Study of the Transmission of Cytomegalovirus (CMV) Infection From Mother to Foetus

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

This study is designed to evaluate maternal virological and immunological parameters to determine their ability to predict congenital cytomegalovirus (CMV) infection. When a pregnant woman is infected with CMV, her immune system (which protects her from infection) is activated and the virus can be found in the woman's bodily fluids (blood, saliva, urine, vaginal secretions). The aim of this study is to find out if there is a link between either the pregnant woman's immune response or the presence of the virus in these bodily fluids and the child/foetus being infected with the virus.

Condition or disease	Intervention/treatment	Phase
Infections, Cytomegalovirus	Procedure: Blood sample; Procedure: Cord blood sample; Procedure: Saliva swab; Procedure: Urine sampling; Procedure: Vaginal swab	Not Applicable

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	159 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Other
Official Title:	Study of Maternal-foetal Cytomegalovirus (CMV) Transmission
Actual Study Start Date :	December 9, 2010
Actual Primary Completion Date :	November 6, 2013
Actual Study Completion Date :	June 17, 2015

Arms and Interventions

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Arm	Intervention/treatment
Experimental: CMV Mothers' Group; Pregnant subjects with confirmed primary CMV infection.	Procedure: Blood sample; Blood sample at study entry, every two months during pregnancy, at pregnancy conclusion and one month after pregnancy conclusion. Procedure: Cord blood sample; Cord blood sample taken at the time of delivery. Procedure: Saliva swab; Saliva swab taken at study entry, every month during pregnancy, at pregnancy conclusion and one month after pregnancy conclusion. Procedure: Urine sampling; Approximately 10 mL of urine will be sampled at study entry, every month during pregnancy, at pregnancy conclusion and one month after pregnancy conclusion. Procedure: Vaginal swab; Vaginal swab taken at study entry, every month during pregnancy and one month after pregnancy conclusion.
Experimental: CMV Infant Group; Offspring of the CMV Mothers' Group, also tested for CMV infection.	Procedure: Blood sample; Blood sample at study entry, every two months during pregnancy, at pregnancy conclusion and one month after pregnancy conclusion. Procedure: Cord blood sample; Cord blood sample taken at the time of delivery. Procedure: Saliva swab; Saliva swab taken at study entry, every month during pregnancy, at pregnancy conclusion and one month after pregnancy conclusion. Procedure: Urine sampling; Approximately 10 mL of urine will be sampled at study entry, every month during pregnancy, at pregnancy conclusion and one month after pregnancy conclusion. Procedure: Vaginal swab; Vaginal swab taken at study entry, every month during pregnancy and one month after pregnancy conclusion.

Outcome Measures

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Primary Outcome Measures :

1. Number of subjects with any CMV congenital infection [ Time Frame: At Day 0 ]
   The CMV congenital infections were assessed in newborns and foetuses of subjects who had a confirmed primary CMV infection during pregnancy.
2. Number of newborns with CMV presence in the urine [ Time Frame: Within 10 days post-delivery (Days 0-9) ]
   Evidence of infection in urine was assessed by culture or by Polymerase Chain Reaction (PCR).
3. Number of newborns with CMV presence in the amniotic fluid [ Time Frame: Within 10 days post-delivery (Days 0-9) ]
   Evidence of infection in the amniotic fluid was assessed by culture or by Polymerase Chain Reaction (PCR).
4. Number of pregnant subjects with evidence of CMV in saliva, urine, blood or vaginal secretions [ Time Frame: At Day 0 ]
   The assessment focused on the presence of CMV DNA copies (by Quantitative Polymerase Chain Reaction [qPCR]) in saliva, urine, blood and vaginal secretions every month from study entry to, and including, pregnancy conclusion.
5. Number of pregnant subjects with evidence of CMV in saliva, urine, blood or vaginal secretions [ Time Frame: At pregnancy conclusion ]
   The assessment focused on the presence of CMV DNA copies (by Quantitative Polymerase Chain Reaction [qPCR]) in saliva, urine and blood every month from study entry to, and including, pregnancy conclusion. No vaginal mucus results were available.
6. Descriptive statistics of the anti-CMV Immunoglobulin type M (IgM) status [ Time Frame: At Day 0 ]
   Anti-CMV IgM status was assessed by Enzyme-Linked Immunosorbent Assay [ELISA], with respect to positive and negative subjects. Grey Zone = optical density zone within 20% of cut-off value. When an optical density is within this grey zone, sample testing is repeated to confirm the result.
7. Descriptive statistics of the anti-CMV Immunoglobulin type M (IgM) status [ Time Frame: At Month 2 ]
   Anti-CMV IgM status was assessed by Enzyme-Linked Immunosorbent Assay [ELISA], with respect to positive and negative subjects. Grey Zone = optical density zone within 20% of cut-off value. When an optical density is within this grey zone, sample testing is repeated to confirm the result.
8. Descriptive statistics of the anti-CMV Immunoglobulin type M (IgM) status [ Time Frame: At Month 4 ]
   Anti-CMV IgM status was assessed by Enzyme-Linked Immunosorbent Assay [ELISA], with respect to positive and negative subjects. Grey Zone = optical density zone within 20% of cut-off value. When an optical density is within this grey zone, sample testing is repeated to confirm the result.
9. Descriptive statistics of the anti-CMV Immunoglobulin type M (IgM) status [ Time Frame: At Month 6 ]
   Anti-CMV IgM status was assessed by Enzyme-Linked Immunosorbent Assay [ELISA], with respect to positive and negative subjects.
10. Descriptive statistics of the anti-CMV Immunoglobulin type M (IgM) status [ Time Frame: At pregnancy conclusion ]
    Anti-CMV IgM status was assessed by Enzyme-Linked Immunosorbent Assay [ELISA], with respect to positive and negative subjects. Grey Zone = optical density zone within 20% of cut-off value. When an optical density is within this grey zone, sample testing is repeated to confirm the result.
11. Anti-CMV antibody titers [ Time Frame: Every two months from study entry to, and including, pregnancy conclusion ]
    As assessed by neutralisation assay. At the time of writing this summary, (re)development of CMV micro-neutralization assays is still ongoing. Results will be added when they become available
12. Anti-glycoprotein B (gB) immunoglobulin type G (IgG) antibody concentrations [ Time Frame: At Day 0 ]
    Anti-gB IgG concentrations were assessed by ELISA, presented as geometric mean concentrations and expressed in ELISA units per milliliter (EU/mL). The cut-off value was 54 EU/mL.
13. Anti-glycoprotein B (gB) immunoglobulin type G (IgG) antibody concentrations [ Time Frame: At pregnancy conclusion ]
    Anti-gB IgG concentrations were assessed by ELISA, presented as geometric mean concentrations (GMCs) and expressed in ELISA units per milliliter (EU/mL). The cut-off value was 54 EU/mL.
14. Descriptive statistics of the anti-glycoprotein B (gB) immunoglobulin type G (IgG) avidity index [ Time Frame: At Day 0 ]
    As assessed by ELISA.
15. Descriptive statistics of the anti-glycoprotein B (gB) immunoglobulin type G (IgG) avidity index [ Time Frame: At pregnancy conclusion ]
    As assessed by ELISA.
16. Anti-CMV tegument protein IgG antibody titres [ Time Frame: Every two months from study entry to, and including, pregnancy conclusion ]
    As assessed by ELISA.
17. Anti-CMV tegument protein IgG avidity index [ Time Frame: Every two months from study entry to, and including, pregnancy conclusion ]
    As assessed by ELISA
18. CMV-specific cluster of differentiation 4 (CD4) T-cell frequencies [ Time Frame: At Day 0 ]
    Descriptive statistics of the frequency of CMV-specific CD4 T cells expressing at least two markers among CD40L, IL-2, IFNg, TNFa, as assessed by Intracellular Cytokine Staining [ICS], by stimulating agent (among immediate-early gene [IE1] antigen, glicoprotein B [gB] antigen, CMV lysate antigen and CMV pp65 antigen).
19. CMV-specific cluster of differentiation 4 (CD4) T-cell frequencies [ Time Frame: At pregnancy conclusion ]
    Descriptive statistics of the frequency of CMV-specific CD4 T cells expressing at least two markers among CD40L, IL-2, IFNg, TNFa, as assessed by Intracellular Cytokine Staining [ICS], by stimulating agent (among immediate-early gene [IE1] antigen, glicoprotein B [gB] antigen, CMV lysate antigen and CMV pp65 antigen).
20. CMV-specific cluster of differentiation 8 (CD8) T-cell frequencies [ Time Frame: At Day 0 ]
    Descriptive statistics of the frequency of CMV-specific CD8 T cells expressing at least two markers among CD40L, IL-2, IFNg, TNFa, as assessed by Intracellular Cytokine Staining [ICS], by stimulating agent (among immediate-early gene [IE1] antigen, glicoprotein B [gB] antigen, CMV lysate antigen and CMV pp65 antigen).
21. CMV-specific cluster of differentiation 8 (CD8) T-cell frequencies [ Time Frame: At pregnancy conclusion ]
    Descriptive statistics of the frequency of CMV-specific CD8 T cells expressing at least two markers among CD40L, IL-2, IFNg, TNFa, as assessed by Intracellular Cytokine Staining [ICS], by stimulating agent (among immediate-early gene [IE1] antigen, glicoprotein B [gB] antigen, CMV lysate antigen and CMV pp65 antigen).
22. CMV-specific proliferating CD4 T cells frequencies [ Time Frame: At Day 0 ]
    As assessed by ICS, by stimulating agent (among immediate-early gene [IE1] antigen, glicoprotein B [gB] antigen, CMV lysate antigen and CMV pp65 antigen).
23. CMV-specific proliferating CD4 T cells frequencies [ Time Frame: At pregnancy conclusion ]
    As assessed by ICS, by stimulating agent (among immediate-early gene [IE1] antigen, glicoprotein B [gB] antigen, CMV lysate antigen and CMV pp65 antigen)

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Subjects who the investigator believes that they can and will comply with the requirements of the protocol .
• A pregnant female, 18 years of age or older at the time of study enrolment.
• Women with confirmed primary CMV infection.
• Written informed consent obtained from the subject.

Exclusion Criteria:

• Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to study entry.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational pharmaceutical product.
• Previous vaccination against CMV infection.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history or physical examination
• Major congenital defects, serious chronic illness or organ transplantation.
• Administration of immunoglobulins and/or any blood products within the three months preceding study enrolment or during the pregnancy.
• Documented Human immunodeficiency virus (HIV)-positive subject.
• Gestational age of more than 34 weeks, as determined by foetal ultrasound.

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

Belgium
GSK Investigational Site
Brussels, Belgium, 1000
GSK Investigational Site
Bruxelles, Belgium, 1050
GSK Investigational Site
Bruxelles, Belgium, 1070
GSK Investigational Site
Charleroi, Belgium, 6000
GSK Investigational Site
La Louvière, Belgium, 7100
GSK Investigational Site
Leuven, Belgium, 3000
GSK Investigational Site
Liège, Belgium, 4000
GSK Investigational Site
Mons, Belgium, 7000
GSK Investigational Site
Wilrijk, Belgium, 2610

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:	GSK Clinical Trials	GlaxoSmithKline

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Antoine P, Olislagers V, Huygens A, Lecomte S, Liesnard C, Donner C, Marchant A. Functional exhaustion of CD4+ T lymphocytes during primary cytomegalovirus infection. J Immunol. 2012 Sep 1;189(5):2665-72. doi: 10.4049/jimmunol.1101165. Epub 2012 Aug 3.

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT01251744 History of Changes
Other Study ID Numbers:	113134
First Posted:	December 2, 2010
Last Update Posted:	May 30, 2017
Last Verified:	May 2017

Keywords provided by GlaxoSmithKline:

Pregnancy; Congenital; Cytomegalovirus infection

Additional relevant MeSH terms:

Infection; Communicable Diseases; Cytomegalovirus Infections	Herpesviridae Infections; DNA Virus Infections; Virus Diseases