NCT07731373

Brief Summary

This single-center, prospective, observational, cross-sectional mechanistic pilot study will evaluate whether polycystic ovary syndrome (PCOS) contributes to hepatic steatosis in adolescent girls independently of adiposity. A total of 150 girls aged 10-18 years will be enrolled into three groups of 50: girls with PCOS and obesity, age- and body mass index-matched girls with obesity but without PCOS, and healthy normal-weight girls. Each participant will undergo a single evaluation comprising anthropometry, clinical and biochemical phenotyping, transient elastography with controlled attenuation parameter and two-dimensional shear wave elastography, and a single venous blood sample. An extended biomarker panel will be measured by enzyme-linked immunosorbent assay (Fetuin-A, fibroblast growth factor 21, adiponectin, visfatin, cytokeratin-18 M30 and M65, soluble CD163, growth differentiation factor 15, 11-ketotestosterone, and 11beta-hydroxyandrostenedione), together with liquid chromatography-tandem mass spectrometry measurement of testosterone and sex hormone-binding globulin, and genotyping of PNPLA3 rs738409 and HSD17B13 rs72613567. The primary objective is to compare hepatic steatosis and the hepatokine/adipokine profile between the PCOS with obesity group and the adiposity-matched obesity control group, adjusting for body mass index z-score, insulin resistance, and free androgen index. No therapeutic intervention is assigned by the study protocol.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
150

participants targeted

Target at P50-P75 for all trials

Timeline
12mo left

Started Sep 2026

Shorter than P25 for all trials

Geographic Reach
1 country

1 active site

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 22, 2026

Completed
6 days until next milestone

First Posted

Study publicly available on registry

July 28, 2026

Completed
1 month until next milestone

Study Start

First participant enrolled

September 1, 2026

Expected
8 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 30, 2027

4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2027

Last Updated

July 30, 2026

Status Verified

July 1, 2026

Enrollment Period

8 months

First QC Date

July 22, 2026

Last Update Submit

July 29, 2026

Conditions

Keywords

HSD17B13PNPLA311-oxygenated androgensGDF-15sCD163CK-18visfatinadiponectinFGF-21Fetuin-APCOSadipokinehepatokinetransient elastographycontrolled attenuation parameterhepatic steatosis

Outcome Measures

Primary Outcomes (5)

  • Hepatic Steatosis Measured by Controlled Attenuation Parameter (CAP)

    Controlled attenuation parameter obtained during vibration-controlled transient elastography, compared between girls with PCOS and obesity and adiposity-matched girls with obesity, and across all three study groups, with adjustment for body mass index z-score, homeostatic model assessment of insulin resistance, and free androgen index. Unit of measure: dB/m.

    Day 1 (single study visit)

  • Serum Fetuin-A Concentration

    Serum Fetuin-A measured by enzyme-linked immunosorbent assay and compared across the three study groups with adjustment for body mass index z-score, homeostatic model assessment of insulin resistance, and free androgen index. Unit of measure: µg/mL.

    Day 1 (single study visit)

  • Serum Fibroblast Growth Factor 21 (FGF-21) Concentration

    Serum FGF-21 measured by enzyme-linked immunosorbent assay and compared across the three study groups with adjustment for body mass index z-score, homeostatic model assessment of insulin resistance, and free androgen index. Unit of measure: pg/mL.

    Day 1 (single study visit)

  • Serum Adiponectin Concentration

    Serum adiponectin measured by enzyme-linked immunosorbent assay and compared across the three study groups with adjustment for body mass index z-score, homeostatic model assessment of insulin resistance, and free androgen index. Unit of measure: µg/mL.

    Day 1 (single study visit)

  • Serum Visfatin Concentration

    Serum visfatin measured by enzyme-linked immunosorbent assay and compared across the three study groups with adjustment for body mass index z-score, homeostatic model assessment of insulin resistance, and free androgen index. Unit of measure: ng/mL.

    Day 1 (single study visit)

Secondary Outcomes (4)

  • Serum Soluble CD163 Concentration

    Day 1 (single study visit)

  • Serum Cytokeratin-18 M30 and M65 Concentrations

    Day 1 (single study visit)

  • Liver Stiffness Measurement

    Day 1 (single study visit)

  • Discriminatory Performance of the Biomarker Panel for Hepatic Steatosis

    Day 1 (single study visit)

Other Outcomes (3)

  • Serum Growth Differentiation Factor 15 (GDF-15) Concentration

    Day 1 (single study visit)

  • Serum 11-Oxygenated Androgen Concentrations

    Day 1 (single study visit)

  • PNPLA3 rs738409 and HSD17B13 rs72613567 Genotype Distribution and Gene-Gene Interaction

    Day 1 (single study visit)

Study Arms (3)

Group 1 ''PCOS With Obesity''

PCOS With Obesity (n=50) - Girls aged 10-18 years meeting adolescent-adapted Rotterdam criteria (both hyperandrogenism and oligo-anovulation required) with body mass index at or above the 95th percentile.

Diagnostic Test: Extended Serum Biomarker and Hormonal PanelDiagnostic Test: Liver Elastography with Controlled Attenuation ParameterGenetic: Targeted Genotyping of PNPLA3 rs738409 and HSD17B13 rs72613567

Group 2 ''Obesity Control''

Obesity Control (n=50) - Girls with body mass index at or above the 95th percentile without features of PCOS, matched to Group 1 for age and body mass index.

Diagnostic Test: Extended Serum Biomarker and Hormonal PanelDiagnostic Test: Liver Elastography with Controlled Attenuation ParameterGenetic: Targeted Genotyping of PNPLA3 rs738409 and HSD17B13 rs72613567

Group 3 ''Healthy Control''

Healthy Control (n=50) - Girls aged 10-18 years meeting adolescent, Healthy normal-weight girls (body mass index 5th-84th percentile) without chronic disease, hyperandrogenism, or menstrual irregularity.

Diagnostic Test: Extended Serum Biomarker and Hormonal PanelDiagnostic Test: Liver Elastography with Controlled Attenuation ParameterGenetic: Targeted Genotyping of PNPLA3 rs738409 and HSD17B13 rs72613567

Interventions

A single fasting venous blood sample is obtained at the study visit. Enzyme-linked immunosorbent assay measurement of Fetuin-A, fibroblast growth factor 21, adiponectin, visfatin, cytokeratin-18 M30, cytokeratin-18 M65, soluble CD163, growth differentiation factor 15, 11-ketotestosterone and 11beta-hydroxyandrostenedione is performed. Total testosterone and sex hormone-binding globulin are measured by liquid chromatography-tandem mass spectrometry. Routine biochemistry and hormonal profiling are performed from the same sample. Observational only; no therapeutic agent is administered.

Group 1 ''PCOS With Obesity''Group 2 ''Obesity Control''Group 3 ''Healthy Control''

Hepatic steatosis and liver stiffness are assessed non-invasively at the same study visit. Vibration-controlled transient elastography with controlled attenuation parameter yields attenuation (dB/m) and stiffness (kPa) values; two-dimensional shear wave elastography provides an independent stiffness estimate. Predefined validity criteria are applied to all acquisitions. No sedation, contrast agent or ionizing radiation is used; the procedure is observational.

Group 1 ''PCOS With Obesity''Group 2 ''Obesity Control''Group 3 ''Healthy Control''

Genomic DNA is isolated from the same single venous blood sample; no additional venipuncture is required. TaqMan allelic discrimination assays are used for genotyping of PNPLA3 rs738409 and HSD17B13 rs72613567. Genotype call rate and Hardy-Weinberg equilibrium are reported. Genotyping is performed for research purposes only; results are not used to guide clinical management.

Group 1 ''PCOS With Obesity''Group 2 ''Obesity Control''Group 3 ''Healthy Control''

Eligibility Criteria

Age10 Years - 18 Years
Sexfemale
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64)
Sampling MethodNon-Probability Sample
Study Population

Adolescent girls aged 10 to 18 years presenting to the Departments of Pediatric Endocrinology and Pediatric Gastroenterology and Hepatology of Kayseri City Hospital, Kayseri, Türkiye. The study population comprises girls with polycystic ovary syndrome and obesity, girls with obesity without polycystic ovary syndrome matched for age and body mass index, and healthy normal-weight girls. Participants will be enrolled prospectively by consecutive sampling of eligible admissions.

You may qualify if:

  • Female, aged 10 to 18 years, with written informed consent from a parent or legal guardian and written assent from the child.
  • Group 1 (PCOS with obesity): both hyperandrogenism and oligo-anovulation required, based on adolescent-adapted Rotterdam criteria; body mass index at or above the 95th percentile.
  • Group 2 (Obesity control): body mass index at or above the 95th percentile, without features of PCOS, matched to Group 1 for age and body mass index.
  • Group 3 (Healthy control): healthy normal-weight girls (body mass index between the 5th and 84th percentile) without chronic disease, hyperandrogenism, or menstrual irregularity.

You may not qualify if:

  • Known acute or chronic liver disease (including viral, autoimmune, or Wilson disease) or use of hepatotoxic medication.
  • Endocrine disorders or secondary hyperandrogenism, including Cushing syndrome, hypothyroidism, uncontrolled diabetes mellitus, congenital adrenal hyperplasia, androgen-secreting tumour, or hyperprolactinaemia.
  • Syndromic or monogenic obesity (including Prader-Willi syndrome, Bardet-Biedl syndrome, Alström syndrome, MC4R or LEP variants) or a known genetic disorder.
  • Use of relevant or hepatotoxic medication within the preceding three months, including corticosteroids, metformin, oral contraceptives, valproic acid, or antiandrogens.
  • Pregnancy or regular alcohol use.
  • Refusal of consent or assent.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Health Sciences, Kayseri City Hospital

Kayseri, 38080, Turkey (Türkiye)

Location

Related Publications (11)

  • Peduzzi P, Concato J, Kemper E, Holford TR, Feinstein AR. A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol. 1996 Dec;49(12):1373-9. doi: 10.1016/s0895-4356(96)00236-3.

  • Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig L, Lijmer JG, Moher D, Rennie D, de Vet HC, Kressel HY, Rifai N, Golub RM, Altman DG, Hooft L, Korevaar DA, Cohen JF; STARD Group. STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. BMJ. 2015 Oct 28;351:h5527. doi: 10.1136/bmj.h5527.

  • von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007 Oct 20;370(9596):1453-7. doi: 10.1016/S0140-6736(07)61602-X.

  • Vos MB, Barve S, Joshi-Barve S, Carew JD, Whitington PF, McClain CJ. Cytokeratin 18, a marker of cell death, is increased in children with suspected nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr. 2008 Oct;47(4):481-5. doi: 10.1097/MPG.0b013e31817e2bfb.

  • Abul-Husn NS, Cheng X, Li AH, Xin Y, Schurmann C, Stevis P, Liu Y, Kozlitina J, Stender S, Wood GC, Stepanchick AN, Still MD, McCarthy S, O'Dushlaine C, Packer JS, Balasubramanian S, Gosalia N, Esopi D, Kim SY, Mukherjee S, Lopez AE, Fuller ED, Penn J, Chu X, Luo JZ, Mirshahi UL, Carey DJ, Still CD, Feldman MD, Small A, Damrauer SM, Rader DJ, Zambrowicz B, Olson W, Murphy AJ, Borecki IB, Shuldiner AR, Reid JG, Overton JD, Yancopoulos GD, Hobbs HH, Cohen JC, Gottesman O, Teslovich TM, Baras A, Mirshahi T, Gromada J, Dewey FE. A Protein-Truncating HSD17B13 Variant and Protection from Chronic Liver Disease. N Engl J Med. 2018 Mar 22;378(12):1096-1106. doi: 10.1056/NEJMoa1712191.

  • Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio LA, Boerwinkle E, Cohen JC, Hobbs HH. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008 Dec;40(12):1461-5. doi: 10.1038/ng.257. Epub 2008 Sep 25.

  • O'Reilly MW, Kempegowda P, Jenkinson C, Taylor AE, Quanson JL, Storbeck KH, Arlt W. 11-Oxygenated C19 Steroids Are the Predominant Androgens in Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2017 Mar 1;102(3):840-848. doi: 10.1210/jc.2016-3285.

  • Salva-Pastor N, Chavez-Tapia NC, Uribe M, Nuno-Lambarri N. Understanding the association of polycystic ovary syndrome and non-alcoholic fatty liver disease. J Steroid Biochem Mol Biol. 2019 Nov;194:105445. doi: 10.1016/j.jsbmb.2019.105445. Epub 2019 Aug 2.

  • Pena AS, Witchel SF, Boivin J, Burgert TS, Ee C, Hoeger KM, Lujan ME, Mousa A, Oberfield S, Tay CT, Teede H. International evidence-based recommendations for polycystic ovary syndrome in adolescents. BMC Med. 2025 Mar 11;23(1):151. doi: 10.1186/s12916-025-03901-w.

  • Teede HJ, Tay CT, Laven JJE, Dokras A, Moran LJ, Piltonen TT, Costello MF, Boivin J, Redman LM, Boyle JA, Norman RJ, Mousa A, Joham AE; International PCOS Network. Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Eur J Endocrinol. 2023 Aug 2;189(2):G43-G64. doi: 10.1093/ejendo/lvad096.

  • Rinella ME, Lazarus JV, Ratziu V, Francque SM, Sanyal AJ, Kanwal F, Romero D, Abdelmalek MF, Anstee QM, Arab JP, Arrese M, Bataller R, Beuers U, Boursier J, Bugianesi E, Byrne CD, Castro Narro GE, Chowdhury A, Cortez-Pinto H, Cryer DR, Cusi K, El-Kassas M, Klein S, Eskridge W, Fan J, Gawrieh S, Guy CD, Harrison SA, Kim SU, Koot BG, Korenjak M, Kowdley KV, Lacaille F, Loomba R, Mitchell-Thain R, Morgan TR, Powell EE, Roden M, Romero-Gomez M, Silva M, Singh SP, Sookoian SC, Spearman CW, Tiniakos D, Valenti L, Vos MB, Wong VW, Xanthakos S, Yilmaz Y, Younossi Z, Hobbs A, Villota-Rivas M, Newsome PN; NAFLD Nomenclature consensus group. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol. 2023 Dec;79(6):1542-1556. doi: 10.1016/j.jhep.2023.06.003. Epub 2023 Jun 24.

Biospecimen

Retention: SAMPLES WITH DNA

Serum for biomarker analysis and genomic DNA isolated from peripheral whole blood for targeted genotyping. Serum is stored at minus 80 degrees Celsius until batch analysis.

MeSH Terms

Conditions

Polycystic Ovary SyndromePediatric ObesityHyperandrogenismMetabolic SyndromeFatty Liver

Condition Hierarchy (Ancestors)

Ovarian CystsCystsNeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital DiseasesGonadal DisordersEndocrine System DiseasesObesityOverweightOvernutritionNutrition DisordersNutritional and Metabolic DiseasesBody WeightSigns and SymptomsPathological Conditions, Signs and Symptoms46, XX Disorders of Sex DevelopmentDisorders of Sex DevelopmentUrogenital AbnormalitiesAdrenogenital SyndromeMale Urogenital DiseasesCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesInsulin ResistanceHyperinsulinismGlucose Metabolism DisordersMetabolic DiseasesLiver DiseasesDigestive System Diseases

Study Officials

  • Agah B ÖZTÜRK, MD

    Kayseri City Hospital, Kayseri, Türkiye

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Agah B Öztürk, MD, MD

CONTACT

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER GOV
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator, Department of Pediatrics

Study Record Dates

First Submitted

July 22, 2026

First Posted

July 28, 2026

Study Start (Estimated)

September 1, 2026

Primary Completion (Estimated)

April 30, 2027

Study Completion (Estimated)

September 1, 2027

Last Updated

July 30, 2026

Record last verified: 2026-07

Data Sharing

IPD Sharing
Will share

De-identified individual participant data underlying the published results, including clinical, anthropometric, biochemical, biomarker, and imaging variables, will be available from the principal investigator upon reasonable request. Individual-level genotype data will be shared only in aggregate form, or in de-identified individual-level form where explicitly permitted by the participant consent and the ethics approval, in accordance with applicable national legislation on special categories of personal data. Requests will be evaluated for scientific merit and consistency with the original ethics approval, and a data-use agreement will be required.

Shared Documents
STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
Time Frame
Data will become available after publication of the main results and will remain available for 5 years thereafter, upon reasonable request to the principal investigator.
Access Criteria
Qualified researchers from recognised academic institutions may request access by contacting the principal investigator with a methodologically sound proposal. Requests will be reviewed by the study team for scientific merit and for consistency with the original ethics approval and participant consent. A signed data-use agreement is required before any de-identified data are released.

Locations