Twin PlacentaNCT05733065
A Study of the Placental Methylome of Dichorionic and Monochorionic Monozygotic Twin Pairs to Establish a Timeline of Epigenetic Programming
A study testing saliva sample and questionnaire in people with Twin Placenta, run by University Hospital, Ghent at 1 site in Belgium.
Trial summary
The timing of the moment of splitting is variable amongst twins and can be inferred from chorionicity, allowing a time-line of early environmental influences to be established. Monozygotic twins can remain discordant for growth and health outcomes throughout life, implying the prenatal establishment of a regulatory… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Twin Placenta
- What is being tested?
- saliva sample and questionnaire
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 240 participants
- Where
- 1 siteBelgium
- Study dates
- 26 Jan 2021to 31 Dec 2025
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- natural conceived twin pairs born before 2002,
- with known birth weight, sex and gestational age,
- where both twins were live born without congenital abnormality
- Only pairs where both twins consent to inclusion in the study will be included.
Who cannot join
- Twins born after pregnancies complicated by conditions such as TTTS will be excluded.
Trial locations and contacts
1 site in 1 country.
About this study
The timing of the moment of splitting is variable amongst twins and can be inferred from chorionicity, allowing a time-line of early environmental influences to be established. Monozygotic twins can remain discordant for growth and health outcomes throughout life, implying the prenatal establishment of a regulatory program with effects that persist into adulthood.
Objective: To investigate the effect of the moment of splitting (chorionicity) on the placental and saliva (in adulthood) methylome and cardiometabolic disease risk in monozygotic twin pairs. Birth weight discordance will be used as an indicator of prenatal environmental heterogeneity between the twins.
Read the detailed description
Rationale: The developmental origins of health and disease (DoHaD) hypothesis, states that antenatal and early life exposure to a suboptimal environment can predispose for adverse health outcomes in adult life, such as cardiometabolic disease. Modification of the epigenome, and more specifically the methylome, seems a plausible mechanism for this. It has been shown that a suboptimal early environment, such as famine during the periconception period, can perturb DNA methylation signatures of the offspring. Furthermore, the preimplantation period is likely to represent a critical window for the establishment of optimal DNA methylation as epigenetic reprogramming takes place during this time. The precise influence of environmental factors during this time is incompletely understood; human studies of the preimplantation period are complicated by an inaccessibility of samples and the high variability of the environment induced by maternal factors. Here, the study of monozygotic twins can be employed. Although monozygotic twins are genetically identical, they can differ phenotypically, for example in birth weight. Phenotype and methylome differences attributable to genetic and maternal differences can be ruled out, meaning that intra-pair differences must be a result of variation in their prentatal environment. Furthermore, the moment of splitting defines the point from which twins can experience environmental differences. The timing of the moment of splitting is variable amongst twins and can be inferred from chorionicity, allowing a time-line of early environmental influences to be established. Monozygotic twins can remain discordant for growth and health outcomes throughout life, implying the prenatal establishment of a regulatory program with effects that persist into adulthood.
Objective: To investigate the effect of the moment of splitting (chorionicity) on the placental and saliva (in adulthood) methylome and cardiometabolic disease risk in monozygotic twin pairs. Birth weight discordance will be used as an indicator of prenatal environmental heterogeneity between the twins.
Study design: prospective twin cohort - using a subset of twins from the East Flanders Prospective Twin Study (EFPTS).
Main study parameters/endpoints: Placenta (birth) and saliva (adulthood) DNA methylation. Questionnaire-based adult anthropometric measurements and cardiometabolic disease risk data.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: There is no risk or benefit to participants associated with participation in this study as DNA methylation analyses cannot be used to identify disease (susceptibility). Placental tissue samples were already collected at birth and stored in a biobank. Further samples for DNA methylation analysis will be collected non-invasively by saliva sample. There is a minor time burden associated with participation in questionnaire-based data collection at the adult time point, however this is not expected to be excessive.
- Conditions
- Twin Placenta
- Being tested
- saliva sample, questionnaire
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
saliva sampleOther
Adult twins will be asked to send saliva samples in a reply envelope to Maastricht University, department of Genetics and Cell Biology, where they will be frozen and stored before analysis. DNA will be extracted from the saliva using a commercially available kit according to the manufacturer's instructions.
questionnaireOther
Along with saliva samples, adult twins, will be asked to complete a questionnaire about their health. Study subjects will be asked to self-report height and weight. Additionally, questions will focus on cardiometabolic risk, including questions about smoking, physical activities, medical diagnoses, current medications, family history of cardiometabolic disease, and for female twins an obstetric and gynaecological history, including number of pregnancies and pregnancy complications (such as gestational diabetes and pre-eclampsia). The questionnaire will take the form of a self-completed, web-based questionnaire which will be hosted by the Qualtrics platform (Qualtrics.com). This platform is supported by the University of Maastricht due to its security and privacy measures.
| Study group | Role | What they receive |
|---|---|---|
| Monozygotic Twin | Other | we will include natural conceived twin pairs born before 2002, with known birth weight, sex and gestational age, and where both twins were live born without congenital abnormality. Twins born after pregnancies complicated by conditions such as TTTS will be excluded. MZ twins pairs will be ranked according to intra-pair birth weight difference. Next, we intend to include the 120 most discordant monozygotic twin pairs, stratified by chorionicity (1:1 ratio) and in the case of DC by fusion of the placentas (1:1 ratio). Only pairs where both twins consent to inclusion in the study will be included. Receives: Other: saliva sample; Other: questionnaire |
What is being measured
The primary outcome is the main question the study is designed to answer.
To identify differences in DNA methylation in placental biopsy.
Placental DNA extraction will be carried out using a commercially available kit such as QIAamp DNA Mini Kit. We will first identify differences in placental DNA methylation that are associated with time-of splitting, i.e. chorionicity, to identify epigenome alterations that are attributable to the preimplantation period. Thereafter, birth weight discordance (weight of the heaver twin minus weight of the lighter twin, divided by weight of the heavier twin, multiplied by 100) will be used as a measure of antenatal environmental differences between the twins to identify loci of differential methylation that relate to environmental differences experienced in early gestation.
Measured: 1 year after saliva sample collection
To identify differences in DNA methylation in saliva sample.
Adult twins will be asked to send saliva samples. DNA will be extracted from the saliva using a commercially available kit. The adult methylome, deduced from saliva, will be interrogated to determine whether the methylation signatures associated with differences in the early embryonic environment persist into adulthood.
Measured: 1 year after saliva sample collection
Secondary outcomes (1)
To identify epigenetic alterations, present at birth that persist into adulthood, and predict growth/cardiometabolic disease risk parameters.
The adult outcomes, such as anthropometric measures and cardiometabolic disease risk factors, obtained from questionnaires will be used to develop a prediction model. The model will take into account biological data collected at birth as well as the placental methylome to predict growth and cardiometabolic outcomes in adulthood. For this purpose we will use techniques such as random forests, which use a fully annotated training dataset to classify subjects. Subsequently, further data points can be entered into the model, and will be assigned to the class that they most closely resemble.
Measured: 1 year after saliva sample collection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2023
- Study start26 Jan 2021
- Primary completion1 Feb 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Twin PlacentaStudies of the same condition, open and under way.
- More trials run by University Hospital, GhentThe 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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 240 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Ghent
- Sponsor type
- University, hospital or other
- Collaborators
- Maastricht University Medical Center
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05733065
- Sponsor's protocol ID
- BC-08264
- Status last verified
- Feb 2024
- First submitted
- 26 Jan 2021
- Last updated
- 29 Feb 2024
- 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 29 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of the Placental Methylome of Dichorionic and Monochorionic Monozygotic Twin Pairs to Establish a Timeline of Epigenetic Programming
- ClinicalTrials.gov ID
- NCT05733065
- Acronym / sponsor ID
- BC-08264
- Conditions
- Twin Placenta
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- University Hospital, GhentUniversity, hospital or other
- Collaborators
- Maastricht University Medical Center
- Study start
- 26 Jan 2021 (actual)
- Primary completion
- 1 Feb 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 17 Feb 2023 (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 timing of the moment of splitting is variable amongst twins and can be inferred from chorionicity, allowing a time-line of early environmental influences to be established. Monozygotic twins can remain discordant for growth and health outcomes throughout life, implying the prenatal establishment of a regulatory program with effects that persist into adulthood.
Objective: To investigate the effect of the moment of splitting (chorionicity) on the placental and saliva (in adulthood) methylome and cardiometabolic disease risk in monozygotic twin pairs. Birth weight discordance will be used as an indicator of prenatal environmental heterogeneity between the twins.
Detailed description
Rationale: The developmental origins of health and disease (DoHaD) hypothesis, states that antenatal and early life exposure to a suboptimal environment can predispose for adverse health outcomes in adult life, such as cardiometabolic disease. Modification of the epigenome, and more specifically the methylome, seems a plausible mechanism for this. It has been shown that a suboptimal early environment, such as famine during the periconception period, can perturb DNA methylation signatures of the offspring. Furthermore, the preimplantation period is likely to represent a critical window for the establishment of optimal DNA methylation as epigenetic reprogramming takes place during this time. The precise influence of environmental factors during this time is incompletely understood; human studies of the preimplantation period are complicated by an inaccessibility of samples and the high variability of the environment induced by maternal factors. Here, the study of monozygotic twins can be employed. Although monozygotic twins are genetically identical, they can differ phenotypically, for example in birth weight. Phenotype and methylome differences attributable to genetic and maternal differences can be ruled out, meaning that intra-pair differences must be a result of variation in their prentatal environment. Furthermore, the moment of splitting defines the point from which twins can experience environmental differences. The timing of the moment of splitting is variable amongst twins and can be inferred from chorionicity, allowing a time-line of early environmental influences to be established. Monozygotic twins can remain discordant for growth and health outcomes throughout life, implying the prenatal establishment of a regulatory program with effects that persist into adulthood.
Objective: To investigate the effect of the moment of splitting (chorionicity) on the placental and saliva (in adulthood) methylome and cardiometabolic disease risk in monozygotic twin pairs. Birth weight discordance will be used as an indicator of prenatal environmental heterogeneity between the twins.
Study design: prospective twin cohort - using a subset of twins from the East Flanders Prospective Twin Study (EFPTS).
Main study parameters/endpoints: Placenta (birth) and saliva (adulthood) DNA methylation. Questionnaire-based adult anthropometric measurements and cardiometabolic disease risk data.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: There is no risk or benefit to participants associated with participation in this study as DNA methylation analyses cannot be used to identify disease (susceptibility). Placental tissue samples were already collected at birth and stored in a biobank. Further samples for DNA methylation analysis will be collected non-invasively by saliva sample. There is a minor time burden associated with participation in questionnaire-based data collection at the adult time point, however this is not expected to be excessive.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Monozygotic Twin | Other | Other: saliva sample, Other: questionnairewe will include natural conceived twin pairs born before 2002, with known birth weight, sex and gestational age, and where both twins were live born without congenital abnormality. Twins born after pregnancies complicated by conditions such as TTTS will be excluded. MZ twins pairs will be ranked according to intra-pair birth weight difference. Next, we intend to include the 120 most discordant monozygotic twin pairs, stratified by chorionicity (1:1 ratio) and in the case of DC by fusion of the placentas (1:1 ratio). Only pairs where both twins consent to inclusion in the study will be included. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- natural conceived twin pairs born before 2002,
- with known birth weight, sex and gestational age,
- where both twins were live born without congenital abnormality
- Only pairs where both twins consent to inclusion in the study will be included.
Key exclusion criteria (1 listed)
- Twins born after pregnancies complicated by conditions such as TTTS will be excluded.
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 |
|---|---|---|
| saliva sampleAdult twins will be asked to send saliva samples in a reply envelope to Maastricht University, department of Genetics and Cell Biology, where they will be frozen and stored before analysis. DNA will be extracted from the saliva using a commercially available kit according to the manufacturer's instructions. | Other | Monozygotic Twin |
| questionnaireAlong with saliva samples, adult twins, will be asked to complete a questionnaire about their health. Study subjects will be asked to self-report height and weight. Additionally, questions will focus on cardiometabolic risk, including questions about smoking, physical activities, medical diagnoses, current medications, family history of cardiometabolic disease, and for female twins an obstetric and gynaecological history, including number of pregnancies and pregnancy complications (such as gestational diabetes and pre-eclampsia). The questionnaire will take the form of a self-completed, web-based questionnaire which will be hosted by the Qualtrics platform (Qualtrics.com). This platform is supported by the University of Maastricht due to its security and privacy measures. | Other | Monozygotic Twin |
Primary outcome
To identify differences in DNA methylation in placental biopsy.
Time frame: 1 year after saliva sample collection
Placental DNA extraction will be carried out using a commercially available kit such as QIAamp DNA Mini Kit. We will first identify differences in placental DNA methylation that are associated with time-of splitting, i.e. chorionicity, to identify epigenome alterations that are attributable to the preimplantation period. Thereafter, birth weight discordance (weight of the heaver twin minus weight of the lighter twin, divided by weight of the heavier twin, multiplied by 100) will be used as a measure of antenatal environmental differences between the twins to identify loci of differential methylation that relate to environmental differences experienced in early gestation.
To identify differences in DNA methylation in saliva sample.
Time frame: 1 year after saliva sample collection
Adult twins will be asked to send saliva samples. DNA will be extracted from the saliva using a commercially available kit. The adult methylome, deduced from saliva, will be interrogated to determine whether the methylation signatures associated with differences in the early embryonic environment persist into adulthood.
1 secondary outcome
To identify epigenetic alterations, present at birth that persist into adulthood, and predict growth/cardiometabolic disease risk parameters.
Time frame: 1 year after saliva sample collection
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Feb 2024.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing saliva sample and questionnaire in people with Twin Placenta, run by University Hospital, Ghent at 1 site in Belgium.
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 4 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: status not confirmed, as of the sponsor's last update on 29 Feb 2024. 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 Belgium. 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?
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?
To identify differences in DNA methylation in placental biopsy. (time frame: 1 year after saliva sample collection). The study lists 2 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 29 Feb 2024.