- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06337955
Non Primary HCMV Infection: Natural History and Immune Response
Evolution of HCMV Non-primary Infection and Host Immune Response in HCMV-seropositive Mothers of Children Attending Day-care Centers: An Observational Prospective Study
The goals of this observational study are: i) investigate the natural history of non-primary (i.e. reactivation and reinfection) HCMV infection in HCMV-seropositive Italian women and the relevant humoral and cell-mediated immune response; ii) reliably distinguish between reactivation and reinfection.
Prerequisite of the study is the availability of a maternal HCMV strain at baseline (original strain) to which subsequent strains detected during follow-up are compared in order to distinguish between reactivation (original strain) or reinfection (new strain).
To increase the likelihood of exposure to different HCMV strains, the study population is restricted to mothers of children attending day care centers.
Study Overview
Status
Conditions
Detailed Description
Eligible women will be identified and enrolled during pregnancy or at delivery. Consenting mothers will be tested for HCMV DNA in saliva, urine and vaginal swab at delivery and/or at the first scheduled post-partum visit (2-4 months after delivery). In addition, mothers and children will be tested for presence of HCMV DNA in milk and saliva samples, respectively.
A mother-child pair is considered HCMV-DNA positive and, therefore, suitable for continuing the study (i.e. the 12 months follow up after admission of the child to day care center) whenever viral DNA is detected in clinical samples of either the mother or the child or both. In fact, when viral DNA is undetectable in the mother but is present in the saliva of a 2-4 month old infant it can be reasonably assumed that the strain is of maternal origin.
The study does not require any modification in the normal mother-child relationship and participating mothers will be encouraged to behave normally. However, mothers will be asked to fill in a short questionnaire about basic behaviours in daily child care (i.e. frequency of hand washing, kissing of the infant, sharing of food...).
The following clinical samples will be collected from mothers and infants at indicated times (T):
T0. Delivery:
- mother: saliva, urine, vaginal swab, peripheral blood.
T1. 2-4 months after delivery:
- mother: saliva, urine, vaginal swab, milk, peripheral blood;
- infant: saliva swab.
T2. Admission of the infant to day care center:
- mother: saliva swab, urine, vaginal swab, peripheral blood;
- infant: saliva swab.
T3-T6. Every 3 months after admission of the infant for one year:
- mother: saliva swab, urine, vaginal swab, peripheral blood;
- infant: saliva swab.
Virological analyses:
- HCMV DNA detection and quantification in blood and body specimens;
- sequence analysis of selected variable viral genes and determination of strain(s) diversity (whole genome will also be sequenced when possible);
- HCMV isolation from collected specimens (when HCMV DNA shedding is detected).
Immunological analyses:
antibody response:
- IgG and IgM to whole HCMV antigens;
- IgG to glycoprotein complexes gHgLpUL128L, gHgLgO, gB;
- neutralizing (Nt) Ab blocking infection of epithelial/endothelial cells and fibroblasts.
T cell response:
- ex vivo cytokine (IFNgamma/IL-2) production;
- ex vivo proliferation after stimulation with HCMV antigens;
- differentiation state of HCMV specific T cells (CCR7, CD45RA, IL7R expression.
Questionnaire:
Participating mothers will also be invited to fill in a questionnaire concerning their daily habits in terms of caring for their children.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
PV
-
Pavia, PV, Italy, 27100
- Fondazione IRCCS Policlinico San Matteo
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Adult (≥18 years of age) HCMV IgG-positive, breast feeding* woman.
- Willingness to enroll the infant in a public or private day care facility with at least 5 attendees at ≤ 12 months of age.
- Willingness to participate in the study.
- In case of foreign origin, language skills sufficient to understand information material and give informed consent.
- Written informed consent. * Breast feeding not required in case of availability of HCMV DNA-positive samples from the mother and/or fetus and/or newborn.
Exclusion Criteria:
- Congenital or acquired immunodeficiency
- Immunosuppressive therapy
Study Plan
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
HCMV non-primary infection (reinfection or reactivation).
Time Frame: T3-T6: 3-6-9-12 months after admission of the infant to the day-care center.
|
HCMV non-primary infections will be calculated as the frequency of women with the presence of HCMV DNA in at least one of the body compartments examined (blood, saliva, urine, genital tract) at any time point.
Reinfections will be considered non-primary infections in which the HCMV strain detected is different from the strain detected at baseline.
|
T3-T6: 3-6-9-12 months after admission of the infant to the day-care center.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
HCMV-specific humoral and cell-mediated immune response during non-primary infection.
Time Frame: T3-T6: 3-6-9-12 months after admission of the infant to the day-care center.
|
Levels of IgG and IgM to whole HCMV antigens; titers of IgG specific for HCMV envelope glycoprotein complexes; neutralizing antibody titers; number, cytokine production and proliferation of T cells in response to HCMV.
|
T3-T6: 3-6-9-12 months after admission of the infant to the day-care center.
|
Maternal behaviours and occurrence of non-primary infection
Time Frame: T3-T6: 3-6-9-12 months after admission of the infant to the day-care center.
|
Data collected with the questionnaire and data on HCMV shedding by the own child will be compared between women with or without non-primary infections.
|
T3-T6: 3-6-9-12 months after admission of the infant to the day-care center.
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Potential use of saliva swabs for antibody determination.
Time Frame: T0: Enrollment.
|
HCMV-specific IgG in saliva.
|
T0: Enrollment.
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Daniele Lilleri, MD, Fondazione IRCCS Policlinico San Matteo
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 20170007596
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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