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

NCT01251744 | Completed Results

• 1 other identifier: 113134
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 9

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.

Conditions

Infections, Cytomegalovirus; Cytomegalovirus Infections

Keywords

Pregnancy; Congenital; Cytomegalovirus infection

Outcome Measures

Primary Outcomes (41)

• Number of Subjects With Any Cytomegalovirus (CMV) Congenital Infection

  The CMV congenital infections were assessed in newborns and foetuses of subjects who had a confirmed primary CMV infection during pregnancy.

  At Month 0

• Number of Subjects With CMV Presence in the Urine

  Evidence of infection in urine was assessed by culture or by Polymerase Chain Reaction (PCR).

  Within 10 days post-delivery (Days 0-9)

• Number of Subjects With CMV Presence in the Amniotic Fluid

  Evidence of infection in the amniotic fluid was assessed by culture or by Polymerase Chain Reaction (PCR).

  Within 10 days post-delivery (Days 0-9)

• Evidence of CMV DNA or CMV Inclusions in Tissues of an Aborted or Stillborn Foetus

  Within 10 days post-delivery (Days 0-9)

• Number of CMV DNA Copies in Saliva, Urine, Blood or Vaginal Secretions

  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.

  At Month 0

• Number of CMV DNA Copies in Saliva, in Urine and in Blood or Vaginal Secretions

  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.

  At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)

• Descriptive Statistics of the Anti-CMV Immunoglobulin Type M (IgM) Status

  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.

  At Month 0

• Descriptive Statistics of the Anti-CMV IgM Status

  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.

  At Month 2

• Descriptive Statistics of the Anti-Cytomegalovirus (Anti-CMV) Immunoglobulin Type M (IgM) Status

  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.

  At Month 4

• Anti-CMV Immunoglobulin Type M (IgM) Status, Descriptive Statistics

  Anti-CMV IgM status was assessed by Enzyme-Linked Immunosorbent Assay \[ELISA\], with respect to positive and negative subjects.

  At Month 6

• Descriptive Statistics for the Anti-CMV IgM Status

  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.

  At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)

• Anti-glycoprotein B (gB) Immunoglobulin Type G (IgG) Antibody Concentrations

  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 greater than or equal to (≥) 54 EU/mL.

  At Month 0

• Anti-gB IgG Antibody Concentrations

  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 greater than or equal to (≥) 54 EU/mL.

  At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)

• Descriptive Statistics of the Anti-glycoprotein B (gB) Immunoglobulin Type G (IgG) Avidity Index

  The avidity index was calculated as the mean absorbance of reactions in which the immune complexes were exposed to urea divided by the mean absorbance of reactions in which the immune complexes were not exposed to urea, expressed as a percentage.

  At Month 0

• Descriptive Statistics of the Anti-gB IgG Avidity Index

  The avidity index was calculated as the mean absorbance of reactions in which the immune complexes were exposed to urea divided by the mean absorbance of reactions in which the immune complexes were not exposed to urea, expressed as a percentage.

  At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)

• CMV-specific Cluster of Differentiation 4 (CD4) T-cell Frequencies

  Descriptive statistics of the frequency of CMV-specific CD4 T cells expressing at least two markers among: cluster of differentiation 40 ligand (CD40L), interleukin-2 (IL-2), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), as assessed by Intracellular Cytokine Staining \[ICS\], by stimulating agent (among Human Cytomegalovirus \[HCMV\] immediate-early gene \[IE1\] antigen, HCMV glicoprotein B \[gB\] antigen, HCMV lysate antigen and HCMV pp65 antigen).

  At Month 0

• CMV-specific CD4 T-cell Frequencies

  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).

  At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)

• CMV-specific Cluster of Differentiation 8 (CD8) T-cell Frequencies

  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).

  At Month 0

• CMV-specific CD8 T-cell Frequencies

  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).

  At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)

• CMV-specific Proliferating Cluster of Differentiation (CD4) T Cells Frequencies

  Labelled cells were quantified by flow cytometry, by stimulating agent (among immediate-early gene \[IE1\] antigen, glicoprotein B \[gB\] antigen, CMV lysate antigen and CMV pp65 antigen).

  At Month 0

• CMV-specific Proliferating CD4 T Cells Frequencies

  Labelled cells were quantified by flow cytometry, by stimulating agent (among immediate-early gene \[IE1\] antigen, glicoprotein B \[gB\] antigen, CMV lysate antigen and CMV pp65 antigen). Note: Results were retrieved by subtracting the background without imputing the negative and zero values, this generated negative values.

  At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)

• Concentrations of Anti-CMV Tegument Protein Immunoglobulin G (IgG) Antibodies

  Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs), measured in units per milliliter (U/mL). Concentrations of antibodies were assessed by the Enzyme-Linked Immunosorbent Assay (ELISA) for a cut-off greater than or equal to (≥) 0.668 U/mL.

  At Day 0 = study entry

• Anti-CMV Tegument Protein Immunoglobulin G (IgG) Antibody Concentrations

  Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs), measured in units per milliliter (U/mL). Concentrations of antibodies were assessed by the Enzyme-Linked Immunosorbent Assay (ELISA) for a cut-off greater than or equal to (≥) 0.668 U/mL.

  At Month 2

• Concentrations of Anti-CMV Tegument Protein IgG Antibodies

  Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs), measured in units per milliliter (U/mL). Concentrations of antibodies were assessed by the Enzyme-Linked Immunosorbent Assay (ELISA) for a cut-off greater than or equal to (≥) 0.668 U/mL.

  At Month 4

• Anti-CMV Tegument Protein IgG Antibody Concentrations

  Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs), measured in units per milliliter (U/mL). Concentrations of antibodies were assessed by the Enzyme-Linked Immunosorbent Assay (ELISA) for a cut-off greater than or equal to (≥) 0.668 U/mL.

  At Month 6

• Concentrations of Anti-CMV IgG Antibodies

  Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs), measured in units per milliliter (U/mL). Concentrations of antibodies were assessed by the Enzyme-Linked Immunosorbent Assay (ELISA) for a cut-off greater than or equal to (≥) 0.668 U/mL.

  At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)

• Descriptive Statistics of the Anti-CMV Tegument Protein Globulin Type B (gB) Immunoglobulin G (IgG) Avidity, by Congenital Infection Status

  Avidity of anti-CMV tegument protein gB IgG was assessed by ELISA. The avidity index was calculated as the mean absorbance of reactions in which the immune complexes were exposed to urea divided by the mean absorbance of reactions in which the immune complexes were not exposed to urea, expressed as a percentage.

  At Day 0 = study entry

• Descriptive Statistics of the Anti-CMV Tegument Protein gB Immunoglobulin G (IgG) Avidity, by Congenital Infection Status

  Avidity of anti-CMV tegument protein gB IgG was assessed by ELISA. The avidity index was calculated as the mean absorbance of reactions in which the immune complexes were exposed to urea divided by the mean absorbance of reactions in which the immune complexes were not exposed to urea, expressed as a percentage.

  At Month 2

• Descriptive Statistics of the Anti-CMV Tegument Protein gB IgG Avidity, by Congenital Infection Status

  Avidity of anti-CMV tegument protein gB IgG was assessed by ELISA. The avidity index was calculated as the mean absorbance of reactions in which the immune complexes were exposed to urea divided by the mean absorbance of reactions in which the immune complexes were not exposed to urea, expressed as a percentage.

  At Month 4

• Descriptive Statistics of the Anti-CMV Tegument Protein Globulin Type B (gB) IgG Avidity, by Congenital Infection Status

  Avidity of anti-CMV tegument protein gB IgG was assessed by ELISA. The avidity index was calculated as the mean absorbance of reactions in which the immune complexes were exposed to urea divided by the mean absorbance of reactions in which the immune complexes were not exposed to urea, expressed as a percentage.

  At Month 6

• Anti-CMV Tegument Protein Globulin Type B (gB) Immunoglobulin G (IgG) Avidity Descriptive Statistics, by Congenital Infection Status

  Avidity of anti-CMV tegument protein gB IgG was assessed by ELISA. The avidity index was calculated as the mean absorbance of reactions in which the immune complexes were exposed to urea divided by the mean absorbance of reactions in which the immune complexes were not exposed to urea, expressed as a percentage.

  At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)

• Anti-CMV Antibody Titers, by Neutralisation Assay (Fibroblast)

  Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of ≥ 10 ED50.

  At Month 0

• Anti-CMV Antibody Titers, by Neutralisation Assay (Fibroblast)

  Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of ≥ 10 ED50.

  At Month 2

• Anti-CMV Antibody Titers, by Neutralisation Assay (Fibroblast)

  Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of ≥ 10 ED50.

  At Month 4

• Anti-CMV Antibody Titers, by Neutralisation Assay (Fibroblast)

  Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of ≥ 10 ED50.

  At Month 6

• Anti-CMV Antibody Titers, by Neutralisation Assay (Fibroblast)

  Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of ≥ 10 ED50.

  At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)

• Anti-CMV Antibody Titers, by Neutralisation Assay (Epithelial Cells)

  Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of ≥ 15 ED50.

  At Month 0

• Anti-CMV Antibody Titers, by Neutralisation Assay (Epithelial Cells)

  Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of ≥ 15 ED50.

  At Month 2

• Anti-CMV Antibody Titers, by Neutralisation Assay (Epithelial Cells)

  Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of ≥ 15 ED50.

  At Month 4

• Anti-CMV Antibody Titers, by Neutralisation Assay (Epithelial Cells)

  Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of ≥ 15 ED50.

  At Month 6

• Anti-CMV Antibody Titers, by Neutralisation Assay (Epithelial Cells)

  Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of ≥ 10 ED50.

  At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)

Study Arms (2)

CMV Mothers' Group

EXPERIMENTAL

Pregnant subjects with confirmed primary CMV infection.

Procedure: Blood sample; Procedure: Cord blood sample; Procedure: Saliva swab; Procedure: Urine sampling; Procedure: Vaginal swab

CMV Newborns' Group

EXPERIMENTAL

Offsprings of the CMV Mothers' Group, also tested for CMV infection, comprising infants that were live born.

Procedure: Blood sample; Procedure: Cord blood sample; Procedure: Saliva swab; Procedure: Urine sampling; Procedure: Vaginal swab

Interventions

Blood sample PROCEDURE

Blood sample at study entry, every two months during pregnancy, at pregnancy conclusion and one month after pregnancy conclusion.

CMV Mothers' Group; CMV Newborns' Group

Cord blood sample PROCEDURE

Cord blood sample taken at the time of delivery.

CMV Mothers' Group; CMV Newborns' Group

Saliva swab PROCEDURE

Saliva swab taken at study entry, every month during pregnancy, at pregnancy conclusion and one month after pregnancy conclusion.

CMV Mothers' Group; CMV Newborns' Group

Urine sampling PROCEDURE

Approximately 10 mL of urine will be sampled at study entry, every month during pregnancy, at pregnancy conclusion and one month after pregnancy conclusion.

CMV Mothers' Group; CMV Newborns' Group

Vaginal swab PROCEDURE

Vaginal swab taken at study entry, every month during pregnancy and one month after pregnancy conclusion.

CMV Mothers' Group; CMV Newborns' Group

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (9)

GSK Investigational Site

Brussels, 1000, Belgium

Location

GSK Investigational Site

Brussels, 1050, Belgium

Location

GSK Investigational Site

Brussels, 1070, Belgium

Location

GSK Investigational Site

Charleroi, 6000, Belgium

Location

GSK Investigational Site

La Louvière, 7100, Belgium

Location

GSK Investigational Site

Leuven, 3000, Belgium

Location

GSK Investigational Site

Liège, 4000, Belgium

Location

GSK Investigational Site

Mons, 7000, Belgium

Location

GSK Investigational Site

Wilrijk, 2610, Belgium

Location

Related Publications (2)

• Marchant A, Adali S, Alsdurf H, Bol V, Capelle X, De Schrevel N, Delroisse JM, Devlieger R, Dieussaert I, Donner C, Janssens M, Loquet P, Panackal AA, Seidl C, van den Berg RA, Paris R. Establishing Correlates of Maternal-Fetal Cytomegalovirus Transmission-One Step Closer Through Predictive Modeling. J Infect Dis. 2024 Dec 16;230(6):e1274-e1286. doi: 10.1093/infdis/jiae281.

  PMID: 38865084 DERIVED

• 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.

  PMID: 22865914 DERIVED

MeSH Terms

Conditions

Cytomegalovirus Infections

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2010
• First Posted: December 2, 2010
• Study Start: December 9, 2010
• Primary Completion: November 6, 2013
• Study Completion: June 17, 2015
• Last Updated: June 29, 2020
• Results First Posted: January 2, 2020

Record last verified: 2020-05

Locations

BE (9)