Cytomegalovirus Shedding Characteristics in Pregnant Women

Study Overview
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Brief Summary
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The cCHIPS study is a feasibility study for larger scale multi-centre studies and is designed as a single-centre observational cohort, longitudinal, natural history study. The overarching aim of this study is to evaluate the feasibility of performing larger scale, multi-centre studies to evaluate the relationship between CMV shedding in pregnancy with congenital CMV (cCMV). There is no randomisation involved in this study and all participants will perform the same study procedures and receive treatment as usual. The primary (main) objective is to evaluate the prevalence (percentage of occurrence) of CMV shedding in saliva, urine and vaginal secretions of CMV seropositive women throughout pregnancy. The secondary objectives are to evaluate the quantity of CMV shedding in saliva, urine and vaginal secretions of CMV seropositive women throughout pregnancy, to compare the prevalence and quantity of CMV shedding in CMV seropositive women between different sources of shedding (saliva, urine or vaginal secretions) and different gestational stages, to identify risk factors for CMV shedding in CMV seropositive pregnant women, to evaluate the acceptability of the study procedures to the participating pregnant women, to evaluate the proportion of women approached who are recruited into the study and who are completing the study, and to evaluate the relationship between CMV specific cell mediated immunity (a type of immune protection following exposure to CMV) and CMV shedding in CMV seropositive pregnant women. The tertiary objective is to compare the evaluation of CMV specific T cell immune responses (a type of CMV specific cell mediated immunity) between the two commercially available CMV-specific T cell immune response assays which are QuantiFERON-CMV and CMV-ELISPOT assays. This study will aim to recruit 200 pregnant women. This study will be undertaken in parallel with a separate study called RACE-FIT (REC reference number 18/SC/0360, IRAS ID 239977), which will have ethical approval to screen pregnant women with children less than 4 years of age booked for their antenatal care at St George's Hospital, London, identified during the antenatal combined screening bloods appointment or the antenatal booking appointment, for their CMV serology status on a sample of blood collected as part of the screening process. As part of the ethical approval sought for the RACE-FIT study and the cCHIPS study, the pregnant women screened and found to be CMV seronegative will be eligible for recruitment into the RACE-FIT study and those screened and found to be CMV seropositive will be eligible and approached for recruitment into the cCHIPS study. The cCHIPS study aim to recruit over a 6 month period. The study involves four visits (Visit 1, Visit 2, Visit 3, Visit 4) for each participant. The total study period for each participant will be between 6 to 8 months.

Detailed Description
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The potential participants will be contacted via telephone, email and/or post by the study team. They will be screened for their eligibility, and if they are interested in participating, the first study visit (Visit 1) will be arranged where the written informed consent will be obtained then before any study related procedures. Visit 1 will be held as soon as possible following screening, aiming up to 16 weeks and 6 days gestational age (early in pregnancy). Visit 2 will be aimed to coincide with the routine 20 gestational week appointment or any time in second trimester from 17 weeks and 0 days gestational age to 27 weeks and 6 days gestational age (middle of pregnancy). Visit 3 will be aimed to coincide with the routine 28 gestational week appointment or any time in the third trimester from 28 weeks and 0 days gestational age onwards (late in pregnancy), Visit 4 will be aimed to coincide with the participant's routine admission on the labour ward or postnatal ward after giving birth, or anytime from the time of birth to 1 week postnatal age (postpartum period). At each study visit, the participants will be performing their own study samples of saliva, urine and vaginal secretions using the study specific self-sampling instructions provided. These self-samples will be tested for the presence and quantity of CMV DNA detected via a molecular technique called polymerase chain reaction (PCR). If consent is obtained, a blood sample will also be collected at each study visit to test for cellular mediated immunity. At the last visit, the participant will be offered to have her newborn baby tested for congenital CMV by collecting the newborn's saliva sample which will be tested for CMV DNA via PCR. At each study visit, the participant will complete a short questionnaire on the participant's contact with their child(ren)'s saliva and urine (to identify risk factors for CMV shedding). At Visit 1, the participant will complete a background questionnaire (also to identify risk factors for CMV shedding)and at Visit 4 a feedback questionnaire (to assess feasibility). Where possible the study visits and blood samples will be aimed to take place alongside the participants' routine antenatal appointments and routine blood tests respectively. At the end of the study, up to 20 participants will be invited to take part in a process evaluation in the form of an interview by phone, skype or face to face to explore in depth the experiences of participation in the study.

Official Title
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An Observational, Longitudinal, Natural History, Feasibility Cohort Study to Evaluate the Characteristics of Cytomegalovirus (CMV) Shedding in CMV Seropositive Women Throughout Pregnancy

Conditions
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CMV, Congenital Cmv, Maternal Infections Affecting Fetus or Newborn, Shedding Virus

Intervention / Treatment
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* Other: No intervention- not applicable


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant CMV seropositive Willing and able to provide informed consent Living with child(ren), at least one of whom is less than four years old Willing to have saliva, urine and vaginal secretion sampling to be tested for CMV PCR Willing to be followed up until the postpartum period Exclusion Criteria: Age less than 18 years Evidence of acute maternal CMV infection at the time of screening Documented immunodeficiency of any aetiology including the use of oral steroid therapy equivalent to >1mg/kg of prednisone per day for more than one week In the opinion of the investigator is unlikely to comply with the study procedures In the opinion of the investigator does not have adequate understanding or verbal and written English

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: No intervention- not applicable|No intervention - not applicable|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The prevalence of CMV shedding in saliva, urine and vaginal secretions of CMV seropositive women throughout pregnancy | The percentage of subjects with detectable CMV virus (detected via polymerase chain reaction) in any bodily fluid (saliva, urine or vaginal secretions) at any point in pregnancy | 20 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The quantity of CMV shedding in saliva, urine and vaginal secretions of CMV seropositive women throughout pregnancy | The quantity of detectable CMV virus (measured via quantitative polymerase chain reaction) in saliva, urine and vaginal secretions at individual study visits and cumulatively | 20 months | 
| The fold-differences in the prevalence of CMV shedding in saliva, urine and vaginal secretions in CMV seropositive women throughout pregnancy | The fold-differences in the percentage of subjects with detectable CMV virus (detected via polymerase chain reaction) between saliva, urine and vaginal secretions | 20 months | 
| The fold-differences in the prevalence of CMV shedding in saliva, urine and vaginal secretions between different gestational stages of pregnancy in CMV seropositive women | The fold-differences in the percentage of subjects with detectable CMV virus in saliva, urine and vaginal secretions (detected via polymerase chain reaction) between early in pregnancy, middle of pregnancy, and late in pregnancy, | 20 months | 
| The fold-differences in the quantity of CMV shedding in saliva, urine and vaginal secretions in CMV seropositive women throughout pregnancy | The fold-differences in the quantity of detectable CMV virus (measured via quantitative polymerase chain reaction) between saliva, urine and vaginal secretions | 20 months | 
| The fold-differences in the quantity of CMV shedding in saliva, urine and vaginal secretions between different gestational stages of pregnancy in CMV seropositive women | The fold-differences in the quantity of detectable CMV virus in saliva, urine and vaginal secretions (measured via quantitative polymerase chain reaction) between early in pregnancy, middle of pregnancy and late in pregnancy | 20 months | 
| The association of contact between pregnant women and their young children's urine and saliva with CMV shedding in CMV seropositive pregnant women | The association between CMV shedding and specific types of handling of child(ren)'s urine and saliva by the participants, as a binary outcome (detectable shedding versus no detectable shedding), will be investigated using multivariable mixed effects models, assessed using the contact questionnaire at all study visits (Visit 1, Visit 2, Visit 3 and Visit 4) | 20 months | 
| The acceptability of the study procedures to participating pregnant women | Acceptability of the study procedures to participants will be analysed descriptively. Any free text comments made through the feedback questionnaire completed by participants at the last visit will be summarised. | 20 months | 
| The proportion of women approached who are recruited into the study | The percentage of women approached who are recruited into the study | 20 months | 
| The proportion of participants completing the study | The percentage of participants who complete the study (provide urine, saliva and vaginal secretion samples and questionnaire data at all four study visits, with or without blood and newborn saliva samples) | 20 months | 
| The association between CMV-specific T cell immune response and CMV shedding in CMV seropositive pregnant women as measured by CMV-QuantiFERON | The percentage of reactive IFN-γ in the plasma as measured by CMV-QuantiFERON assay when CMV shedding in saliva, urine or vaginal secretions occurs in the participant | 20 months | 
| The association between CMV-specific T cell immune response and CMV shedding in CMV seropositive pregnant women as measured by CMV-ELISPOT | The percentage of reactive IFN-γ in the plasma as measured by CMV-ELISPOT assay when CMV shedding in saliva, urine or vaginal secretions occurs in the participant | 20 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cmv, cytomegalovirus, shedding, excretion, congenital, cCMV, seropositive, maternal