Klinisk prövning på Sensorineural hörselnedsättning, Medfödd Cytomegalovirus, Cytomegalovirusinfektioner, Neonatal infektion, Virusinfektion - Kliniska prövningsregister

Studieöversikt

Status

Rekrytering

Betingelser

Detaljerad beskrivning

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.

Studietyp

Observationell

Inskrivning (Beräknad)

630

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studiekontakt

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

Studera Kontakt Backup

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

Studieorter

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

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

Barn

Tar emot friska volontärer

Ja

Testmetod

Icke-sannolikhetsprov

Studera befolkning

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.

Beskrivning

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

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

Antal grupper/kohorter

3

Kohorter och interventioner

Grupp / 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.

Vad mäter studien?

Primära resultatmått

Resultatmått	Åtgärdsbeskrivning	Tidsram
Differential protein expression associated with sequelae following congenital cytomegalovirus infection Tidsram: 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 Tidsram: 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).

Sekundära resultatmått

Resultatmått	Åtgärdsbeskrivning	Tidsram
Immune pathway enrichment based on proteomic and RNA expression profiles Tidsram: 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).

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Rigshospitalet, Denmark

Samarbetspartners

Statens Serum Institut

Utredare

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

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

21 april 2026

Primärt slutförande (Beräknad)

30 september 2026

Avslutad studie (Beräknad)

31 december 2026

Studieregistreringsdatum

Först inskickad

18 april 2023

Först inskickad som uppfyllde QC-kriterierna

4 juni 2026

Första postat (Faktisk)

9 juni 2026

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)