Klinische proef op Sensorineuraal gehoorverlies, Aangeboren Cytomegalovirus, Cytomegalovirusinfecties, Neonatale infectie, Virale infectie - Register voor klinische proeven

Studie Overzicht

Toestand

Werving

Conditie

Gedetailleerde beschrijving

Background:

Human cytomegalovirus (CMV) is one of the most common causes of congenital viral infection, leading to a significant number of children with permanent disabilities. It is recognized as the major infectious cause of sensorineural hearing loss (SNHL) and neurodevelopmental abnormalities in infants. Its pathogenesis is largely unknown due to the complex interplay between viral, maternal, placental, and child factors. In Western Europe the incidence is estimated to 0.5-0.7% of all live births. In Denmark there are 240-480 children born every year with CMV infection, but the incidence has not been studied since 1979. Among the congenitally infected infants, approximately 10% are estimated to have symptoms at birth, ranging from mild, such as petechiae, to severe, such as microcephaly. Approximately half of these symptomatic children develop permanent long-term disabilities, such as hearing loss, cognitive and motor developmental delay. Asymptomatic children are also at risk for CMV-related disabilities, and 10-15% will develop SNHL. SNHL after congenital CMV infection may be present at birth or occur later in childhood and therefore, a significant part of these will not be detected in time for diagnosis and appropriate treatment, e.g., ganciclovir within the first 30 days of life. At present, there is no reliable virological marker to determine which infants will develop sequelae.

Method:

A nationwide retrospective case-control study of all neonates with congenital CMV infection in Denmark from 2010 through 2025. DBS samples will be obtained from the Danish Neonatal Screening Biobank, Statens Serum Institut. Proteomic analyses and RNA sequencing will be performed at the Department for Congenital Disorders, Statens Serum Institut. Cases will be randomly assigned to a "Discovery cohort" and compared to a control group of neonates matched on gestational age, sex, birthweight and age at DBS sample collection.

Perspectives:

New molecular-based diagnostic tools may contribute to improve early diagnosis and treatment of infants with congenital CMV infection and potentially prevent development of sequelae. Additionally, understanding of the pathogenesis at a molecular level of severe disease manifestations of the disease, could form the basis for development of novel interventions for better prevention and treatment.

Studietype

Observationeel

Inschrijving (Geschat)

630

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

Naam: Kia Hee Schultz Dungu, MD
Telefoonnummer: +45 22645782
E-mail: kia.hee.schultz.dungu@regionh.dk

Studie Contact Back-up

Naam: Ulrikka Nygaard, Ass Prof PhD
Telefoonnummer: +45 35459761
E-mail: Ulrikka.Nygaard@regionh.dk

Studie Locaties

Denemarken
- - Copenhagen, Denemarken, 2100
    - Werving
    - Department of Paediatrics and Adolescent Medicine, Rigshospitalet
    - Contact:
      
      Kia Hee Schultz Dungu, MD
      
      Telefoonnummer: +45 22645782
      
      E-mail: kia.hee.schultz.dungu@regionh.dk
  - Copenhagen, Denemarken, 2300
    - Werving
    - Department of Congenital Disorders, Statens Serum Institut
    - Contact:
      
      David M Hougaard, D.Sc (med)
      
      Telefoonnummer: +45 32683544
      
      E-mail: dh@ssi.dk

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

Accepteert gezonde vrijwilligers

Ja

Bemonsteringsmethode

Niet-waarschijnlijkheidssteekproef

Studie Bevolking

The study population consists of children born in Denmark between January 1, 2010 and December 31, 2025 with available neonatal dried blood spot samples collected through the Danish National Newborn Screening Program. The study includes children with verified congenital cytomegalovirus (CMV) infection and matched controls without congenital CMV infection. Children with congenital CMV infection will be categorized according to the presence or absence of CMV-associated sequelae based on clinical follow-up data.

Beschrijving

Inclusion Criteria:

Children born between 1 January 2010 and 31 December 2025 with an available neonatal dried blood spot sample collected through the Danish National Newborn Screening Program.
Cases: children with verified congenital CMV infection, defined as a positive CMV PCR result on neonatal dried blood spot, blood, or urine collected within the neonatal period.
Controls: children without evidence of congenital CMV infection selected from the same newborn screening population and matched to cases on sex, gestational age, birthweight, and age at DBS sampling.

Exclusion Criteria:

DBS samples not approved for research use.
DBS samples with insufficient blood material for RNA expression profiling and/or proteomic analyses.
Samples with inadequate analytical quality for molecular or proteomic analyses.

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

Aantal groepen / cohorten

3

Cohorten en interventies

Groep / Cohort
Cases 300 children with symptomatic congenital CMV infection. Study procedures: Diagnostic/prognostic test and disease pathogenesis: Host RNA expression profiling by RNA sequencing and proteomic analyses. Cases will be randomly assigned to a "Discovery Cohort" for identification of diagnostic/prognostic RNA and proteomic profiles). Disease pathogenesis: Host RNA expression profiling by RNA sequencing and proteomic analyses will be performed to explore disease pathogenesis.
Control group 1 300 children without congenital CMV infection. Study procedures: Diagnostic/prognostic test and disease pathogenesis: Host RNA expression profiling by RNA sequencing and proteomic analyses. Cases will be randomly assigned to a "Discovery Cohort" for identification of diagnostic/prognostic RNA and proteomic profiles). Disease pathogenesis: Host RNA expression profiling by RNA sequencing and proteomic analyses will be performed to explore disease pathogenesis.
Control group 2 30 neonates with asymptomatic congenital CMV infection and no sequelae Study procedures: Diagnostic/prognostic test and disease pathogenesis: Host RNA expression profiling by RNA sequencing and proteomic analyses. Cases will be randomly assigned to a "Discovery Cohort" for identification of diagnostic/prognostic RNA and proteomic profiles). Disease pathogenesis: Host RNA expression profiling by RNA sequencing and proteomic analyses will be performed to explore disease pathogenesis.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat	Maatregel Beschrijving	Tijdsspanne
Differential protein expression associated with sequelae following congenital cytomegalovirus infection Tijdsspanne: At neonatal dried blood spot sampling (typically 2-3 days after birth).	Normalized protein expression levels measured by Olink proteomics in neonatal dried blood spot samples obtained at birth from children with congenital cytomegalovirus infection who subsequently developed sequelae compared with children who did not develop sequelae and healthy controls.	At neonatal dried blood spot sampling (typically 2-3 days after birth).
Differential host RNA expression associated with sequelae following congenital cytomegalovirus infection Tijdsspanne: At neonatal dried blood spot sampling (typically 2-3 days after birth).	Host RNA expression profiles measured in neonatal dried blood spot samples obtained at birth from children with congenital cytomegalovirus infection who subsequently developed sequelae compared with children who did not develop sequelae and healthy controls.	At neonatal dried blood spot sampling (typically 2-3 days after birth).

Secundaire uitkomstmaten

Uitkomstmaat	Maatregel Beschrijving	Tijdsspanne
Immune pathway enrichment based on proteomic and RNA expression profiles Tijdsspanne: At neonatal dried blood spot collection (typically 2-3 days after birth).	Immune and inflammatory pathways will be assessed by host RNA expression and normalized protein expression levels measured in neonatal dried blood spot samples. Pathway enrichment analyses will be used to identify biological pathways associated with congenital cytomegalovirus infection and subsequent sequelae. Exploratory comparisons will be made with previously published host RNA expression signatures related to infectious disease and immune responses.	At neonatal dried blood spot collection (typically 2-3 days after birth).

Medewerkers en onderzoekers

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

Sponsor

Rigshospitalet, Denmark

Medewerkers

Statens Serum Institut

Onderzoekers

Hoofdonderzoeker: Kia Hee Schultz Dungu, MD, Rigshospitalet, Denmark
Studie stoel: Ulrikka Nygaard, Ass Prof PhD, Rigshospitalet, Denmark

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 (Werkelijk)

21 april 2026

Primaire voltooiing (Geschat)

30 september 2026

Studie voltooiing (Geschat)

31 december 2026

Studieregistratiedata

Eerst ingediend

18 april 2023

Eerst ingediend dat voldeed aan de QC-criteria

4 juni 2026

Eerst geplaatst (Werkelijk)

9 juni 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)