Congenital Heart DiseaseCHARMEDNCT04769167
Congenital Heart Anomaly Risk in Maternal Enteroviral Infection and Diabetes
A study testing Stool and Blood Specimen Collection and Follow-up Medical Record Review in people with Congenital Heart Disease and Viremia, run by Washington University School of Medicine at 2 sites in United States.
Trial summary
Beyond EV-B, there are clinical observations to implicate other viruses in birth defects, including CHD. Since the Rubella epidemic of 1960s', however, viruses have received little attention and certainly no comprehensive study, especially using next generation sequencing (NGS), has been undertaken in this context. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Congenital Heart Disease, Viremia, Virus Diseases
- What is being tested?
- Stool and Blood Specimen Collection and Follow-up Medical Record Review
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 114 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Feb 2021to 5 Dec 2023
- Phase
- Interventional
- 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 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
None listed.
Who cannot join
- Women under the age of 18 or older than 45.
- Prediabetes defined as an HbA1C between 5.7% and 6.5% or current diagnosis of pancreatic diabetes or gestational diabetes (GDM).
- Body Mass Index greater than or equal to 35 or less than or equal to 18.
- Women unable to give informed consent and/or considered a prisoner.
- Use of any of the following drugs within the last 6 months:
- 5a.Systemic antibiotics, antifungals, antivirals or antiparasitics (intravenous, intramuscular, or oral); 5b.Cytokines; 5c. Immunomodulators or immunosuppressive cytotoxic agents; 5d. Large doses of commercial probiotics consumed (greater than or equal to 108 cfu or organisms per day) - includes tablets, capsules, lozenges, chewing gum or powders in which probiotic is a primary component. Ordinary dietary components such as fermented beverages/milks, yogurts, foods do not apply.
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- 6. A positive test for HIV, HBV or HCV or any confirmed or suspected condition/state of immunosuppression or immunodeficiency.
- 7. History of autoimmune disorders other than T1D or treated thyroid disease.
- 8. Major surgery of the GI tract, except for cholecystectomy and appendectomy, in the past five years.
- 9. Any major bowel resection at any time.
- 10. History of active uncontrolled gastrointestinal disorders or diseases including: 10a. Inflammatory bowel disease (IBD) including ulcerative colitis (mild-moderate-severe), 10b. Crohn's disease (mild-moderate-severe), or indeterminate colitis; 10c. Irritable bowel syndrome (IBS) (moderate-severe); 10d. Persistent, infectious gastroenteritis, colitis or gastritis, persistent or chronic diarrhea of unknown etiology, Clostridium difficile infection (recurrent) or Helicobacter pylori infection (untreated).
- 11. Acute disease at the time of enrollment (defer sampling until subject recovers). Acute disease is defined as the presence of a moderate or severe illness with or without fever.
- 12. Use of assisted reproductive technology (ART)including but not limited to In vitro Fertilization (IVF), Gamete intrafallopian transfer (GIFT) and Zygote intrafallopian transfer (ZIFT).
- 13. Any other condition which, in the opinion of the investigators, renders the patient unfit for study participation and procedures.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Barnes Jewish Hospital
St Louis, Missouri, 63110
St Louis Childrens Hospital
St Louis, Missouri, 63110
About this study
Beyond EV-B, there are clinical observations to implicate other viruses in birth defects, including CHD. Since the Rubella epidemic of 1960s', however, viruses have received little attention and certainly no comprehensive study, especially using next generation sequencing (NGS), has been undertaken in this context. The current pandemic as well as those caused by Zika, influenza, Ebola and Lassa Fever (among many) have shown pregnant women and their baby are at high risk. Therefore, an open-minded approach is warranted when considering the role of maternal viral infections in CHD. Even less is known about maternal immune response, such as antibody production, to these viruses.
The investigator's goal is to answer the above gaps in knowledge. The investigators propose to do that using two different approaches; one retrospective (analysis of samples in two existing, large biorepositories) and the other prospective. The investigator's have created a multi-disciplinary team to bring together the needed expertise from individuals who have overlapping and vested interest in this project.
The investigator's specific aim is to examine the diversity of the gut virome in non-pregnant and pregnant women with and without diabetes, with special emphasis on known cardiotropic viruses (those with tropism for cardiac tissues). This study is seen by the investigator's as the first step prior to a larger prospective multi-institutional study to specifically assess the linkage between the maternal virome and CHD pathogenesis.
Read the detailed description
To determine prevalence in non-pregnant women (i) the investigators will perform PCR analysis of stool and blood from a prospective cohort of 225 women with diabetes (and 225 without) and sequence the amplicons, and (ii) perform ELISA (IgM and IgG) analysis of sera collected concurrently. They will assay IgM/IgG positive samples for neutralizing antibodies. To determine prevalence in pregnant women (i) the investigators will perform PCR analysis of 1st trimester stool and blood from a prospective cohort of 450 women with diabetes (and 450 without diabetes) and sequence the amplicons, and (ii) perform ELISA (IgM and IgG) analysis of sera collected at 1st and 2nd or 3rd trimester. They will assay IgM/IgG positive samples for neutralizing antibodies.
The investigators will also perform a comprehensive virome analysis using metagenomic shotgun sequencing with ViroCap enrichment, a method developed by co-PI, on 1st trimester stool samples from a subset (~4-500) of women (both EVB positive and negative) enrolled in Aim 1. The investigators will complement this data with VirScan® analysis of blood collected from the same women at 1st and 2nd/3rd trimester. VirScan® is a revolutionary new technique for comprehensive profiling of sera for antibodies against ~400 species and strains of pathogenic viruses.
- Conditions
- Congenital Heart Disease, Viremia, Virus Diseases, Enterovirus, Enterovirus Infections, Heart Defects, Congenital
- Being tested
- Stool and Blood Specimen Collection, Follow-up Medical Record Review
- Medical subject headings
- Heart Defects, Congenital, Viremia, Virus Diseases, Enterovirus Infections, Heart Diseases, Diabetes Mellitus, Diabetes Mellitus, Type 2, Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stool and Blood Specimen CollectionOther
Stool and Blood specimens will be collected at 3 designated time points
Follow-up Medical Record ReviewOther
Participant medical records as well as the medical records of infants during study enrollment will be reviewed up to 3 years from the date of enrollment.
| Study group | Role | What they receive |
|---|---|---|
| Healthy Non Pregnant Women (HNPW) | Placebo comparator | HNPW are healthy women and not pregnant Receives: Other: Stool and Blood Specimen Collection; Other: Follow-up Medical Record Review |
| Diabetic Non Pregnant Women (DNPW) | Active comparator | DNPW are diabetic and not pregnant Receives: Other: Stool and Blood Specimen Collection; Other: Follow-up Medical Record Review |
| Healthy Pregnant Women (HPW) | Placebo comparator | HNPW are healthy women and currently pregnant Receives: Other: Stool and Blood Specimen Collection; Other: Follow-up Medical Record Review |
| Diabetic Pregnant Women (DPW) | Active comparator | DNPW are diabetic and currently pregnant Receives: Other: Stool and Blood Specimen Collection; Other: Follow-up Medical Record Review |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prevalence of EVB Viremia
Determine the prevalence of EVB among women with or without diabetes. For this aim, the investigators will use PCR analysis of stool and blood to detect EVB and ELISA (IgM and IgG) of blood to detect anti-EVB antibodies in samples collected from pregnant and non-pregnant women (with or without diabetes) at multiple time points. The investigators will also sequence the PCR amplicons and carry out antibody neutralization assays of IgM/IgG positive samples to identify the specific EVB. The non-pregnant cohort will consist of 225 women with diabetes (and 225 without) sampled at 3-month intervals over 1 years. The pregnant cohort will consist of 450 women with diabetes (and 450 without) with sampling at 1st, 2nd and 3rd trimesters.
Measured: 6 years
Cardiotropic Virus Detection
Determine the burden of other pathogenic human viruses in pregnant women with diabetes. Beyond EVB, other viruses could (and likely do) cause CHD. Further, while PCR is quite sensitive for detection of nucleic acid sequences of interest, its results are primer dependent. Therefore, in this aim, the investigators will perform a comprehensive virome analysis (the viral component of the microbiome) using metagenomic shotgun sequencing with ViroCap enrichment, a method developed by a co-PI of this proposal, on 1st trimester stool samples from a subset (~4-500) of women (both EVB positive and negative) enrolled in Aim 1. The investigators will complement this data with VirScan® (version 3) analysis of blood collected from the same women at 1st and 2nd/3rd trimester. VirScan® is a revolutionary new technique for comprehensive profiling of sera for antibodies against ~400 species and strains of pathogenic human viruses.
Measured: 6 years
Maternal Immune Response
Determine the extent of correlation between EVB and other viruses with CHD. Because CHD cannot typically be diagnosed until 20-24 weeks gestation and the investigators are prospectively enrolling participants at 6-14 weeks, they will not know which participants will develop CHD during the enrolled pregnancies. The investigators anticipate ~40-50 CHD-affected pregnancies. If not done in Aim 2, the investigators will carry out virome (blood and stool) and VirScan® (blood) analysis of 1st trimester samples from these women.
Measured: 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2021
- Study start1 Feb 2021
- Primary completion5 Dec 2023
- Study completion5 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Congenital Heart DiseaseStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Screening
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Model description
- All participants will provide the same biologic specimens (stool \& blood) during their study arm's designated timeframe. All collected specimens will be analyzed per the study protocol.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 114 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pirooz Eghtesady, MD, PhD, Principal investigator, Faculty
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04769167
- Sponsor's protocol ID
- 202002043
- Acronym
- CHARMED
- Status last verified
- Dec 2025
- First submitted
- 14 Feb 2021
- Last updated
- 24 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: The IPD collected in this study will be house in the PI's Biospecimen and Data Repository. Plans to make IPD available to other researchers has not been determined.
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Congenital Heart Anomaly Risk in Maternal Enteroviral Infection and Diabetes
- ClinicalTrials.gov ID
- NCT04769167
- Acronym / sponsor ID
- CHARMED / 202002043
- Conditions
- Congenital Heart Disease, Viremia, Virus Diseases, Enterovirus, Enterovirus Infections, Heart Defects, Congenital
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 114 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 1 Feb 2021 (actual)
- Primary completion
- 5 Dec 2023 (actual)
- Study completion
- 5 Dec 2023 (actual)
- First posted
- 24 Feb 2021 (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.
Beyond EV-B, there are clinical observations to implicate other viruses in birth defects, including CHD. Since the Rubella epidemic of 1960s', however, viruses have received little attention and certainly no comprehensive study, especially using next generation sequencing (NGS), has been undertaken in this context. The current pandemic as well as those caused by Zika, influenza, Ebola and Lassa Fever (among many) have shown pregnant women and their baby are at high risk. Therefore, an open-minded approach is warranted when considering the role of maternal viral infections in CHD. Even less is known about maternal immune response, such as antibody production, to these viruses.
The investigator's goal is to answer the above gaps in knowledge. The investigators propose to do that using two different approaches; one retrospective (analysis of samples in two existing, large biorepositories) and the other prospective. The investigator's have created a multi-disciplinary team to bring together the needed expertise from individuals who have overlapping and vested interest in this project.
The investigator's specific aim is to examine the diversity of the gut virome in non-pregnant and pregnant women with and without diabetes, with special emphasis on known cardiotropic viruses (those with tropism for cardiac tissues). This study is seen by the investigator's as the first step prior to a larger prospective multi-institutional study to specifically assess the linkage between the maternal virome and CHD pathogenesis.
Detailed description
To determine prevalence in non-pregnant women (i) the investigators will perform PCR analysis of stool and blood from a prospective cohort of 225 women with diabetes (and 225 without) and sequence the amplicons, and (ii) perform ELISA (IgM and IgG) analysis of sera collected concurrently. They will assay IgM/IgG positive samples for neutralizing antibodies. To determine prevalence in pregnant women (i) the investigators will perform PCR analysis of 1st trimester stool and blood from a prospective cohort of 450 women with diabetes (and 450 without diabetes) and sequence the amplicons, and (ii) perform ELISA (IgM and IgG) analysis of sera collected at 1st and 2nd or 3rd trimester. They will assay IgM/IgG positive samples for neutralizing antibodies.
The investigators will also perform a comprehensive virome analysis using metagenomic shotgun sequencing with ViroCap enrichment, a method developed by co-PI, on 1st trimester stool samples from a subset (~4-500) of women (both EVB positive and negative) enrolled in Aim 1. The investigators will complement this data with VirScan® analysis of blood collected from the same women at 1st and 2nd/3rd trimester. VirScan® is a revolutionary new technique for comprehensive profiling of sera for antibodies against ~400 species and strains of pathogenic viruses.
Study design
- Primary purpose
- Screening
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- Single blind (participant)
- Number of arms
- 4
- Model description
- All participants will provide the same biologic specimens (stool \& blood) during their study arm's designated timeframe. All collected specimens will be analyzed per the study protocol.
| Arm | Type | Receives |
|---|---|---|
| Healthy Non Pregnant Women (HNPW) | Placebo comparator | Other: Stool and Blood Specimen Collection, Other: Follow-up Medical Record ReviewHNPW are healthy women and not pregnant |
| Diabetic Non Pregnant Women (DNPW) | Active comparator | Other: Stool and Blood Specimen Collection, Other: Follow-up Medical Record ReviewDNPW are diabetic and not pregnant |
| Healthy Pregnant Women (HPW) | Placebo comparator | Other: Stool and Blood Specimen Collection, Other: Follow-up Medical Record ReviewHNPW are healthy women and currently pregnant |
| Diabetic Pregnant Women (DPW) | Active comparator | Other: Stool and Blood Specimen Collection, Other: Follow-up Medical Record ReviewDNPW are diabetic and currently pregnant |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (0 listed)
Key exclusion criteria (14 listed)
- Women under the age of 18 or older than 45.
- Prediabetes defined as an HbA1C between 5.7% and 6.5% or current diagnosis of pancreatic diabetes or gestational diabetes (GDM).
- Body Mass Index greater than or equal to 35 or less than or equal to 18.
- Women unable to give informed consent and/or considered a prisoner.
- Use of any of the following drugs within the last 6 months:
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 |
|---|---|---|
| Stool and Blood Specimen CollectionStool and Blood specimens will be collected at 3 designated time points | Other | Diabetic Non Pregnant Women (DNPW), Diabetic Pregnant Women (DPW), Healthy Non Pregnant Women (HNPW), Healthy Pregnant Women (HPW) |
| Follow-up Medical Record ReviewParticipant medical records as well as the medical records of infants during study enrollment will be reviewed up to 3 years from the date of enrollment. | Other | Diabetic Non Pregnant Women (DNPW), Diabetic Pregnant Women (DPW), Healthy Non Pregnant Women (HNPW), Healthy Pregnant Women (HPW) |
Primary outcome
Prevalence of EVB Viremia
Time frame: 6 years
Determine the prevalence of EVB among women with or without diabetes. For this aim, the investigators will use PCR analysis of stool and blood to detect EVB and ELISA (IgM and IgG) of blood to detect anti-EVB antibodies in samples collected from pregnant and non-pregnant women (with or without diabetes) at multiple time points. The investigators will also sequence the PCR amplicons and carry out antibody neutralization assays of IgM/IgG positive samples to identify the specific EVB. The non-pregnant cohort will consist of 225 women with diabetes (and 225 without) sampled at 3-month intervals over 1 years. The pregnant cohort will consist of 450 women with diabetes (and 450 without) with sampling at 1st, 2nd and 3rd trimesters.
Cardiotropic Virus Detection
Time frame: 6 years
Determine the burden of other pathogenic human viruses in pregnant women with diabetes. Beyond EVB, other viruses could (and likely do) cause CHD. Further, while PCR is quite sensitive for detection of nucleic acid sequences of interest, its results are primer dependent. Therefore, in this aim, the investigators will perform a comprehensive virome analysis (the viral component of the microbiome) using metagenomic shotgun sequencing with ViroCap enrichment, a method developed by a co-PI of this proposal, on 1st trimester stool samples from a subset (~4-500) of women (both EVB positive and negative) enrolled in Aim 1. The investigators will complement this data with VirScan® (version 3) analysis of blood collected from the same women at 1st and 2nd/3rd trimester. VirScan® is a revolutionary new technique for comprehensive profiling of sera for antibodies against ~400 species and strains of pathogenic human viruses.
Maternal Immune Response
Time frame: 6 years
Determine the extent of correlation between EVB and other viruses with CHD. Because CHD cannot typically be diagnosed until 20-24 weeks gestation and the investigators are prospectively enrolling participants at 6-14 weeks, they will not know which participants will develop CHD during the enrolled pregnancies. The investigators anticipate ~40-50 CHD-affected pregnancies. If not done in Aim 2, the investigators will carry out virome (blood and stool) and VirScan® (blood) analysis of 1st trimester samples from these women.
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 24 Dec 2025.
- Individual participant dataSharing planned: Undecided. The IPD collected in this study will be house in the PI's Biospecimen and Data Repository. Plans to make IPD available to other researchers has not been determined.
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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.
Pirooz Eghtesady, MD, PhD principal investigator
Faculty
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Stool and Blood Specimen Collection and Follow-up Medical Record Review in people with Congenital Heart Disease and Viremia, run by Washington University School of Medicine at 2 sites in United States.
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 0 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: finished, as of the sponsor's last update on 24 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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. Some participants in this study may receive a placebo. 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 EVB Viremia (time frame: 6 years). 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 24 Dec 2025.