Klinisk prøve på Sensorineuralt hørselstap, Medfødt cytomegalovirus, Cytomegalovirusinfeksjoner, Neonatal infeksjon, Virusinfeksjon - Klinisk prøveregister

Studieoversikt

Status

Rekruttering

Forhold

Detaljert beskrivelse

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

Observasjonsmessig

Registrering (Antatt)

630

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Navn: Kia Hee Schultz Dungu, MD
Telefonnummer: +45 22645782
E-post: kia.hee.schultz.dungu@regionh.dk

Studer Kontakt Backup

Navn: Ulrikka Nygaard, Ass Prof PhD
Telefonnummer: +45 35459761
E-post: Ulrikka.Nygaard@regionh.dk

Studiesteder

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

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

Barn

Tar imot friske frivillige

Ja

Prøvetakingsmetode

Ikke-sannsynlighetsprøve

Studiepopulasjon

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.

Beskrivelse

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.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

Antall grupper / kohorter

3

Kohorter og intervensjoner

Gruppe / Kohort
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.

Hva måler studien?

Primære resultatmål

Resultatmål	Tiltaksbeskrivelse	Tidsramme
Differential protein expression associated with sequelae following congenital cytomegalovirus infection Tidsramme: 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 Tidsramme: 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).

Sekundære resultatmål

Resultatmål	Tiltaksbeskrivelse	Tidsramme
Immune pathway enrichment based on proteomic and RNA expression profiles Tidsramme: 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).

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Rigshospitalet, Denmark

Samarbeidspartnere

Statens Serum Institut

Etterforskere

Hovedetterforsker: Kia Hee Schultz Dungu, MD, Rigshospitalet, Denmark
Studiestol: Ulrikka Nygaard, Ass Prof PhD, Rigshospitalet, Denmark

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

21. april 2026

Primær fullføring (Antatt)

30. september 2026

Studiet fullført (Antatt)

31. desember 2026

Datoer for studieregistrering

Først innsendt

18. april 2023

Først innsendt som oppfylte QC-kriteriene

4. juni 2026

Først lagt ut (Faktiske)

9. juni 2026

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)