Polycystic Ovary Syndrome (PCOS)COMPASSpedPCOSNCT07731373
Biomarker Panel for PCOS-Associated Liver Steatosis in Adolescent Girls (COMPASS-pedPCOS)
An observational study of Polycystic Ovary Syndrome (PCOS) and Metabolic Dysfunction-Associated Steatotic Liver Disease, run by Kayseri City Hospital at 1 site in Turkey (Türkiye).
Trial 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. Read more about this study
- Who is it for?
- Ages 10 to 18 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Polycystic Ovary Syndrome (PCOS), Metabolic Dysfunction-Associated Steatotic Liver Disease, Pediatric Obesity
- What is being tested?
- Extended Serum Biomarker and Hormonal Panel and Targeted Genotyping of PNPLA3 rs738409 and HSD17B13 rs72613567
- How many people
- 150 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 1 Sep 2026to 1 Sep 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 to 18 years
- Women only
- Healthy volunteers accepted
- Child, Adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Turkey (Türkiye)1 site
University of Health Sciences, Kayseri City Hospital
Kayseri, 38080
Agah B ÖZTÜRK, Principal Investigator, Department of Pediatrics, MD, +90 352 315 77 00, agahbahadir.ozturk@sbu.edu.tr
About this study
Official title: COMPASS-PedPCOS: BMI-Independent Mechanistic Dissection of PCOS-Associated MASLD in Adolescent Girls With Obesity Using an Expanded Biomarker Panel - A Single-Center Pre-Pilot Clinical Study
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.
Read the detailed description
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition of childhood and is closely linked to obesity and insulin resistance. Polycystic ovary syndrome (PCOS) frequently co-occurs with obesity in adolescent girls, and hyperandrogenism has been proposed as an additional hepatic insult. Because obesity is a powerful confounder, the independent contribution of hyperandrogenism to hepatic steatosis in adolescents remains poorly defined.
This study will be conducted at the Departments of Pediatric, Departments of Pediatric Endocrinology, Pediatric Gastroenterology and Hepatology, Medical Biochemistry, Medical Genetics, and Pediatric Radiology of Kayseri City Hospital, Kayseri, Türkiye. Participants will be allocated to three predefined groups. Group 1 comprises girls with PCOS and obesity, diagnosed according to adolescent-adapted Rotterdam criteria requiring both hyperandrogenism and oligo-anovulation, with a body mass index at or above the 95th percentile. Group 2 comprises girls with obesity without features of PCOS, matched to Group 1 for age and body mass index. Group 3 comprises healthy normal-weight girls between the 5th and 84th body mass index percentiles.
The central comparison is Group 1 versus Group 2, which equalises adiposity and therefore isolates the contribution of hyperandrogenism. Hierarchical regression models will additionally adjust for body mass index z-score, homeostatic model assessment of insulin resistance, and free androgen index. Hepatic steatosis will be quantified by the controlled attenuation parameter obtained during vibration-controlled transient elastography; liver stiffness will be assessed by vibration-controlled transient elastography and two-dimensional shear wave elastography.
A single venous blood sample will be obtained at the study visit. Serum will be separated and stored at minus 80 degrees Celsius until batch analysis, and genomic DNA will be isolated for TaqMan single nucleotide polymorphism genotyping of PNPLA3 rs738409 and HSD17B13 rs72613567. All enzyme-linked immunosorbent assay kits will be procured as a single lot, and intra-assay and inter-assay coefficients of variation together with spike-recovery validation will be documented for each kit.
Data will be recorded in a REDCap electronic case report form in accordance with ALCOA+ principles. The study is exploratory and is designed to generate effect-size and variance estimates for a subsequent validation study. Reporting will follow the STROBE statement, and non-invasive diagnostic performance analyses will follow the STARD 2015 statement. The study is also referred to as COMPASS-PedPCOS in institutional, ethics committee and funding documents.
- Conditions
- Polycystic Ovary Syndrome (PCOS), Metabolic Dysfunction-Associated Steatotic Liver Disease, Pediatric Obesity, Hyperandrogenism, Insulin Resistance Syndrome
- Being tested
- Extended Serum Biomarker and Hormonal Panel, Liver Elastography with Controlled Attenuation Parameter, Targeted Genotyping of PNPLA3 rs738409 and HSD17B13 rs72613567
- Keywords
- HSD17B13, PNPLA3, 11-oxygenated androgens, GDF-15, sCD163, CK-18, visfatin, adiponectin, FGF-21, Fetuin-A, PCOS, adipokine, hepatokine, transient elastography, controlled attenuation parameter, hepatic steatosis
- Medical subject headings
- Polycystic Ovary Syndrome, Pediatric Obesity, Hyperandrogenism, Metabolic Syndrome, Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Extended Serum Biomarker and Hormonal PanelDiagnostic test
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.
Liver Elastography with Controlled Attenuation ParameterDiagnostic test
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.
Targeted Genotyping of PNPLA3 rs738409 and HSD17B13 rs72613567Genetic
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Diagnostic Test: Extended Serum Biomarker and Hormonal Panel; Diagnostic Test: Liver Elastography with Controlled Attenuation Parameter; Genetic: 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. Receives: Diagnostic Test: Extended Serum Biomarker and Hormonal Panel; Diagnostic Test: Liver Elastography with Controlled Attenuation Parameter; Genetic: 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. Receives: Diagnostic Test: Extended Serum Biomarker and Hormonal Panel; Diagnostic Test: Liver Elastography with Controlled Attenuation Parameter; Genetic: Targeted Genotyping of PNPLA3 rs738409 and HSD17B13 rs72613567 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 1 (single study visit)
Secondary outcomes (4)
Serum Soluble CD163 Concentration
Serum soluble CD163, a marker of macrophage activation, measured by enzyme-linked immunosorbent assay and compared across the three study groups; evaluated as a candidate mediator of the association between hyperandrogenism and hepatic steatosis. Unit of measure: ng/mL.
Measured: Day 1 (single study visit)
Serum Cytokeratin-18 M30 and M65 Concentrations
Serum cytokeratin-18 M30 (apoptotic fragment) and M65 (total cell death) measured by enzyme-linked immunosorbent assay and compared across the three study groups to characterise the mode of hepatocyte death. Unit of measure: U/L for each analyte.
Measured: Day 1 (single study visit)
Liver Stiffness Measurement
Liver stiffness assessed by vibration-controlled transient elastography and by two-dimensional shear wave elastography, compared across the three study groups. Unit of measure: kPa.
Measured: Day 1 (single study visit)
Discriminatory Performance of the Biomarker Panel for Hepatic Steatosis
Receiver operating characteristic analysis of individual biomarkers and of a composite preliminary risk score for the identification of hepatic steatosis. Measures include area under the receiver operating characteristic curve with 95% confidence intervals, sensitivity, and specificity at the Youden index.
Measured: Day 1 (single study visit)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2026
- Study start1 Sep 2026 (estimated)
- Primary completion30 Apr 2027 (estimated)
- Study completion1 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Polycystic Ovary Syndrome (PCOS)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kayseri City Hospital
- Sponsor type
- Other government
- Collaborators
- Presidency of the Health Institutes of Türkiye
- Responsible party
- Principal investigator, Agah Bahadır Öztürk,MD, Kayseri City Hospital
- Investigators
- Agah B ÖZTÜRK, MD, Principal investigator, Kayseri City Hospital, Kayseri, Türkiye
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07731373
- Sponsor's protocol ID
- Etik C.D.No:1010 (Kayseri CH)
- Other IDs
- TÜSEB2026-A4-U ProjectNo55983
- Acronym
- COMPASSpedPCOS
- Status last verified
- Jul 2026
- First submitted
- 22 Jul 2026
- Last updated
- 30 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 8970487Bossuyt 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.
PubMed 26511519von 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.
PubMed 18064739Vos 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.
PubMed 18852641Abul-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.
PubMed 29562163Romeo 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.
PubMed 18820647O'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.
PubMed 27901631Salva-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.
PubMed 31381969Pena 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.
PubMed 40069730Teede 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.
PubMed 37580861Rinella 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.
PubMed 37364790
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- COMPASS-PedPCOS: BMI-Independent Mechanistic Dissection of PCOS-Associated MASLD in Adolescent Girls With Obesity Using an Expanded Biomarker Panel - A Single-Center Pre-Pilot Clinical Study
- ClinicalTrials.gov ID
- NCT07731373
- Acronym / sponsor ID
- COMPASSpedPCOS / Etik C.D.No:1010 (Kayseri CH)
- Conditions
- Polycystic Ovary Syndrome (PCOS), Metabolic Dysfunction-Associated Steatotic Liver Disease, Pediatric Obesity, Hyperandrogenism, Insulin Resistance Syndrome
- Keywords
- HSD17B13, PNPLA3, 11-oxygenated androgens, GDF-15, sCD163, CK-18, visfatin, adiponectin
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Kayseri City HospitalOther government
- Collaborators
- Presidency of the Health Institutes of Türkiye
- Study start
- 1 Sep 2026 (estimated)
- Primary completion
- 30 Apr 2027 (estimated)
- Study completion
- 1 Sep 2027 (estimated)
- First posted
- 28 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition of childhood and is closely linked to obesity and insulin resistance. Polycystic ovary syndrome (PCOS) frequently co-occurs with obesity in adolescent girls, and hyperandrogenism has been proposed as an additional hepatic insult. Because obesity is a powerful confounder, the independent contribution of hyperandrogenism to hepatic steatosis in adolescents remains poorly defined.
This study will be conducted at the Departments of Pediatric, Departments of Pediatric Endocrinology, Pediatric Gastroenterology and Hepatology, Medical Biochemistry, Medical Genetics, and Pediatric Radiology of Kayseri City Hospital, Kayseri, Türkiye. Participants will be allocated to three predefined groups. Group 1 comprises girls with PCOS and obesity, diagnosed according to adolescent-adapted Rotterdam criteria requiring both hyperandrogenism and oligo-anovulation, with a body mass index at or above the 95th percentile. Group 2 comprises girls with obesity without features of PCOS, matched to Group 1 for age and body mass index. Group 3 comprises healthy normal-weight girls between the 5th and 84th body mass index percentiles.
The central comparison is Group 1 versus Group 2, which equalises adiposity and therefore isolates the contribution of hyperandrogenism. Hierarchical regression models will additionally adjust for body mass index z-score, homeostatic model assessment of insulin resistance, and free androgen index. Hepatic steatosis will be quantified by the controlled attenuation parameter obtained during vibration-controlled transient elastography; liver stiffness will be assessed by vibration-controlled transient elastography and two-dimensional shear wave elastography.
A single venous blood sample will be obtained at the study visit. Serum will be separated and stored at minus 80 degrees Celsius until batch analysis, and genomic DNA will be isolated for TaqMan single nucleotide polymorphism genotyping of PNPLA3 rs738409 and HSD17B13 rs72613567. All enzyme-linked immunosorbent assay kits will be procured as a single lot, and intra-assay and inter-assay coefficients of variation together with spike-recovery validation will be documented for each kit.
Data will be recorded in a REDCap electronic case report form in accordance with ALCOA+ principles. The study is exploratory and is designed to generate effect-size and variance estimates for a subsequent validation study. Reporting will follow the STROBE statement, and non-invasive diagnostic performance analyses will follow the STARD 2015 statement. The study is also referred to as COMPASS-PedPCOS in institutional, ethics committee and funding documents.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1 ''PCOS With Obesity'' | – | Diagnostic Test: Extended Serum Biomarker and Hormonal Panel, Diagnostic Test: Liver Elastography with Controlled Attenuation Parameter, Genetic: Targeted Genotyping of PNPLA3 rs738409 and HSD17B13 rs72613567PCOS 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. |
| Group 2 ''Obesity Control'' | – | Diagnostic Test: Extended Serum Biomarker and Hormonal Panel, Diagnostic Test: Liver Elastography with Controlled Attenuation Parameter, Genetic: Targeted Genotyping of PNPLA3 rs738409 and HSD17B13 rs72613567Obesity 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. |
| Group 3 ''Healthy Control'' | – | Diagnostic Test: Extended Serum Biomarker and Hormonal Panel, Diagnostic Test: Liver Elastography with Controlled Attenuation Parameter, Genetic: Targeted Genotyping of PNPLA3 rs738409 and HSD17B13 rs72613567Healthy 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. |
Who may qualify
- Ages
- 10 to 18 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- 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.
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Extended Serum Biomarker and Hormonal PanelA 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. | Diagnostic test | Group 1 ''PCOS With Obesity'', Group 2 ''Obesity Control'', Group 3 ''Healthy Control'' |
| Liver Elastography with Controlled Attenuation ParameterHepatic 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. | Diagnostic test | Group 1 ''PCOS With Obesity'', Group 2 ''Obesity Control'', Group 3 ''Healthy Control'' |
| Targeted Genotyping of PNPLA3 rs738409 and HSD17B13 rs72613567Genomic 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. | Genetic | Group 1 ''PCOS With Obesity'', Group 2 ''Obesity Control'', Group 3 ''Healthy Control'' |
Primary outcome
Hepatic Steatosis Measured by Controlled Attenuation Parameter (CAP)
Time frame: Day 1 (single study visit)
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.
Serum Fetuin-A Concentration
Time frame: Day 1 (single study visit)
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.
Serum Fibroblast Growth Factor 21 (FGF-21) Concentration
Time frame: Day 1 (single study visit)
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.
Serum Adiponectin Concentration
Time frame: Day 1 (single study visit)
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.
Serum Visfatin Concentration
Time frame: Day 1 (single study visit)
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.
4 secondary outcomes
Serum Soluble CD163 Concentration
Time frame: Day 1 (single study visit)
Serum Cytokeratin-18 M30 and M65 Concentrations
Time frame: Day 1 (single study visit)
Liver Stiffness Measurement
Time frame: Day 1 (single study visit)
Discriminatory Performance of the Biomarker Panel for Hepatic Steatosis
Time frame: Day 1 (single study visit)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2026.
- Results publication: PubMed 8970487Peduzzi 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.
- Results publication: PubMed 26511519Bossuyt 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.
- Results publication: PubMed 18064739von 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.
- Results publication: PubMed 18852641Vos 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.
- Results publication: PubMed 29562163Abul-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.
- Results publication: PubMed 18820647Romeo 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.
- Results publication: PubMed 27901631O'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.
- Results publication: PubMed 31381969Salva-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.
- Results publication: PubMed 40069730Pena 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.
- Results publication: PubMed 37580861Teede 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.
- Results publication: PubMed 37364790Rinella 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Agah B ÖZTÜRK, MD principal investigator
Kayseri City Hospital, Kayseri, Türkiye
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Polycystic Ovary Syndrome (PCOS) and Metabolic Dysfunction-Associated Steatotic Liver Disease, run by Kayseri City Hospital at 1 site in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 30 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Agah B Öztürk, MD, MD (+90 352 315 77 00, dr-agahoz@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hepatic Steatosis Measured by Controlled Attenuation Parameter (CAP) (time frame: Day 1 (single study visit)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07731373, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2026.