Cytomegalovirus Shedding Characteristics in Pregnant Women

CMV Clinical Trial

— cCHIPS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04021628
• Other study ID #: 2018.0296
• Status: Completed
• Start date: April 1, 2019
• Est. completion date: December 1, 2021

Study information

• Verified date: December 2023
• Source: St George's, University of London
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: December 1, 2021
• Est. primary completion date: October 1, 2021
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• CMV
• Congenital Cmv
• Maternal Infections Affecting Fetus or Newborn
• Shedding Virus

Intervention

Other:
• No intervention- not applicable
No intervention - not applicable

Locations

Country	Name	City	State
United Kingdom	St George's University Hospitals NHS Foundation Trust	London

Sponsors (2)

Lead Sponsor	Collaborator
St George's, University of London	St George's University Hospitals NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Prevalence of CMV Shedding in Saliva, Urine and Vaginal Secretions of CMV Seropositive Women in Pregnancy	The percentage of participants with detectable CMV virus (detected via polymerase chain reaction) in any bodily fluid (saliva, urine or vaginal secretions) at any point in pregnancy, and the percentage of participants with detectable CMV virus in each bodily fluid (saliva, urine and vaginal secretions) at any point in pregnancy.	8 months
Secondary	The Proportion of CMV Shedding in Saliva, Urine and Vaginal Secretions of CMV Seropositive Women Throughout Pregnancy and Postpartum	The proportion of detectable CMV virus (measured via polymerase chain reaction) in saliva, urine and vaginal secretions at individual study visits	8 months
Secondary	The Quantity of CMV Shedding in Saliva, Urine and Vaginal Secretions in CMV Seropositive Women Throughout Pregnancy and Postpartum	The quantity of detectable CMV virus (measured via quantitative polymerase chain reaction in IU/ml) in saliva, urine and vaginal secretions at individual study visits	8 months
Secondary	The Proportion of Pregnant Women Approached Who Are Recruited Into the Study	The percentage of women approached who are then recruited into the study	8 months
Secondary	The Proportion of Participating Pregnant Women Completing the Study		8 months
Secondary	The Acceptability of the Study Procedures to Participating Pregnant Women	Descriptive summary of the mean scores of each feedback statement (scale 1 to 5, where higher score was indicative of higher agreement to the feedback statement) from the Feedback Questionnaire completed by participants at the last study visit	8 months
Secondary	The Association of Demographics With CMV Shedding in CMV Seropositive Women in Pregnancy	The multiple logistic regression of CMV shedding as an outcome (dependent variable; detected or not detected) at any visit during pregnancy with demographic factors (independent variable) as a predictor, adjusted for all demographic variables described, using odds ratio in the results between CMV seropositive women with CMV shedding and without CMV shedding, with 95% confidence interval.	8 months
Secondary	The Association of Contact With Young Children's Bodily Fluids With CMV Shedding in CMV Seropositive Women Throughout Pregnancy and Postpartum	The association between CMV shedding detection and the specific types of contact with child(ren)'s bodily fluids as assessed in the contact questionnaire at each visit, performed using logistic regression (CMV shedding detection as the outcome variable, the specific types of contact with children's bodily fluids as the predictor varible), adjusted for age, ethnicity, education, and amount of children, with the detection of shedding as a binary outcome, using odds ratio in the results between CMV-seropositive with CMV shedding and without CMV shedding, with 95% confidence intervals.	8 months
Secondary	The Prevalence of CMV-specific T-cell Immune Responses as Measured by CMV-QuantiFERON in CMV Seropositive Women in Pregnancy	The percentage of the number of participants with positive CMV-QuantiFERON results over the total number of participants tested with CMV-QuantiFERON at any point in pregnancy	8 months
Secondary	The Prevalence of CMV-specific T-cell Immune Responses as Measured by CMV-ELISPOT in CMV Seropositive Women in Pregnancy	The percentage of the number of participants with responsive CMV-ELISPOT results over the total number of participants tested with CMV-ELISPOT at any point in pregnancy	8 months
Secondary	The Proportion of CMV-specific T-cell Immune Responses as Measured by CMV-QuantiFERON in CMV Seropositive Women Throughout Pregnancy and Postpartum	The percentage of the number of participants with positive CMV-QuantiFERON results over the total number of participants tested for CMV-QuantiFERON at each study visit	8 months
Secondary	The Proportion of CMV-specific T-cell Immune Responses as Measured by CMV-ELISPOT in CMV Seropositive Women Throughout Pregnancy and Postpartum	The percentage of the number of participants with responsive CMV-ELISPOT results (a positive spot count to IE-1 and/or pp65 antigen) over the total number of participants tested for CMV-ELISPOT at each study visit	8 months
Secondary	The Association Between CMV-specific T Cell Immune Response and CMV Shedding in CMV Seropositive Pregnant Women as Measured by CMV-QuantiFERON	The logistic regression of CMV shedding as an outcome (dependent variable; detected or not detected) at a visit with CMV-QuantiFERON assay results (independent variable; positive or negative) as a predictor at the reciprocal visit, adjusted for age and ethnicity, using odds ratio in the results between CMV seropositive women with CMV shedding and without CMV shedding, with 95% confidence interval.	8 months
Secondary	The Association Between CMV-specific T Cell Immune Response and CMV Shedding in CMV Seropositive Pregnant Women as Measured by CMV-ELISPOT	The logistic regression of CMV shedding as an outcome (dependent variable; detected or not detected) at a visit with CMV-ELISPOT assay results (independent variable; spot count) as a predictor at the reciprocal visit, adjusted for age and ethnicity, using odds ratio in the results between CMV seropositive women with CMV shedding and without CMV shedding, with 95% confidence interval.	8 months