Cytomegalovirus CongenitalBIO-CCMVNCT03090841
Biomarkers of Cytomegalovirus Fetal Infection and Disease
An observational study of Cytomegalovirus Congenital, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The purposes of this study are to determine 1) if the diagnosis of CMV fetal infection could be done directly in the maternal blood instead of requesting an amniocentesis and 2) if innovative technologies such as proteomic, transcriptomic, methylomic and lipidomic applied in fetal samples could allow the discovery of… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Cytomegalovirus Congenital
- What is being tested?
- Bio-specimen collected
- How many people
- 265 participants
- Where
- 1 siteFrance
- Study dates
- Dec 2016to Jun 2023
- 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 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: * 320 pregnant women with CMV primary infection or carrying a fetus with compatible ultrasound features to obtained 65 infected fetuses and 15 fetuses diagnosed with severely symptomatic infection * 200 controls pregnant women carrying a fetus with aneuploidy-dysgonosomy
Who may be able to join
- CMV cases:
- Informed consent obtained from the mother;
- Pregnant women either with a history of primary CMV infection in pregnancy or carrying a fetus with ultrasound features compatible with CMV infection and willing to have amniocentesis for fetal diagnosis of CMV infection
- Control cases :
- Pregnant women carrying a fetus with aneuploidy-dysgonosomy
Who cannot join
- CMV cases:
- Fetuses older than the 26 weeks of gestation at the time of diagnosis of HCMV infection or impossibility to collect foetal samples by the end of the 26th week of gestation
- Mother unable to understand the protocol
- Absence of informed consent
- Any clinical rationale not to perform cordocentesis
- Mother <18 years age
Show all 14Show fewer
- Administration of immunoglobulins or anti-viral therapy to the mother before the collection of fetal samples or before the diagnosis of symptomatic fetal infection
- Administration of anti-HCMV drugs to the foetus before the collection of fetal samples or before the diagnosis of symptomatic fetal infection
- Administration of immunosuppressive drugs to the mother during pregnancy
- Maternal auto immune disorders
- Multiple pregnancies.
- Control cases :
- Mother unable to understand the protocol
- Absence of informed consent
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Hôpital Necker Enfants-Malades
Paris, 75015
Marianne LERUEZ, MD, PhD, +33 (0) 1 44 49 49 49 62, marianne.leruez@aphp.fr
About this study
Official title: Biomarkers of Fetal Infection and Disease Following Maternal HCMV Infection
The purposes of this study are to determine 1) if the diagnosis of CMV fetal infection could be done directly in the maternal blood instead of requesting an amniocentesis and 2) if innovative technologies such as proteomic, transcriptomic, methylomic and lipidomic applied in fetal samples could allow the discovery of new biomarkers of fetal infection.
Read the detailed description
Human cytomegalovirus (HCMV) is the most common cause of congenital infection worldwide. The diagnosis of CMV fetal infection relies on the detection of viral DNA in amniotic fluid by polymerase chain reaction after amniocentesis. Non-invasive diagnosis of fetal infection directly in maternal blood is not available. Symptoms develop in about 10% of HCMV-infected fetuses. Despite important advance in medical imaging, establishing the prognosis of an infected fetus remains challenging. Thrombocytopenia, blood HCMV DNA, anti-HCMV immunoglobulin M and β2-microglobulin are recognized biomarkers of symptomatic fetal infections. However, the predictive value of these individual markers is not. Omics technologies could help to establish multimarker signatures of symptomatic infections.
The objective of the study is to:
- validate fetal blood HCMV DNA, anti-HCMV immunoglobulin M , β2-microglobulin and platelet count as biomarkers of fetal disease;
- identify new biomarkers of severe fetal disease using transcriptomic, methylomic and lipidomic analyses of fetal blood and of amniotic fluid.
- validate a non-invasive CMV fetal infection diagnosis tool based on deep-sequencing of targeted CMV genes in maternal blood
- Conditions
- Cytomegalovirus Congenital
- Being tested
- Bio-specimen collected
- Keywords
- Cytomegalovirus Congenital, Non-invasive diagnosis, Omics, Biomarkers
- Medical subject headings
- Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bio-specimen collectedBiological
| Study group | Role | What they receive |
|---|---|---|
| CMV cases | bio-specimen collected for pregnant women with CMV infection Receives: Biological: Bio-specimen collected | |
| Control cases | bio-specimen collected for pregnant women carrying a fetus with aneuploidy-dysgonosomy Receives: Biological: Bio-specimen collected |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Abnormal Laboratory Values in fetal blood
Fetal platelet in mm3/ml, β2 microglobulinein mg/L, proteins concentration in mg/L , Metabolites concentration in mmoles/l , Lipids concentration in mmoles/l , RNA messagers concentration in µg/ml profil
Measured: At 23 weeks gestation +/- 3 weeks
Secondary outcomes (2)
Number of Participants With Abnormal Laboratory Values in amniotic fluid
CMV DNA quantification in UI/mL , protein concentration in mg/L, Metabolites concentration in mmoles/l , Lipids concentration in mmoles/l, RNAm concentration in µg/ml profil ,
Measured: At 23 weeks gestation +/- 3 weeks
Non invasive diagnosis of fetal CMV infection in maternal blood in UI/mL.
CMV fetal DNA measurement in maternal blood
Measured: At 23 weeks gestation +/- 5 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2017
- Study startDec 2016
- Primary completionDec 2022 (estimated)
- Study completionJun 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Cytomegalovirus CongenitalStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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
- 265 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yves VILLE, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03090841
- Sponsor's protocol ID
- 14024
- Acronym
- BIO-CCMV
- Status last verified
- Oct 2022
- First submitted
- 3 Jan 2017
- Last updated
- 7 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Benoist G, Salomon LJ, Jacquemard F, Daffos F, Ville Y. The prognostic value of ultrasound abnormalities and biological parameters in blood of fetuses infected with cytomegalovirus. BJOG. 2008 Jun;115(7):823-9. doi: 10.1111/j.1471-0528.2008.01714.x.
PubMed 18485159Fabbri E, Revello MG, Furione M, Zavattoni M, Lilleri D, Tassis B, Quarenghi A, Rustico M, Nicolini U, Ferrazzi E, Gerna G. Prognostic markers of symptomatic congenital human cytomegalovirus infection in fetal blood. BJOG. 2011 Mar;118(4):448-56. doi: 10.1111/j.1471-0528.2010.02822.x. Epub 2010 Dec 24.
PubMed 21199291Desveaux C, Klein J, Leruez-Ville M, Ramirez-Torres A, Lacroix C, Breuil B, Froment C, Bascands JL, Schanstra JP, Ville Y. Identification of Symptomatic Fetuses Infected with Cytomegalovirus Using Amniotic Fluid Peptide Biomarkers. PLoS Pathog. 2016 Jan 25;12(1):e1005395. doi: 10.1371/journal.ppat.1005395. eCollection 2016 Jan.
PubMed 26808779Bourgon N, Fitzgerald W, Aschard H, Magny JF, Guilleminot T, Stirnemann J, Romero R, Ville Y, Margolis L, Leruez-Ville M. Cytokine Profiling of Amniotic Fluid from Congenital Cytomegalovirus Infection. Viruses. 2022 Sep 28;14(10):2145. doi: 10.3390/v14102145.
PubMed 36298700
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomarkers of Fetal Infection and Disease Following Maternal HCMV Infection
- ClinicalTrials.gov ID
- NCT03090841
- Acronym / sponsor ID
- BIO-CCMV / 14024
- Conditions
- Cytomegalovirus Congenital
- Keywords
- Cytomegalovirus Congenital, Non-invasive diagnosis, Omics, Biomarkers
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 265 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Dec 2016
- Primary completion
- Dec 2022 (estimated)
- Study completion
- Jun 2023 (estimated)
- First posted
- 27 Mar 2017 (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 purposes of this study are to determine 1) if the diagnosis of CMV fetal infection could be done directly in the maternal blood instead of requesting an amniocentesis and 2) if innovative technologies such as proteomic, transcriptomic, methylomic and lipidomic applied in fetal samples could allow the discovery of new biomarkers of fetal infection.
Detailed description
Human cytomegalovirus (HCMV) is the most common cause of congenital infection worldwide. The diagnosis of CMV fetal infection relies on the detection of viral DNA in amniotic fluid by polymerase chain reaction after amniocentesis. Non-invasive diagnosis of fetal infection directly in maternal blood is not available. Symptoms develop in about 10% of HCMV-infected fetuses. Despite important advance in medical imaging, establishing the prognosis of an infected fetus remains challenging. Thrombocytopenia, blood HCMV DNA, anti-HCMV immunoglobulin M and β2-microglobulin are recognized biomarkers of symptomatic fetal infections. However, the predictive value of these individual markers is not. Omics technologies could help to establish multimarker signatures of symptomatic infections.
The objective of the study is to:
- validate fetal blood HCMV DNA, anti-HCMV immunoglobulin M , β2-microglobulin and platelet count as biomarkers of fetal disease;
- identify new biomarkers of severe fetal disease using transcriptomic, methylomic and lipidomic analyses of fetal blood and of amniotic fluid.
- validate a non-invasive CMV fetal infection diagnosis tool based on deep-sequencing of targeted CMV genes in maternal blood
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CMV cases | – | Biological: Bio-specimen collectedbio-specimen collected for pregnant women with CMV infection |
| Control cases | – | Biological: Bio-specimen collectedbio-specimen collected for pregnant women carrying a fetus with aneuploidy-dysgonosomy |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- * 320 pregnant women with CMV primary infection or carrying a fetus with compatible ultrasound features to obtained 65 infected fetuses and 15 fetuses diagnosed with severely symptomatic infection * 200 controls pregnant women carrying a fetus with aneuploidy-dysgonosomy
Key inclusion criteria (5 listed)
- Informed consent obtained from the mother;
- Pregnant women either with a history of primary CMV infection in pregnancy or carrying a fetus with ultrasound features compatible with CMV infection and willing to have amniocentesis for fetal diagnosis of CMV infection
- Pregnant women carrying a fetus with aneuploidy-dysgonosomy
Key exclusion criteria (14 listed)
- Fetuses older than the 26 weeks of gestation at the time of diagnosis of HCMV infection or impossibility to collect foetal samples by the end of the 26th week of gestation
- Mother unable to understand the protocol
- Absence of informed consent
- Any clinical rationale not to perform cordocentesis
- Mother <18 years age
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bio-specimen collected | Biological | CMV cases, Control cases |
Primary outcome
Number of Participants With Abnormal Laboratory Values in fetal blood
Time frame: At 23 weeks gestation +/- 3 weeks
Fetal platelet in mm3/ml, β2 microglobulinein mg/L, proteins concentration in mg/L , Metabolites concentration in mmoles/l , Lipids concentration in mmoles/l , RNA messagers concentration in µg/ml profil
2 secondary outcomes
Number of Participants With Abnormal Laboratory Values in amniotic fluid
Time frame: At 23 weeks gestation +/- 3 weeks
Non invasive diagnosis of fetal CMV infection in maternal blood in UI/mL.
Time frame: At 23 weeks gestation +/- 5 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2022.
- Background: PubMed 18485159Benoist G, Salomon LJ, Jacquemard F, Daffos F, Ville Y. The prognostic value of ultrasound abnormalities and biological parameters in blood of fetuses infected with cytomegalovirus. BJOG. 2008 Jun;115(7):823-9. doi: 10.1111/j.1471-0528.2008.01714.x.
- Background: PubMed 21199291Fabbri E, Revello MG, Furione M, Zavattoni M, Lilleri D, Tassis B, Quarenghi A, Rustico M, Nicolini U, Ferrazzi E, Gerna G. Prognostic markers of symptomatic congenital human cytomegalovirus infection in fetal blood. BJOG. 2011 Mar;118(4):448-56. doi: 10.1111/j.1471-0528.2010.02822.x. Epub 2010 Dec 24.
- Background: PubMed 26808779Desveaux C, Klein J, Leruez-Ville M, Ramirez-Torres A, Lacroix C, Breuil B, Froment C, Bascands JL, Schanstra JP, Ville Y. Identification of Symptomatic Fetuses Infected with Cytomegalovirus Using Amniotic Fluid Peptide Biomarkers. PLoS Pathog. 2016 Jan 25;12(1):e1005395. doi: 10.1371/journal.ppat.1005395. eCollection 2016 Jan.
- Derived from this study: PubMed 36298700Bourgon N, Fitzgerald W, Aschard H, Magny JF, Guilleminot T, Stirnemann J, Romero R, Ville Y, Margolis L, Leruez-Ville M. Cytokine Profiling of Amniotic Fluid from Congenital Cytomegalovirus Infection. Viruses. 2022 Sep 28;14(10):2145. doi: 10.3390/v14102145.
- Individual participant dataSharing planned: No
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Cytomegalovirus Infection
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.
Yves VILLE, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
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, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 5 inclusion and 14 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: status not confirmed, as of the sponsor's last update on 7 Nov 2022. 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 France. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Marianne LERUEZ, MD, PhD (+33 (0) 1 44 49 49 49 62, marianne.leruez@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Abnormal Laboratory Values in fetal blood (time frame: At 23 weeks gestation +/- 3 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03090841, which also lists 4 linked publications.
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 7 Nov 2022.