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Non-Invasive Diagnostic Panel for MASLD in Children With Obesity (PedMASLD-Pilot)

29 juli 2026 bijgewerkt door: Agah Bahadır Öztürk,MD, Kayseri City Hospital

A Non-Invasive Diagnostic Panel for MASLD in Children With Obesity: Evaluation of a Multiparametric Biomarker Panel and Genetic Risk Score Using LASSO-Regularized Logistic Regression - The PedMASLD-MultiOmics Pilot Study

This prospective, single-center, two-group observational study evaluates a non-invasive multi-parameter diagnostic panel for metabolic dysfunction-associated steatotic liver disease (MASLD) in children with obesity. A total of 180 children aged 8 to 18 years with a body mass index at or above the 85th percentile for age and sex are planned for enrollment at a single tertiary pediatric center.

Each participant attends a single study visit comprising a fasting venous blood sample for serum biomarkers (cytokeratin-18 M30 and M65, fibroblast growth factor 21, retinol-binding protein 4, insulin-like growth factor binding protein 7, adiponectin, leptin, insulin, and routine biochemistry), abdominal ultrasonography with two-dimensional shear wave elastography, and genotyping of three MASLD-associated variants (PNPLA3 rs738409, TM6SF2 rs58542926, HSD17B13 rs72613567).

Participants are classified as MASLD-positive or MASLD-negative according to a guideline-based composite reference standard consisting of ultrasonographic steatosis grading and cardiometabolic risk factor criteria, assessed independently of the candidate index tests. The primary objective is to determine the discriminative performance, expressed as the area under the receiver operating characteristic curve, of a LASSO-regularized logistic regression model combining biomarker, elastography, and genetic predictors. No therapeutic intervention is assigned by the study protocol. Reporting will follow the STARD 2015 statement.

Studie Overzicht

Toestand

Nog niet aan het werven

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease of childhood and is closely associated with obesity. Liver biopsy, the histological reference standard, is not ethically acceptable as a routine screening tool in children because it requires general anaesthesia and carries procedural risk and sampling error. The currently used non-invasive screening tools, alanine aminotransferase and ultrasonography, have limited diagnostic accuracy when used alone. An accurate, non-invasive diagnostic approach for pediatric MASLD is therefore needed.

This single-center, prospective, two-group, exploratory pilot diagnostic classification study is conducted at Kayseri City Hospital, Kayseri, Türkiye. Children aged 8 to 18 years with a body mass index at or above the 85th percentile for age and sex, according to Turkish national growth references, are screened consecutively in the pediatric endocrinology outpatient clinic. Enrollment of 180 participants is planned, balanced by sex.

Each participant attends a single study visit of approximately three hours. After a 12-hour fast, a single venous blood sample is obtained for routine biochemistry, insulin, and the serum biomarker panel; serum and plasma aliquots are stored at -80 °C until batched analysis by enzyme-linked immunosorbent assay in duplicate with blinded internal controls. Abdominal ultrasonography is performed for hepatic steatosis grading, and liver stiffness is measured by two-dimensional shear wave elastography. A separate whole-blood sample is used for DNA isolation and genotyping of three MASLD-associated variants, from which a three-variant polygenic risk score is derived. Anthropometric measurements including waist circumference percentile, blood pressure, pubertal staging, and questionnaire-based nutritional and physical activity assessment are recorded at the same visit. No therapeutic intervention is assigned by the study protocol.

Participants are classified as MASLD-positive or MASLD-negative using a composite reference standard based on ultrasonographic steatosis grading together with cardiometabolic risk factor criteria, in accordance with current pediatric guidelines. To avoid incorporation bias, two-dimensional shear wave elastography is used only as a candidate predictor and does not contribute to the reference standard; reference standard assessment is performed blinded to biomarker and genotype results.

The analysis develops a LASSO-regularized logistic regression model combining serum biomarkers, liver stiffness, and the polygenic risk score, with internal validation by bootstrap resampling. Model discrimination is compared with alanine aminotransferase alone and with ultrasonography alone. Reporting will follow the STARD 2015 statement.

Studietype

Observationeel

Inschrijving (Geschat)

180

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Locaties

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Kind
  • Volwassen

Accepteert gezonde vrijwilligers

Nee

Bemonsteringsmethode

Niet-waarschijnlijkheidssteekproef

Studie Bevolking

Children aged 8 to 18 years with a body mass index at or above the 85th percentile for age and sex, screened consecutively in the pediatric endocrinology outpatient clinic of a single tertiary center in Kayseri, Türkiye. Participants are enrolled prospectively using consecutive non-probability sampling and are classified as MASLD-positive or MASLD-negative according to a composite reference standard.

Beschrijving

Inclusion Criteria:

  • Age 8 to 18 years.
  • Body mass index at or above the 85th percentile for age and sex according to Turkish national growth references.
  • Hepatic steatosis of grade 1 or higher on abdominal ultrasonography and/or alanine aminotransferase at or above the biology-based upper limit of normal (26 U/L for boys; 22 U/L for girls), or persistent alanine aminotransferase elevation at or above twice the upper limit of normal (50 U/L for boys; 44 U/L for girls).
  • At least one cardiometabolic risk factor.
  • Written informed consent provided by a parent or legal guardian, with simplified assent for children aged 8 to 11 years and standard assent for children aged 12 years and older.

Exclusion Criteria:

  • Viral hepatitis.
  • Autoimmune liver disease.
  • Wilson disease, alpha-1 antitrypsin deficiency, or hereditary hemochromatosis.
  • Use of hepatotoxic medication, including corticosteroids, methotrexate, valproate, amiodarone, or tamoxifen.
  • Fasting duration shorter than 12 hours.
  • Active infection, defined as C-reactive protein above 10 mg/L.
  • Untreated thyroid disorder, defined as thyroid-stimulating hormone below 0.5 or above 5.
  • Total parenteral nutrition.
  • Diabetic ketoacidosis.
  • Inability to obtain informed consent.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

Cohorten en interventies

Groep / Cohort
Interventie / Behandeling
Group 1 MASLD-Positive
MASLD-Positive - Children with obesity classified as having MASLD by the composite reference standard (ultrasonographic steatosis grading plus cardiometabolic risk factor criteria). All candidate index tests are performed.
Diagnostische toets: Non-Invasive Multi-Parameter Diagnostic Panel
All participants undergo the same set of index tests at a single study visit: a fasting venous blood sample for serum cytokeratin-18 M30 and M65, fibroblast growth factor 21, retinol-binding protein 4, insulin-like growth factor binding protein 7, adiponectin, leptin, insulin and routine biochemistry measured by enzyme-linked immunosorbent assay and standard laboratory methods; abdominal ultrasonography with two-dimensional shear wave elastography for liver stiffness; and genotyping of PNPLA3 rs738409, TM6SF2 rs58542926 and HSD17B13 rs72613567 for derivation of a three-variant polygenic risk score. These are observational measurements; no therapeutic intervention is administered.
Group 2 MASLD-Negative
MASLD-Negative - Children with obesity not meeting the composite reference standard for MASLD. All candidate index tests are performed.
Diagnostische toets: Non-Invasive Multi-Parameter Diagnostic Panel
All participants undergo the same set of index tests at a single study visit: a fasting venous blood sample for serum cytokeratin-18 M30 and M65, fibroblast growth factor 21, retinol-binding protein 4, insulin-like growth factor binding protein 7, adiponectin, leptin, insulin and routine biochemistry measured by enzyme-linked immunosorbent assay and standard laboratory methods; abdominal ultrasonography with two-dimensional shear wave elastography for liver stiffness; and genotyping of PNPLA3 rs738409, TM6SF2 rs58542926 and HSD17B13 rs72613567 for derivation of a three-variant polygenic risk score. These are observational measurements; no therapeutic intervention is administered.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Diagnostic Performance of the LASSO-Regularized Multi-Parameter Panel for MASLD
Tijdsspanne: Through study completion, an average of 12 months
Discriminative performance of a LASSO-regularized logistic regression model combining serum biomarkers (cytokeratin-18 M30, cytokeratin-18 M65, fibroblast growth factor 21, retinol-binding protein 4, insulin-like growth factor binding protein 7), homeostatic model assessment of insulin resistance, liver stiffness measured by two-dimensional shear wave elastography, and a three-variant polygenic risk score, for classifying participants against the composite reference standard for MASLD. Metric: area under the receiver operating characteristic curve with bootstrap-derived 95% confidence interval.
Through study completion, an average of 12 months

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Comparative Discrimination of the Panel Versus Alanine Aminotransferase Alone and Ultrasonography Alone
Tijdsspanne: Through study completion, an average of 12 months
Comparison of the area under the receiver operating characteristic curve of the multi-parameter panel with that of alanine aminotransferase alone and of ultrasonography alone for classification against the composite reference standard, using the DeLong test for correlated curves.
Through study completion, an average of 12 months
Serum Biomarker Concentrations in MASLD-Positive Versus MASLD-Negative Children With Obesity
Tijdsspanne: Day 1 (single study visit)
Comparison of serum concentrations of cytokeratin-18 M30 and M65, fibroblast growth factor 21, retinol-binding protein 4, insulin-like growth factor binding protein 7, adiponectin and leptin between participants classified as MASLD-positive and MASLD-negative. Units of measure as reported by the respective enzyme-linked immunosorbent assays.
Day 1 (single study visit)
Incremental Discriminative Value of Serum IGFBP7
Tijdsspanne: Through study completion, an average of 12 months
Incremental contribution of serum insulin-like growth factor binding protein 7 to the classification model, evaluated by change in the area under the receiver operating characteristic curve, the net reclassification improvement, and the integrated discrimination improvement.
Through study completion, an average of 12 months

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Kayseri City Hospital

Medewerkers

Presidency of the Health Institutes of Türkiye

Onderzoekers

  • Hoofdonderzoeker: Agah B ÖZTÜRK, MD, Kayseri City Hospital, Kayseri, Türkiye

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Geschat)

1 juli 2026

Primaire voltooiing (Geschat)

1 april 2027

Studie voltooiing (Geschat)

1 juni 2027

Studieregistratiedata

Eerst ingediend

22 juli 2026

Eerst ingediend dat voldeed aan de QC-criteria

24 juli 2026

Eerst geplaatst (Werkelijk)

28 juli 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

30 juli 2026

Laatste update ingediend die voldeed aan QC-criteria

29 juli 2026

Laatst geverifieerd

1 juli 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • Etik C.D.No:1009(Kayseri CH)
  • TUSEB-2026-A4-U-55859 (Andere identificatie: Health Institutes of Türkiye (TÜSEB))

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

JA

Beschrijving IPD-plan

De-identified individual participant data underlying the published results, including serum biomarker concentrations, anthropometric, clinical and laboratory variables, and derived index values, will be available from the principal investigator upon reasonable request. Individual genotype data will be shared only in aggregate or as derived polygenic risk scores, in accordance with the ethics approval and applicable data protection legislation. Data will be shared with qualified researchers whose proposed use has been approved and is consistent with the original ethics approval. A data-use agreement will be required.

IPD-tijdsbestek voor delen

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

IPD-toegangscriteria voor delen

Qualified researchers may request access by contacting the principal investigator. Requests will be evaluated for scientific merit and for consistency with the original ethics approval and the scope of participant consent. A data-use agreement must be executed before de-identified data are released.

IPD delen Ondersteunend informatietype

  • LEERPROTOCOOL
  • SAP
  • ICF

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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