Cytomegalovirus CongenitalNCT03722615
Epidemiology of Congenital Cytomegalovirus in a High HIV Prevalence Setting, South Africa
An observational study of Cytomegalovirus Congenital and Hearing Loss, run by University of Witwatersrand, South Africa at 1 site in South Africa.
Trial summary
The aim of this project is to determine the epidemiology of congenital cytomegalovirus (CMV) infection and incidence of subsequent permanent neurological sequelae in a high HIV prevalent setting in Soweto, Johannesburg. Read more about this study
- Who is it for?
- Ages 1 minute to 48 hoursHealthy volunteers can take part
- Conditions the study is for
- Cytomegalovirus Congenital, Hearing Loss, Neurodevelopmental Disorders
- How many people
- 3,000 participants
- Where
- 1 siteSouth Africa
- Study dates
- 6 May 2016to 1 Apr 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 minute to 48 hours
- All sexes
- Healthy volunteers accepted
- Child
Study population: Newborns of women aged 18 years or older born at Chris Hani Baragwanath Academic hospital in the Johannesburg area enrolled in V98_28OBTP (NCT02215226). Stillbirths and Neonatal deaths at Chris Hani Baragwanath Academic hospital in the Johannesburg area.
Who may be able to join
- Mother's age ≥18y
- Residing in Soweto and would be available for study follow-up
- Consents to enrol self and baby in study
Who cannot join
- Mother not enrolled in V98_28OBTP (NCT02215226)
Trial locations and contacts
1 site in 1 country.
South Africa1 site
Respiratory and Meningeal Pathogen Research Unit, Soweto
Johannesburg
About this study
The aim of this project is to determine the epidemiology of congenital cytomegalovirus (CMV) infection and incidence of subsequent permanent neurological sequelae in a high HIV prevalent setting in Soweto, Johannesburg. A cross-sectional study will be conducted on mother-infant pairs, screening mothers for CMV infection and newborns for congenital CMV infection. Maternal CMV prevalence will be determined by testing for CMV specific antibodies in blood. Newborn congenital infection will be determined by polymerase chain reaction (PCR) tests on newborn saliva and urine within 3 weeks of birth. Various risk factors associated with congenital CMV such as HIV exposure, and gestational age will be assessed. The association between maternal vaginal CMV shedding postnatally with congenital CMV infection will be explored by swabbing maternal vaginal fluid and conducting quantitative CMV PCR analysis. Newborns confirmed with congenital CMV and a control group of uninfected newborns will form a cohort to be followed up until 12 months of age monitoring for various neurological sequelae such as hearing loss, neurodevelopmental impairment, ocular damage, cerebral damage and seizures.
A comparison of vaccine immune responses between cases of congenital CMV and the CMV uninfected infants to the primary series of vaccines in the National Expanded Programme on Immunisation will be compared. The contribution of CMV infection to neonatal death and stillbirths will be described by minimally invasive tissue sampling (MITS) for CMV on babies that die during the neonatal period and stillbirths.
- Conditions
- Cytomegalovirus Congenital, Hearing Loss, Neurodevelopmental Disorders, Immunogenicity, Neonatal Death, Stillbirth
- Medical subject headings
- Cytomegalovirus Infections, Hearing Loss, Neurodevelopmental Disorders, Perinatal Death, Stillbirth
What is being measured
The primary outcome is the main question the study is designed to answer.
Prevalence of congenital cytomegalovirus infection in HIV exposed and HIV unexposed newborns
Prevalence will be determined by testing a saliva sample collected at birth for CMV DNA by polymerase chain reaction (PCR) assay. Newborns that test positive for CMV at birth will have confirmatory testing done within 3 weeks of birth by testing a repeat saliva and urine sample for CMV DNA by PCR. Confirmed cases will be divided by the total number of newborns screened, stratified by HIV exposure status to determine CMV prevalence.
Measured: May 2016 - December 2016
Incidence of sensorineural hearing loss in congenital CMV infected and uninfected infants, assessed by visual reinforced audiometry
Screening for sensorineural hearing loss is initially conducted by acoustic reflex testing (ART) and distortion product otoacoustic emissions (DPOAE). To pass ART testing, the infant will have to obtain at least two reflexes at either 0.5, 1, 2 and/or 4kHz in both ears. To pass DPOAE testing, the infant will have to pass at least 3 frequencies (2,3,4 and/or 5kHz) in both ears, which is an overall pass. If any of ART or DPOAE has not been passed, the child will have diagnostic visual reinforced audiometry. Hearing thresholds will be defined as: 0 to 20 dB for normal hearing, 21 to 45 dB for mild hearing loss, 46 to 70 dB for moderate hearing loss, and 71 dB or higher for severe hearing loss.
Measured: May 2016 - May 2019
Incidence of neurodevelopmental delay in congenital CMV infected and uninfected children at one year of age assessed by scores obtained in the Bayley III developmental assessment tool.
The Bayley III scales of infant and toddler development assess the neurodevelopmental domains based on observed responses to a set of tasks presented to the child which are scored directly on the following subscales: cognitive scale, language summed scale of receptive and expressive language subscales and motor summed scale of fine and gross-motor subscales. Composite scores are derived from raw scores for cognitive, language, and motor development and scaled to a metric, with a mean of 100, standard deviation of 15, and range of 40 to 160. Performance that is 2.0 or more standard deviations below the mean score for each group will be used to define neurodevelopmental delay at 6 and 12 months.
Measured: May 2017 to March 2018
Secondary outcomes (2)
Prevalence of CMV infection in stillbirths and neonatal deaths
Prevalence of in-utero CMV infection in stillbirths and neonatal deaths (occurring before 3 weeks age) and sites of infection. Minimally invasive tissue sampling of the major organs (lungs, brain, liver) and cerebrospinal fluid and blood samples will be tested for CMV by PCR assay.
Measured: July 2015 to August 2016
Immunogenicity to primary series of childhood vaccinations in congenital CMV infected and uninfected children
When infants are aged 6 months a venous blood sample will be collected. Antibody to diphtheria toxoid, tetanus-toxoid, pertussis toxoid, filamentous hemagglutinin (FHA) and hepatitis B surface antigen (HBsAg) will be measured by an in-house Luminex multiplex immunoassay. Immune responses to the primary series of PCV will be measured by a standardized enzyme immunoassay (EIA) to test for vaccine serotype-specific capsular immunoglobulin (Ig) G antibody concentrations and opsonophagocytic assay.
Measured: October 2016 to February 2018
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2018
- Study start6 May 2016
- Primary completion1 Apr 2019
- Study completion1 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cytomegalovirus CongenitalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 3,000 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Witwatersrand, South Africa
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jayani Pathirana, University of Witwatersrand, South Africa
- Investigators
- Shabir A Madhi, Study director, Univeristy of Witwatersrand, South Africa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03722615
- Sponsor's protocol ID
- M151161
- Status last verified
- Aug 2019
- First submitted
- 19 Oct 2018
- Last updated
- 6 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Epidemiology of Congenital Cytomegalovirus in a High HIV Prevalence Setting, South Africa
- ClinicalTrials.gov ID
- NCT03722615
- Acronym / sponsor ID
- M151161
- Conditions
- Cytomegalovirus Congenital, Hearing Loss, Neurodevelopmental Disorders, Immunogenicity, Neonatal Death, Stillbirth
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 3,000 participants (actual)
- Lead sponsor
- University of Witwatersrand, South AfricaUniversity, hospital or other
- Study start
- 6 May 2016 (actual)
- Primary completion
- 1 Apr 2019 (actual)
- Study completion
- 1 Apr 2019 (actual)
- First posted
- 29 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this project is to determine the epidemiology of congenital cytomegalovirus (CMV) infection and incidence of subsequent permanent neurological sequelae in a high HIV prevalent setting in Soweto, Johannesburg. A cross-sectional study will be conducted on mother-infant pairs, screening mothers for CMV infection and newborns for congenital CMV infection. Maternal CMV prevalence will be determined by testing for CMV specific antibodies in blood. Newborn congenital infection will be determined by polymerase chain reaction (PCR) tests on newborn saliva and urine within 3 weeks of birth. Various risk factors associated with congenital CMV such as HIV exposure, and gestational age will be assessed. The association between maternal vaginal CMV shedding postnatally with congenital CMV infection will be explored by swabbing maternal vaginal fluid and conducting quantitative CMV PCR analysis. Newborns confirmed with congenital CMV and a control group of uninfected newborns will form a cohort to be followed up until 12 months of age monitoring for various neurological sequelae such as hearing loss, neurodevelopmental impairment, ocular damage, cerebral damage and seizures.
A comparison of vaccine immune responses between cases of congenital CMV and the CMV uninfected infants to the primary series of vaccines in the National Expanded Programme on Immunisation will be compared. The contribution of CMV infection to neonatal death and stillbirths will be described by minimally invasive tissue sampling (MITS) for CMV on babies that die during the neonatal period and stillbirths.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 1 minute to 48 hours
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- Newborns of women aged 18 years or older born at Chris Hani Baragwanath Academic hospital in the Johannesburg area enrolled in V98_28OBTP (NCT02215226). Stillbirths and Neonatal deaths at Chris Hani Baragwanath Academic hospital in the Johannesburg area.
Key inclusion criteria (3 listed)
- Mother's age ≥18y
- Residing in Soweto and would be available for study follow-up
- Consents to enrol self and baby in study
Key exclusion criteria (1 listed)
- Mother not enrolled in V98_28OBTP (NCT02215226)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Prevalence of congenital cytomegalovirus infection in HIV exposed and HIV unexposed newborns
Time frame: May 2016 - December 2016
Prevalence will be determined by testing a saliva sample collected at birth for CMV DNA by polymerase chain reaction (PCR) assay. Newborns that test positive for CMV at birth will have confirmatory testing done within 3 weeks of birth by testing a repeat saliva and urine sample for CMV DNA by PCR. Confirmed cases will be divided by the total number of newborns screened, stratified by HIV exposure status to determine CMV prevalence.
Incidence of sensorineural hearing loss in congenital CMV infected and uninfected infants, assessed by visual reinforced audiometry
Time frame: May 2016 - May 2019
Screening for sensorineural hearing loss is initially conducted by acoustic reflex testing (ART) and distortion product otoacoustic emissions (DPOAE). To pass ART testing, the infant will have to obtain at least two reflexes at either 0.5, 1, 2 and/or 4kHz in both ears. To pass DPOAE testing, the infant will have to pass at least 3 frequencies (2,3,4 and/or 5kHz) in both ears, which is an overall pass. If any of ART or DPOAE has not been passed, the child will have diagnostic visual reinforced audiometry. Hearing thresholds will be defined as: 0 to 20 dB for normal hearing, 21 to 45 dB for mild hearing loss, 46 to 70 dB for moderate hearing loss, and 71 dB or higher for severe hearing loss.
Incidence of neurodevelopmental delay in congenital CMV infected and uninfected children at one year of age assessed by scores obtained in the Bayley III developmental assessment tool.
Time frame: May 2017 to March 2018
The Bayley III scales of infant and toddler development assess the neurodevelopmental domains based on observed responses to a set of tasks presented to the child which are scored directly on the following subscales: cognitive scale, language summed scale of receptive and expressive language subscales and motor summed scale of fine and gross-motor subscales. Composite scores are derived from raw scores for cognitive, language, and motor development and scaled to a metric, with a mean of 100, standard deviation of 15, and range of 40 to 160. Performance that is 2.0 or more standard deviations below the mean score for each group will be used to define neurodevelopmental delay at 6 and 12 months.
2 secondary outcomes
Prevalence of CMV infection in stillbirths and neonatal deaths
Time frame: July 2015 to August 2016
Immunogenicity to primary series of childhood vaccinations in congenital CMV infected and uninfected children
Time frame: October 2016 to February 2018
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shabir A Madhi study director
Univeristy of Witwatersrand, South Africa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cytomegalovirus Congenital and Hearing Loss, run by University of Witwatersrand, South Africa at 1 site in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prevalence of congenital cytomegalovirus infection in HIV exposed and HIV unexposed newborns (time frame: May 2016 - December 2016). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2019.