Protein Biomarkers and Host RNA Expression Profiles in Congenital Cytomegalovirus Infection
Przegląd badań
Status
Szczegółowy opis
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.
Typ studiów
Zapisy (Szacowany)
Kontakty i lokalizacje
Kontakt w sprawie studiów
- Nazwa: Kia Hee Schultz Dungu, MD
- Numer telefonu: +45 22645782
- E-mail: kia.hee.schultz.dungu@regionh.dk
Kopia zapasowa kontaktu do badania
- Nazwa: Ulrikka Nygaard, Ass Prof PhD
- Numer telefonu: +45 35459761
- E-mail: Ulrikka.Nygaard@regionh.dk
Lokalizacje studiów
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Copenhagen, Dania, 2100
- Rekrutacyjny
- Department of Paediatrics and Adolescent Medicine, Rigshospitalet
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Kontakt:
- Kia Hee Schultz Dungu, MD
- Numer telefonu: +45 22645782
- E-mail: kia.hee.schultz.dungu@regionh.dk
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Copenhagen, Dania, 2300
- Rekrutacyjny
- Department of Congenital Disorders, Statens Serum Institut
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Kontakt:
- David M Hougaard, D.Sc (med)
- Numer telefonu: +45 32683544
- E-mail: dh@ssi.dk
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Kryteria uczestnictwa
Kryteria kwalifikacji
Wiek uprawniający do nauki
- Dziecko
Akceptuje zdrowych ochotników
Metoda próbkowania
Badana populacja
Opis
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.
Plan studiów
Jak projektuje się badanie?
Szczegóły projektu
Kohorty i interwencje
Grupa / Kohorta |
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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. |
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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. |
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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. |
Co mierzy badanie?
Podstawowe miary wyniku
Miara wyniku |
Opis środka |
Ramy czasowe |
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Differential protein expression associated with sequelae following congenital cytomegalovirus infection
Ramy czasowe: At neonatal dried blood spot sampling (typically 2-3 days after birth).
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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.
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At neonatal dried blood spot sampling (typically 2-3 days after birth).
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Differential host RNA expression associated with sequelae following congenital cytomegalovirus infection
Ramy czasowe: At neonatal dried blood spot sampling (typically 2-3 days after birth).
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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.
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At neonatal dried blood spot sampling (typically 2-3 days after birth).
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Miary wyników drugorzędnych
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
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Immune pathway enrichment based on proteomic and RNA expression profiles
Ramy czasowe: At neonatal dried blood spot collection (typically 2-3 days after birth).
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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.
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At neonatal dried blood spot collection (typically 2-3 days after birth).
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Współpracownicy i badacze
Sponsor
Współpracownicy
Śledczy
- Główny śledczy: Kia Hee Schultz Dungu, MD, Rigshospitalet, Denmark
- Krzesło do nauki: Ulrikka Nygaard, Ass Prof PhD, Rigshospitalet, Denmark
Daty zapisu na studia
Główne daty studiów
Rozpoczęcie studiów (Rzeczywisty)
Zakończenie podstawowe (Szacowany)
Ukończenie studiów (Szacowany)
Daty rejestracji na studia
Pierwszy przesłany
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy wysłany (Rzeczywisty)
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia weryfikacja
Więcej informacji
Terminy związane z tym badaniem
Dodatkowe istotne warunki MeSH
- Objawy neurologiczne
- Choroby Układu Nerwowego
- Infekcje
- Infekcje wirusami DNA
- Choroby otorynolaryngologiczne
- Zaburzenia czucia
- Choroby uszu
- Infekcje Herpesviridae
- Utrata słuchu
- Zaburzenia słuchu
- Stany patologiczne, oznaki i objawy
- Objawy i symptomy
- Choroby wirusowe
- Utrata słuchu, czuciowo-nerwowa
- Infekcje wirusem cytomegalii
Inne numery identyfikacyjne badania
- H-21009288-CMV
Plan dla danych uczestnika indywidualnego (IPD)
Planujesz udostępniać dane poszczególnych uczestników (IPD)?
Informacje o lekach i urządzeniach, dokumenty badawcze
Bada produkt leczniczy regulowany przez amerykańską FDA
Bada produkt urządzenia regulowany przez amerykańską FDA
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