Neonatal Herpes Simplex InfectionNCT05226949
Host RNA Expression Profiles and Protein Biomarkers in Neonatal Herpes Simplex Virus Infection
An observational study of Neonatal Herpes Simplex Infection and Neonatal HSV Infection, run by Copenhagen University Hospital, Rigshospitalet at 2 sites in Denmark.
Trial summary
This study seeks to identify and test host RNA expression profiles in context to protein biomarkers in dried blood spot samples as novel diagnostic markers of neonatal herpes simplex virus infection and to improve the understanding of the pathogenesis of the disease. Read more about this study
- Who is it for?
- Ages 0 to 28 days
- Conditions the study is for
- Neonatal Herpes Simplex Infection, Neonatal HSV Infection, Neonatal Infection
- How many people
- 159 participants
- Where
- 2 sitesDenmark
- Study dates
- 1 Jan 2022to 30 Apr 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 28 days
- All sexes
- No healthy volunteers
- Child
Study population: Newborns aged 0-28 days with verified HSV infection in Denmark from 2010 through 2019.
Who may be able to join
- cases of newborns aged 0-28 days with verified HSV infection (positive HSV PCR in blood, cerebrospinal fluid and/or swab sample)
- controls of newborns without infection matched on gestational age, sex and birthweight
Who cannot join
- dried blood spot samples that are not allowed to be used for research
- dried blood spots samples containing insufficient amount of blood for research
Trial locations and contacts
2 sites in 1 country.
Denmark2 sites
Department of Paediatrics and Adolescent Medicine, Rigshospitalet
Copenhagen, 2100
Department of Congenital Disorders, Statens Serum Institut
Copenhagen, 2300
About this study
This study seeks to identify and test host RNA expression profiles in context to protein biomarkers in dried blood spot samples as novel diagnostic markers of neonatal herpes simplex virus infection and to improve the understanding of the pathogenesis of the disease.
Read the detailed description
Background:
Herpes Simplex Virus (HSV) infection in newborns is uncommon but can be devastating and is associated with significant morbidity and mortality. The diagnosis of neonatal HSV infection is challenging because maternal genital herpes often is asymptomatic and the clinical presentation in newborns can be nonspecific, especially in the early disease stages. This results in late diagnosis and potentially terrible consequences for the newborn. The reason why some newborns develop severe disease due to HSV infection is unknown. It has been suggested that immunologic differences in early infancy are the key to further advances. Host RNA expression profiling, transcriptomics, of the host response to infections has shown great potential as clinical tool for diagnostics and for unveiling molecular disease mechanisms. As previously shown, reliable host RNA expression data can be obtained from neonatal dried blood spot (DBS) samples by RNA-sequencing. Proteomic analysis has the potential to simultaneously identify hundreds of protein biomarkers and immune cell populations allowing for detailed mapping of disease immunological pathways.
Method:
A nationwide retrospective case-control study of all newborns with HSV infection in Denmark from 2010 through 2019. DBS samples will be obtained from the Danish Neonatal Screening Biobank, Statens Serum Institut. RNA sequencing and proteomic analyses will be performed at the Danish Center for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institut. Cases will be randomly assigned to a "Discovery cohort" and compared to a control group of newborns matched on gestational age, sex and birthweight will be included.
Time frame:
Sample identification/recruiting: January 1st to January 31st 2022. Sample analysis (RNA sequencing and proteomic analysis): February 1st to April 30th 2022.
Perspectives:
New molecular-based diagnostic tools complementary to conventional methods may improve early diagnosis of neonatal HSV infections and lead to optimised management. In addition, 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.
- Conditions
- Neonatal Herpes Simplex Infection, Neonatal HSV Infection, Neonatal Infection, Newborn; Infection, Herpes Simplex Virus Infection, Neonatal Sepsis
- Medical subject headings
- Neonatal herpes, Infections, Herpes Simplex, Neonatal Sepsis, Perinatal Death, Virus Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Cases | 54 newborns with neonatal HSV infection. Interventions: Diagnostic test and disease pathogenesis: Host RNA expression profiling by RNA sequencing and proteomic analyses. Cases will be randomly assigned to a "Discovery Cohort" (identification of diagnostic RNA and proteomic profiles). | |
| Controls | 108 newborns without infection. Interventions: Diagnostic test and disease pathogenesis: Host RNA expression profiling by RNA sequencing and proteomic analyses. Controls will be randomly assigned to a "Discovery Cohort" (identification of diagnostic RNA and proteomic profiles). |
What is being measured
The primary outcome is the main question the study is designed to answer.
Host RNA expression and proteomic profiles
To identify specific host RNA expression and proteomic profiles in dried blood spot samples from newborns with HSV infection
Measured: Admission, age 0-28 days
Secondary outcomes (2)
Disease pathogenesis
Mapping of disease immunological pathways by simultaneous host RNA expression profiling and proteomic analysis
Measured: Admission, age 0-28 days
Application of known host RNA profiles
To test host RNA profiles published in other studies, e.g. based on the genes IFI44L and FAM89A
Measured: Admission, age 0-28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2022
- Study start1 Jan 2022
- Primary completion28 Feb 2022
- Study completion30 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neonatal Herpes Simplex InfectionStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 159 participants (actual)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Collaborators
- Statens Serum Institut
- Responsible party
- Principal investigator, Kia Hee Schultz Dungu, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Kia Hee Schultz Dungu, MD, Principal investigator, Copenhagen University Hospital, RigshospitaletUlrikka Nygaard, Ass Prof PhD, Study chair, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05226949
- Sponsor's protocol ID
- H-21009288-HSV
- Status last verified
- Dec 2022
- First submitted
- 27 Jan 2022
- Last updated
- 28 Dec 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Host RNA Expression Profiles and Protein Biomarkers in Neonatal Herpes Simplex Virus Infection
- ClinicalTrials.gov ID
- NCT05226949
- Acronym / sponsor ID
- H-21009288-HSV
- Conditions
- Neonatal Herpes Simplex Infection, Neonatal HSV Infection, Neonatal Infection, Newborn; Infection, Herpes Simplex Virus Infection, Neonatal Sepsis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 159 participants (actual)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Collaborators
- Statens Serum Institut
- Study start
- 1 Jan 2022 (actual)
- Primary completion
- 28 Feb 2022 (actual)
- Study completion
- 30 Apr 2022 (actual)
- First posted
- 7 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study seeks to identify and test host RNA expression profiles in context to protein biomarkers in dried blood spot samples as novel diagnostic markers of neonatal herpes simplex virus infection and to improve the understanding of the pathogenesis of the disease.
Detailed description
Background:
Herpes Simplex Virus (HSV) infection in newborns is uncommon but can be devastating and is associated with significant morbidity and mortality. The diagnosis of neonatal HSV infection is challenging because maternal genital herpes often is asymptomatic and the clinical presentation in newborns can be nonspecific, especially in the early disease stages. This results in late diagnosis and potentially terrible consequences for the newborn. The reason why some newborns develop severe disease due to HSV infection is unknown. It has been suggested that immunologic differences in early infancy are the key to further advances. Host RNA expression profiling, transcriptomics, of the host response to infections has shown great potential as clinical tool for diagnostics and for unveiling molecular disease mechanisms. As previously shown, reliable host RNA expression data can be obtained from neonatal dried blood spot (DBS) samples by RNA-sequencing. Proteomic analysis has the potential to simultaneously identify hundreds of protein biomarkers and immune cell populations allowing for detailed mapping of disease immunological pathways.
Method:
A nationwide retrospective case-control study of all newborns with HSV infection in Denmark from 2010 through 2019. DBS samples will be obtained from the Danish Neonatal Screening Biobank, Statens Serum Institut. RNA sequencing and proteomic analyses will be performed at the Danish Center for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institut. Cases will be randomly assigned to a "Discovery cohort" and compared to a control group of newborns matched on gestational age, sex and birthweight will be included.
Time frame:
Sample identification/recruiting: January 1st to January 31st 2022. Sample analysis (RNA sequencing and proteomic analysis): February 1st to April 30th 2022.
Perspectives:
New molecular-based diagnostic tools complementary to conventional methods may improve early diagnosis of neonatal HSV infections and lead to optimised management. In addition, 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.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cases | – | –54 newborns with neonatal HSV infection. Interventions: Diagnostic test and disease pathogenesis: Host RNA expression profiling by RNA sequencing and proteomic analyses. Cases will be randomly assigned to a "Discovery Cohort" (identification of diagnostic RNA and proteomic profiles). |
| Controls | – | –108 newborns without infection. Interventions: Diagnostic test and disease pathogenesis: Host RNA expression profiling by RNA sequencing and proteomic analyses. Controls will be randomly assigned to a "Discovery Cohort" (identification of diagnostic RNA and proteomic profiles). |
Who may qualify
- Ages
- 0 to 28 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Newborns aged 0-28 days with verified HSV infection in Denmark from 2010 through 2019.
Key inclusion criteria (2 listed)
- cases of newborns aged 0-28 days with verified HSV infection (positive HSV PCR in blood, cerebrospinal fluid and/or swab sample)
- controls of newborns without infection matched on gestational age, sex and birthweight
Key exclusion criteria (2 listed)
- dried blood spot samples that are not allowed to be used for research
- dried blood spots samples containing insufficient amount of blood for research
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Host RNA expression and proteomic profiles
Time frame: Admission, age 0-28 days
To identify specific host RNA expression and proteomic profiles in dried blood spot samples from newborns with HSV infection
2 secondary outcomes
Disease pathogenesis
Time frame: Admission, age 0-28 days
Application of known host RNA profiles
Time frame: Admission, age 0-28 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2022.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kia Hee Schultz Dungu, MD principal investigator
Copenhagen University Hospital, Rigshospitalet
Ulrikka Nygaard, Ass Prof PhD study chair
Copenhagen University Hospital, Rigshospitalet
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Neonatal Herpes Simplex Infection and Neonatal HSV Infection, run by Copenhagen University Hospital, Rigshospitalet at 2 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Host RNA expression and proteomic profiles (time frame: Admission, age 0-28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Dec 2022.