Cardiovascular PhenotypeNCT05548881
Implications of Maternal 45,X Mosaicism as a Secondary Genomic Finding Following Cell-Free DNA Sequencing During Pregnancy: A Deep Phenotype Study
An observational study of Cardiovascular Phenotype and Metabolic Phenotype, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
Trial summary
Background: Mosaicism is a condition in which cells within the same person have a different genetic makeup. Sometimes, a type of mosaicism called 45,X may not be discovered in a woman until she undergoes routine tests during pregnancy. Little is known about how 45,X mosaicism may affect a person s long-term health. Read more about this study
- Who is it for?
- Ages 18 to 99 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Phenotype, Metabolic Phenotype, Hypertensive Disease
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2025to 1 Apr 2025
- 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 to 99 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Study population: Women who have submitted clinical samples for prenatal aneuploidy screening test with the finding of X mosaicism will be recruited from laboratories that offer cell-free DNA testing during pregnancy as well as nation-wide obstetricians and maternal-fetal-medicine specialists Potential participants are likely to be referred from specialists who care for them or will find the protocol through an internet search A control group of volunteers of appropriate age, ethnicity, BMI, SES and parity will be recruited using resources of the NIH Office of Patient Recruitment (OPR) and AlescoData and will be a matched to study participants.
Who may be able to join
- Individuals of all races/ethnicities are eligible to participate.
- Individuals assigned female sex at birth ages >=18 to <= 99 years old who have not undergone medical and/or surgical transgender treatment
- Suspected maternal 45,X mosaicism as a secondary genomic finding following cfDNA sequencing during pregnancy
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Ability of subject to understand and the willingness to sign a written informed consent document.
- Ability to read and comprehend written and verbal English as the documents required for the study have not been translated for non-English speaking speakers.
Show all 11Show fewer
- Individuals assigned female sex at birth ages >=18 to <= 99 years old who have not undergone medical and/or surgical transgender treatment
- Good general health. In general, subjects should take no medications. The use of over the counter and prescription medications will be reviewed on a case-by-case basis; depending on the medication, subjects who have continued to take prescription medication prior to study entry may be still eligible.
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Ability of subject to understand and the willingness to sign a written informed consent document.
- Ability to read and comprehend written and verbal English as the documents required for the study have not been translated for non-English speaking speakers.
Who cannot join
- An individual who meets any of the following criteria at screening or baseline will be excluded from participation in this study:
- Male and transfemale individuals
- Individuals with significant medical comorbidities (e.g. NYHA Class III or IV heart failure, or CKD Stage 3b or worse (eGFR < 60 mL/min/1.73 m2), or American Society of Anesthesiologists Physical Status Class 3 or above) or other serious disorders at the discretion of the investigators.
- Individuals who have current substance abuse or a DSM 5 Axis I psychiatric disorder or DSM Axis II Mental Retardation diagnosis that in the opinion of the investigators would impede competence, compliance, or participation in the study
- Male and transfemale individuals
- Individuals with significant medical comorbidities (e.g. NYHA Class III or IV heart failure, or CKD Stage 3b or worse (eGFR < 60 mL/min/1.73 m2), or American Society of Anesthesiologists Physical Status Class 3 or above) or other serious disorders at the discretion of the investigators.
Show all 12Show fewer
- For females of reproductive potential: use of oral contraceptive pills, contraceptive patch, contraceptive vaginal ring within the past 3 months; use of depo medroxyprogesterone within the past 6 months; use of the etonorgestrel contraceptive implant within the past 1 month.
- Individuals who are pregnant, planning to become pregnant, currently nursing an infant, or have irregular menses, defined as cycles less than 21 days or greater than 45 days in premenopausal women.
- Previous history of the following: malignancy, chemotherapy, radiation therapy, primary ovarian insufficiency, galactosemia.
- Individuals who have current substance abuse or a DSM 5 Axis I psychiatric disorder or DSM Axis II Mental Retardation diagnosis that in the opinion of the investigators would impede competence, compliance, or participation in the study.
- Current use of tobacco or nicotine (eg. Nicotine patch, e-cigarette) products.
- Individuals who have had prior ear surgery other than myringotomy, individuals with cochlear implants, individuals who require use of hearing aids.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Implications of Maternal 45,X Mosaicism As A Secondary Genomic Finding Following Cell-free DNA Sequencing During Pregnancy: A Deep Phenotype Study
Background:
Mosaicism is a condition in which cells within the same person have a different genetic makeup. Sometimes, a type of mosaicism called 45,X may not be discovered in a woman until she undergoes routine tests during pregnancy. Little is known about how 45,X mosaicism may affect a person s long-term health.
Read more
Objective:
This natural history study will look for health risks in people with 45,X mosaicism.
Eligibility:
People aged 18 to 99 years who during pregnancy were found to have 45,X mosaicism. Healthy volunteers are also needed.
Design:
Participants will stay in the clinic for 2 days. They will have many tests:
A physical exam, including measurements of the body.
A gynecological exam, including genital measurements. Photos may be taken, with consent.
Blood tests, with blood drawn over an 8-week period. An oral glucose test for diabetes may also be done.
Tests of heart function. Participants will have small stickers attached to wires place on their chest, arms, and legs.
Hearing tests.
Ultrasound exams, which use echoing sound waves to create images of organs such as the heart and kidneys.
Imaging scans including x-rays, MRI, and DXA. The DXA uses x-rays to measure bone density and body fat. Other types of scans will capture images of the liver.
Participants will complete 4 surveys with questions about their sexual function, anxiety, depression, and health.
Participants may remain in the study for 20 years. For 5 years, they will have a yearly follow-up by phone or email. They may have follow-up visits at the clinic every 5 years.
Read the detailed description
Study Description:
This is a deep phenotype study of women who are determined to have 45,X mosaicism as a secondary genomic finding following cfDNA sequencing during pregnancy.
Objectives:
- To define and describe a comprehensive phenotype of women with confirmed 45,X mosaicism initially found by cfDNA including cardiovascular, skeletal, metabolic, reproductive, audiometric, immunologic, and psychological functions.
- To compare the comprehensive phenotype of women with confirmed 45,X mosaicism with a control population (a. age and BMI-matched female controls without 45, X mosaicism at the initial visit and b. NHANES age-and BMI-matched female data for the applicable year.)
- To explore changes in phenotype for both 45,X mosaicism and control groups with somatic loss of X chromosome over time.
Endpoints:
Primary Endpoint: (i) Hypertension (as defined in 2017 by the American College of Cardiology/American Heart Association (ACC/AHA)
Secondary Endpoints:
- Cardiovascular:
- Cardiac/coronary atherosclerosis
- Cardiac function, valve assessment, aortic anatomy, endothelial function
- Skeletal:
- Height
- Areal bone mineral density (aBMD) as per DXA
- Bone turnover markers
- Bone microarchitecture using trabecular bone score as per DXA
- Occult fractures using vertebral fracture assessment as per DXA
- Skeletal morphology for assessment of scoliosis
- Metabolic:
- Body fat distribution as per DXA
- Anthropometrics; Body weight; Waist to hip ratio
- Diabetes Mellitus
- Thyroid disorders
- Dyslipidemia
- Assessment of liver for fatty disease and fibrosis as per abdominal MRE/MRS
- Gynecologic and urologic:
- Markers of gonadal function and ovarian reserve
- Primary ovarian insufficiency, Infertility, Early menopause as per participant history
- Sexual function (as assessed by scores of the Female Sexual Function Index (FSFI) and the PROMIS(Registered Trademark) Sexual Function and Satisfaction Measures Version 2.0)
- Ovarian and uterine imaging as per pelvic ultrasound.
- Renal imaging as per renal ultrasound
- Obstetric: --Complications and outcomes of pregnancy as per participant history
- Audiometric: --Assessment of hearing loss
- Immunologic
- Immune biomarkers
- Celiac disease
- Psychological:
- PROMIS(Registered Trademark) Item Bank v1.0 - Emotional Distress - Anxiety - Short Form 8a
- PROMIS(Registered Trademark) Item Bank v.1.0 - Emotional Distress - Depression - Short Form 8b
- PROMIS(Registered Trademark) Scale v.1.2 - Global Health
Exploratory endpoints: Changes in phenotype (as outlined above) for both 45,X mosaicism and control groups with somatic loss of X chromosome over time.
- Conditions
- Cardiovascular Phenotype, Metabolic Phenotype, Hypertensive Disease, Psychological Phenotype, Audio
- Keywords
- Fetal Neonatal, Maternal, Turner Syndrome, Chromosomes, reproductive, Natural History
- Medical subject headings
- Hypertension, Turner Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Women who have submitted clinical samples for prenatal aneuploidy screening test with the finding of X mosaicism | |
| Group 2 (Control) | Control group of Female volunteers of appropriate age, ethnicity, BMI, SES and parity |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hypertension
Evaluation of hypertension as defined in 2017 by the American College of Cardiology/American Heart Association (ACC/AHA): Normal blood pressure - Systolic <120 mmHg and diastolic <80 mmHg
Measured: 5 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2022
- Study start1 Apr 2025
- Primary completion1 Apr 2025
- Study completion1 Apr 2025
Why it stopped: Study closed due to lack of resources. Study had no recruitment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiovascular PhenotypeStudies 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Veronica Gomez-Lobo, M.D., Principal investigator, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05548881
- Sponsor's protocol ID
- 10000137
- Other IDs
- 000137-CH
- Status last verified
- Apr 2025
- First submitted
- 17 Sep 2022
- Last updated
- 2 Apr 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Protocol does not specify IDP plans.
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Implications of Maternal 45,X Mosaicism As A Secondary Genomic Finding Following Cell-free DNA Sequencing During Pregnancy: A Deep Phenotype Study
- ClinicalTrials.gov ID
- NCT05548881
- Acronym / sponsor ID
- 10000137
- Conditions
- Cardiovascular Phenotype, Metabolic Phenotype, Hypertensive Disease, Psychological Phenotype, Audio
- Keywords
- Fetal Neonatal, Maternal, Turner Syndrome, Chromosomes, reproductive, Natural History
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: Study closed due to lack of resources. Study had no recruitment.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- 1 Apr 2025 (actual)
- Primary completion
- 1 Apr 2025 (actual)
- Study completion
- 1 Apr 2025 (actual)
- First posted
- 22 Sep 2022 (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.
Background:
Mosaicism is a condition in which cells within the same person have a different genetic makeup. Sometimes, a type of mosaicism called 45,X may not be discovered in a woman until she undergoes routine tests during pregnancy. Little is known about how 45,X mosaicism may affect a person s long-term health.
Objective:
This natural history study will look for health risks in people with 45,X mosaicism.
Eligibility:
People aged 18 to 99 years who during pregnancy were found to have 45,X mosaicism. Healthy volunteers are also needed.
Design:
Participants will stay in the clinic for 2 days. They will have many tests:
A physical exam, including measurements of the body.
A gynecological exam, including genital measurements. Photos may be taken, with consent.
Blood tests, with blood drawn over an 8-week period. An oral glucose test for diabetes may also be done.
Tests of heart function. Participants will have small stickers attached to wires place on their chest, arms, and legs.
Hearing tests.
Ultrasound exams, which use echoing sound waves to create images of organs such as the heart and kidneys.
Imaging scans including x-rays, MRI, and DXA. The DXA uses x-rays to measure bone density and body fat. Other types of scans will capture images of the liver.
Participants will complete 4 surveys with questions about their sexual function, anxiety, depression, and health.
Participants may remain in the study for 20 years. For 5 years, they will have a yearly follow-up by phone or email. They may have follow-up visits at the clinic every 5 years.
Detailed description
Study Description:
This is a deep phenotype study of women who are determined to have 45,X mosaicism as a secondary genomic finding following cfDNA sequencing during pregnancy.
Objectives:
- To define and describe a comprehensive phenotype of women with confirmed 45,X mosaicism initially found by cfDNA including cardiovascular, skeletal, metabolic, reproductive, audiometric, immunologic, and psychological functions.
- To compare the comprehensive phenotype of women with confirmed 45,X mosaicism with a control population (a. age and BMI-matched female controls without 45, X mosaicism at the initial visit and b. NHANES age-and BMI-matched female data for the applicable year.)
- To explore changes in phenotype for both 45,X mosaicism and control groups with somatic loss of X chromosome over time.
Endpoints:
Primary Endpoint: (i) Hypertension (as defined in 2017 by the American College of Cardiology/American Heart Association (ACC/AHA)
Secondary Endpoints:
- Cardiovascular:
- Cardiac/coronary atherosclerosis
- Cardiac function, valve assessment, aortic anatomy, endothelial function
- Skeletal:
- Height
- Areal bone mineral density (aBMD) as per DXA
- Bone turnover markers
- Bone microarchitecture using trabecular bone score as per DXA
- Occult fractures using vertebral fracture assessment as per DXA
- Skeletal morphology for assessment of scoliosis
- Metabolic:
- Body fat distribution as per DXA
- Anthropometrics; Body weight; Waist to hip ratio
- Diabetes Mellitus
- Thyroid disorders
- Dyslipidemia
- Assessment of liver for fatty disease and fibrosis as per abdominal MRE/MRS
- Gynecologic and urologic:
- Markers of gonadal function and ovarian reserve
- Primary ovarian insufficiency, Infertility, Early menopause as per participant history
- Sexual function (as assessed by scores of the Female Sexual Function Index (FSFI) and the PROMIS(Registered Trademark) Sexual Function and Satisfaction Measures Version 2.0)
- Ovarian and uterine imaging as per pelvic ultrasound.
- Renal imaging as per renal ultrasound
- Obstetric: --Complications and outcomes of pregnancy as per participant history
- Audiometric: --Assessment of hearing loss
- Immunologic
- Immune biomarkers
- Celiac disease
- Psychological:
- PROMIS(Registered Trademark) Item Bank v1.0 - Emotional Distress - Anxiety - Short Form 8a
- PROMIS(Registered Trademark) Item Bank v.1.0 - Emotional Distress - Depression - Short Form 8b
- PROMIS(Registered Trademark) Scale v.1.2 - Global Health
Exploratory endpoints: Changes in phenotype (as outlined above) for both 45,X mosaicism and control groups with somatic loss of X chromosome over time.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | – | –Women who have submitted clinical samples for prenatal aneuploidy screening test with the finding of X mosaicism |
| Group 2 (Control) | – | –Control group of Female volunteers of appropriate age, ethnicity, BMI, SES and parity |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Women who have submitted clinical samples for prenatal aneuploidy screening test with the finding of X mosaicism will be recruited from laboratories that offer cell-free DNA testing during pregnancy as well as nation-wide obstetricians and maternal-fetal-medicine specialists Potential participants are likely to be referred from specialists who care for them or will find the protocol through an internet search A control group of volunteers of appropriate age, ethnicity, BMI, SES and parity will be recruited using resources of the NIH Office of Patient Recruitment (OPR) and AlescoData and will be a matched to study participants.
Key inclusion criteria (11 listed)
- Individuals of all races/ethnicities are eligible to participate.
- Individuals assigned female sex at birth ages >=18 to <= 99 years old who have not undergone medical and/or surgical transgender treatment
- Suspected maternal 45,X mosaicism as a secondary genomic finding following cfDNA sequencing during pregnancy
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Ability of subject to understand and the willingness to sign a written informed consent document.
Key exclusion criteria (12 listed)
- An individual who meets any of the following criteria at screening or baseline will be excluded from participation in this study:
- Male and transfemale individuals
- Individuals with significant medical comorbidities (e.g. NYHA Class III or IV heart failure, or CKD Stage 3b or worse (eGFR < 60 mL/min/1.73 m2), or American Society of Anesthesiologists Physical Status Class 3 or above) or other serious disorders at the discretion of the investigators.
- Individuals who have current substance abuse or a DSM 5 Axis I psychiatric disorder or DSM Axis II Mental Retardation diagnosis that in the opinion of the investigators would impede competence, compliance, or participation in the study
- Male and transfemale individuals
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
Hypertension
Time frame: 5 Years
Evaluation of hypertension as defined in 2017 by the American College of Cardiology/American Heart Association (ACC/AHA): Normal blood pressure - Systolic <120 mmHg and diastolic <80 mmHg
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2025.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No. Protocol does not specify IDP plans.
Related trials for Cardiovascular Phenotype
Enrolling by invitationObservational study
Multi-Scale Analysis of Phenotypes in Heart Failure (MAP-HEART)
Heart Failure
RecruitingObservational study
Registry of Ehlers-Danlos Syndrome
Ehlers-Danlos Syndrome
Recruiting
Invasive Evaluation and Phenotype-Guided Treatment of ANOCA in Women
ANOCA - Angina With Non-obstructive Coronary Arteries, Coronary Microvascular Dysfunction (CMD)
RecruitingPhase 3
Pericardial Imaging Study
Pericarditis
Recruiting
Use of GeriKit to Better Phenotype Older Adults With Ischemic Heart Disease
Ischemic Heart Disease
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.
Veronica Gomez-Lobo, M.D. principal investigator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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 Cardiovascular Phenotype and Metabolic Phenotype, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site 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 11 inclusion and 12 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: withdrawn, as of the sponsor's last update on 2 Apr 2025. 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 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. 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 was withdrawn before enrolling participants, so there are no results.
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?
Hypertension (time frame: 5 Years). 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 2 Apr 2025.