Biomarker Panel for PCOS-Associated Liver Steatosis in Adolescent Girls (COMPASS-pedPCOS)

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Диагностический тест Extended Serum Biomarker and Hormonal Panel
  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
• Диагностический тест Liver Elastography with Controlled Attenuation Parameter
  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.
• Генная терапия Targeted Genotyping of PNPLA3 rs738409 and HSD17B13 rs72613567
  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.

Первичные конечные точки

• Hepatic Steatosis Measured by Controlled Attenuation Parameter (CAP) [Срок оценки: Day 1 (single study visit)]
• Serum Fetuin-A Concentration [Срок оценки: Day 1 (single study visit)]
• Serum Fibroblast Growth Factor 21 (FGF-21) Concentration [Срок оценки: Day 1 (single study visit)]
• Serum Adiponectin Concentration [Срок оценки: Day 1 (single study visit)]
• Serum Visfatin Concentration [Срок оценки: Day 1 (single study visit)]

Вторичные конечные точки (4)

• Serum Soluble CD163 Concentration [Срок оценки: Day 1 (single study visit)]
• Serum Cytokeratin-18 M30 and M65 Concentrations [Срок оценки: Day 1 (single study visit)]
• Liver Stiffness Measurement [Срок оценки: Day 1 (single study visit)]
• Discriminatory Performance of the Biomarker Panel for Hepatic Steatosis [Срок оценки: Day 1 (single study visit)]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

Turkey (Türkiye) · 1 центр

• University of Health Sciences, Kayseri City Hospital — Kayseri

Публикации

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Идентификаторы

NCT: NCT07731373 · Etik C.D.No:1010 (Kayseri CH) · TÜSEB2026-A4-U ProjectNo55983

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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