pathways respond over time to a glucose challenge and whether these responses differ in PMOS. Special attention is given to inter-organ communication and systemic metabolic regulation. The study includes two visits. The first visit involves health assessments, questionnaires, and body composition measurements. The second visit includes the glucose tolerance test and blood sampling. In total, approximately 100 mL of blood will be collected across both visits. Participation is voluntary, and participants may withdraw at any time without affecting their medical care. The procedures involve minimal risk and consist of standard clinical methods. The results of this study may improve understanding of PMOS and contribute to better diagnostic and therapeutic strategies in the future.

Conditions

Insulinemic Response; Overweight (BMI > 25); PCOS (Polycystic Ovary Syndrome)

Keywords

PMOS; PCOS; oGTT; multi-omics; plasma proteomics; metabolomics; steroid hormones; inflammation; cytokines

Outcome Measures

Primary Outcomes (2)

• Change in Normalized Relative Plasma Metabolite Abundance From Baseline to 2 Hours Post-Glucose Ingestion

  Assessment of dynamic changes in circulating metabolites in response to a standardized oral glucose tolerance test (oGTT). Metabolomic profiling includes targeted and untargeted analyses of plasma metabolites involved in glucose metabolism, lipid metabolism, amino acid turnover, and energy homeostasis. Longitudinal changes between fasting state and post-glucose challenge will be compared between PMOS participants and age- and BMI-matched controls. The metabolomic response is used as a central readout of systemic metabolic flexibility.

  Baseline (fasting, Visit 2) and 2 hours post-glucose ingestion (Visit 2).

• Change in Normalized Relative Plasma Protein Abundance From Baseline to 2 Hours Post-Glucose Ingestion

  Quantification of dynamic changes in circulating plasma proteins in response to oGTT using nanoparticle-enhanced high-resolution proteomics. The analysis focuses on proteins involved in insulin signaling, inflammatory pathways, lipid metabolism, endocrine regulation, and inter-organ communication. Temporal protein abundance changes between fasting and post-glucose states will be assessed to characterize systemic proteomic adaptations and differences in metabolic flexibility between PMOS and controls.

  Baseline (fasting, Visit 2) and 2 hours post-glucose ingestion (Visit 2).

Secondary Outcomes (11)

• Change in oGTT-Derived Glucose and Insulin Response Indices From Baseline to 2 Hours Post-Glucose Ingestion

  Baseline and 2 hours post-glucose ingestion (Visit 2).

• Change in Concentration of Plasma Extracellular Vesicles From Baseline to 2 Hours Post-Glucose Ingestion

  Baseline and 2 hours post-glucose ingestion (Visit 2).

• Change in Median Diameter of Plasma Extracellular Vesicles From Baseline to 2 Hours Post-Glucose Ingestion

  Baseline and 2 hours post-glucose ingestion (Visit 2).

• Change in Normalized Relative Abundance of Extracellular Vesicle-Associated Proteins From Baseline to 2 Hours Post-Glucose Ingestion

  Baseline and 2 hours post-glucose ingestion (Visit 2).

• Change in Normalized Relative Abundance of Extracellular Vesicle-Associated Metabolites From Baseline to 2 Hours Post-Glucose Ingestion

  aseline and 2 hours post-glucose ingestion (Visit 2).

Study Arms (2)

PMOS group

EXPERIMENTAL

Woman diagnosed with PMOS, BMI 18.5-39.9 kg/m2

Procedure: Oral Clucose Tolerance Test (oGTT)

Control group

EXPERIMENTAL

Control participants will be selected to match PMOS group participants with respect to age (±3 years) and BMI (≤ ±2 kg/m²).

Procedure: Oral Clucose Tolerance Test (oGTT)

Interventions

Oral Clucose Tolerance Test (oGTT) PROCEDURE

After an overnight fasting period (≥8 hours), participants ingest a 75 g oral glucose solution. Venous blood samples are collected at predefined time points (fasting and typically 2 hours post-ingestion) to measure plasma glucose and insulin levels. The test evaluates whole-body glucose tolerance and insulin response under controlled metabolic conditions and is routinely used in clinical and research settings.

Control group; PMOS group

Eligibility Criteria

• Age: 18 Years - 35 Years
• Gender Eligibility Details: Eligibility is limited to participants whose gender identity corresponds to their biological sex (cisgender women). This restriction is necessary because the study investigates sex-specific physiological, hormonal, metabolic, and molecular responses, including analyses influenced by endogenous sex hormones and menstrual cycle characteristics.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age: 18-35 years
• Body weight (BMI): between BMI 18.5-39.9 kg/m2
• Ability to consent and to provide written informed consent
• CG: History of regular MCs (21 to 35 days) 3 months prior to study enrollment
• Oligo- or anovulation
• Clinical and/or biochemical signs of hyperandrogenism
• Polycystic ovaries on ultrasound (≥12 follicles per ovary measuring 2-9 mm in diameter and/or ovarian volume \>10 mL)

You may not qualify if:

• Use of systemic hormonal contraceptives within the last 3 months prior to study enrollment. Use of levonorgestrel-releasing intrauterine devices is permitted; all other hormonal contraceptive methods are excluded.
• CG: A clinically diagnosed or history of a menstrual disorder (e.g., polycystic ovarian syndrome (PCOS), premenstrual dysphoric disorder (PMDD) or amenorrhea)
• A clinically diagnosed mental disorder (e.g. major depression, anxiety disorder)
• history of epileptic seizure
• history of or current manic or psychotic episode
• existing/current eating disorders (bulimia nervosa, anorexia nervosa) within the past 5 years
• inability to communicate adequately in speech
• inability to follow instructions
• regular use of medication other than thyroxine
• alcohol consumption as equivalent doses of more than 12 g of pure alcohol per day
• vegan diet
• daily nicotine consumption
• currently or history of (regular) consumption of illegal drugs within the last year
• pregnancy or breastfeeding
• known diseases of the cardiovascular system

Sponsors & Collaborators

• University of Zurich: lead
• ETH Zurich: collaborator
• University Hospital, Bonn: collaborator

Study Sites (1)

University Hospital Zurich

Zurich, Canton of Zurich, 8091, Switzerland

Location

Related Publications (15)

• Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004 Jan;19(1):41-7. doi: 10.1093/humrep/deh098.

  PMID: 14688154 BACKGROUND

• Ferdosi S, Tangeysh B, Brown TR, Everley PA, Figa M, McLean M, Elgierari EM, Zhao X, Garcia VJ, Wang T, Chang MEK, Riedesel K, Chu J, Mahoney M, Xia H, O'Brien ES, Stolarczyk C, Harris D, Platt TL, Ma P, Goldberg M, Langer R, Flory MR, Benz R, Tao W, Cuevas JC, Batzoglou S, Blume JE, Siddiqui A, Hornburg D, Farokhzad OC. Engineered nanoparticles enable deep proteomics studies at scale by leveraging tunable nano-bio interactions. Proc Natl Acad Sci U S A. 2022 Mar 15;119(11):e2106053119. doi: 10.1073/pnas.2106053119. Epub 2022 Mar 11.

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• Mansournia MA, Jewell NP, Greenland S. Case-control matching: effects, misconceptions, and recommendations. Eur J Epidemiol. 2018 Jan;33(1):5-14. doi: 10.1007/s10654-017-0325-0. Epub 2017 Nov 3.

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• Tkach M, Thery C. Communication by Extracellular Vesicles: Where We Are and Where We Need to Go. Cell. 2016 Mar 10;164(6):1226-1232. doi: 10.1016/j.cell.2016.01.043.

  PMID: 26967288 BACKGROUND

• Chen R, Mias GI, Li-Pook-Than J, Jiang L, Lam HY, Chen R, Miriami E, Karczewski KJ, Hariharan M, Dewey FE, Cheng Y, Clark MJ, Im H, Habegger L, Balasubramanian S, O'Huallachain M, Dudley JT, Hillenmeyer S, Haraksingh R, Sharon D, Euskirchen G, Lacroute P, Bettinger K, Boyle AP, Kasowski M, Grubert F, Seki S, Garcia M, Whirl-Carrillo M, Gallardo M, Blasco MA, Greenberg PL, Snyder P, Klein TE, Altman RB, Butte AJ, Ashley EA, Gerstein M, Nadeau KC, Tang H, Snyder M. Personal omics profiling reveals dynamic molecular and medical phenotypes. Cell. 2012 Mar 16;148(6):1293-307. doi: 10.1016/j.cell.2012.02.009.

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• Ozer OF, Ibrahimoglu AZ, Gul AZ, Demirel M, Ates S, Taha HS, Ibrahimoglu M, Selek S. Mass spectrometry-based untargeted metabolomics study of polycystic ovary syndrome. J Ovarian Res. 2025 Nov 12;18(1):255. doi: 10.1186/s13048-025-01842-9.

  PMID: 41225634 BACKGROUND

• Stener-Victorin E, Eriksson G, Mohan Shrestha M, Rodriguez Paris V, Lu H, Banks J, Samad M, Perian C, Jude B, Engman V, Boi R, Nilsson E, Ling C, Nystrom J, Wernstedt Asterholm I, Turner N, Lanner J, Benrick A. Proteomic analysis shows decreased type I fibers and ectopic fat accumulation in skeletal muscle from women with PCOS. Elife. 2024 Jan 5;12:RP87592. doi: 10.7554/eLife.87592.

  PMID: 38180081 BACKGROUND

• Rajska A, Buszewska-Forajta M, Rachon D, Markuszewski MJ. Metabolomic Insight into Polycystic Ovary Syndrome-An Overview. Int J Mol Sci. 2020 Jul 9;21(14):4853. doi: 10.3390/ijms21144853.

  PMID: 32659951 BACKGROUND

• Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes. 1989 Sep;38(9):1165-74. doi: 10.2337/diab.38.9.1165.

  PMID: 2670645 BACKGROUND

• Petersen MC, Shulman GI. Mechanisms of Insulin Action and Insulin Resistance. Physiol Rev. 2018 Oct 1;98(4):2133-2223. doi: 10.1152/physrev.00063.2017.

  PMID: 30067154 BACKGROUND

• Henquin JC. Regulation of insulin secretion: a matter of phase control and amplitude modulation. Diabetologia. 2009 May;52(5):739-51. doi: 10.1007/s00125-009-1314-y. Epub 2009 Mar 14.

  PMID: 19288076 BACKGROUND

• Teede HJ, Khomami MB, Morman R, Laven JSE, Joham AE, Costello MF, Patil M, Rees DA, Berry L, Cree MG, Zhao H, Norman RJ, Dokras A, Piltonen T; Global Name Change Consortium. Polyendocrine metabolic ovarian syndrome, the new name for polycystic ovary syndrome: a multistep global consensus process. Lancet. 2026 Jun 6;407(10545):2329-2339. doi: 10.1016/S0140-6736(26)00717-8. Epub 2026 May 12.

  PMID: 42119588 BACKGROUND

• Gast KB, Tjeerdema N, Stijnen T, Smit JW, Dekkers OM. Insulin resistance and risk of incident cardiovascular events in adults without diabetes: meta-analysis. PLoS One. 2012;7(12):e52036. doi: 10.1371/journal.pone.0052036. Epub 2012 Dec 28.

  PMID: 23300589 BACKGROUND

• Stener-Victorin E, Teede H, Norman RJ, Legro R, Goodarzi MO, Dokras A, Laven J, Hoeger K, Piltonen TT. Polycystic ovary syndrome. Nat Rev Dis Primers. 2024 Apr 18;10(1):27. doi: 10.1038/s41572-024-00511-3.

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• March WA, Moore VM, Willson KJ, Phillips DI, Norman RJ, Davies MJ. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod. 2010 Feb;25(2):544-51. doi: 10.1093/humrep/dep399. Epub 2009 Nov 12.

  PMID: 19910321 BACKGROUND

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Overweight; Inflammation

Interventions

Glucose Tolerance Test

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; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques

Central Study Contacts

Jens Stepan, MD, PhD

CONTACT

+41 43 253 17 59; jens.stepan@usz.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2026
• First Posted: July 7, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): July 30, 2029
• Study Completion (Estimated): July 30, 2029
• Last Updated: July 7, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 12 months after publication until 10 years after publication
• Access Criteria: Upon reasonable request and approva

Locations

CH (1)