Fetal Origin of Adult DiseasesNCT02813746
Maternal Transcriptomic Regulation of the Preimplantation Embryo
An observational study of Fetal Origin of Adult Diseases, run by Igenomix at 1 site in Spain.
Trial summary
The aim of this study is to understand the epigenetic and transcriptomic mechanisms that regulate the fetal origin of adult diseases (FOAD), either for the presence of metabolic disorders in the future mothers, such as obesity or for the exposure to certain contaminants such as tobacco. 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
- Fetal Origin of Adult Diseases
- What is being tested?
- Fitness program, Stop smoking and Endometrial fluid collection
- Type of treatment
- Surgery or procedure, Lifestyle or therapy programme
- How many people
- 90 participants
- Where
- 1 siteSpain
- Study dates
- Apr 2016to 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 18 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Study population: Endometrial fluids from non-smoker obese and normoweight samples will be analysed in the window of implantation. In turn, endometrial fluids from normoweight smoker and non-smoker patients will be analysed in the window of implantation. These participants will be recruited in just one centre: IVI Valencia. Their recruitment will be done through a routine consultation carried out by the research team from the centre, as well as through the revision and daily evaluation of the medical reports and subsequent contact with those patients who could accomplish with the criteria selection and desire to be involved in the study.
Who may be able to join
- Women with age comprised between 18 and 45 years
- Normal uterus (evaluated trough ultrasound 2D/3D and/or hysteroscopy)
- Presence of at least one ovary
- Body mass index:
- Normoweight: 18.0-24.9 kg/m2 and non smokers
- Obese ≥30.0 kg/m2 and non smokers
- Smokers: Normoweight and smoke at least 10 cigarettes per day
Who cannot join
- Overweight=25.0-29.9 kg/m2
- Patients with Intrauterine device in the last 3 months
- Patients who had had hormonal contraceptives in the 2 previous months.
- Adnexal or uterine pathologies
- Polycystic ovary
- Existence of serious or uncontrolled bacterial, fungal or viral infections that could interfere with the involvement of the patient in the study or in the evaluation of the study results.
- Any disease or medical condition that could be unstable or could endanger the security of the patient and her compliance in the study.
Trial locations and contacts
1 site in 1 country.
Spain1 site, 1 recruiting
- Recruiting
IVI Valencia
Valencia, Valencia, 46015
Carlos Simon, MD PhD, +34963050900, carlos.simon@ivi.es
About this study
The aim of this study is to understand the epigenetic and transcriptomic mechanisms that regulate the fetal origin of adult diseases (FOAD), either for the presence of metabolic disorders in the future mothers, such as obesity or for the exposure to certain contaminants such as tobacco.
To do that, the miRNAs profiles secreted to the endometrial fluid in obese women vs normoweight women during the window of implantation will be identified. Likewise, it will be studied how that miRNA signature is normalized once a substantial loss of weight is produced by the patients involved in the studied. In parallel, a comparison of the miRNA expression profiles secreted in the endometrial fluid in smoker women vs nonsmoker women will be performed. As in the previous case, it will be studied if after the exposure to these contaminant, the normalization of the miRNA expression signature occurs. Finally, an in silico analysis will be carried out in order to define the target genes and the metabolic pathways affected by the miRNAs profile secreted in both pathological conditions
Read the detailed description
The developmental origins of adult disease are now recognized to be related to intrauterine conditions during embryonic and fetal life. Pregnancy begins with embryo implantation and its impact in adult life remains unknown. It has been demonstrated that human endometrial epithelium secretes specific microRNAs (miRNAs) during the time frame when the embryo enters the uterine cavity and initiates its adhesion to the uterine wall. Maternal miRNAs are secreted to the endometrial fluid, transported through exosomes or bound to proteins and consequently uptaken by the preimplantation embryo, before implantation occurs. As a consequence they suffer transcriptomic modifications that induce profound molecular and functional changes. The data already published demonstrate a novel paradigm: the transcriptomic maternal endometrial regulation of the pre-implantation embryo in health.
Here, this novel maternal endometrium-based mechanism will be applied in order to understand and prevent the developmental origin of adult diseases induced during embryonic implantation either by metabolic disorders of future mothers who have developed obesity or by the exposure to certain contaminants such as tobacco. In this project, the expression profiles of secreted miRNAs will be identified in the endometrial fluid in obese women compared to normo-weight women. Also, it will be studied how this "obese" endometrial miRNA pattern is reversed after weight-loss. In parallel, murine models of obesity will be used to proof this concept. In addition, the expression profiles of secreted endometrial miRNAs will be identified in smokers versus future non-smokers mothers. As in the previous case, the reversion of this signature will be analysed after stopping the exposure to this contaminant.
Then, "in silico" analysis will be done to select putative genes and functional pathways targeted by the signature of secreted endometrial miRNAs in the human and murine models in both pathological conditions. The determination of the transcriptomic and/or epigenome modifications induced by "obese" or/and "smoker" endometrial miRNAs in preimplantation mouse embryos is expected. As preliminary results, to support this project our accepted model of transcriptomic maternal endometrial regulation of the pre-implantation embryo in health, and the identification of a differential pattern of secreted miRNAs in the endometrial fluid of obese women compared to normo-weight counterparts is presented. In consequence, the application of this novel endometrium-based mechanism to the understanding and prevention of the origin of adult diseases related to obesity and/or tobacco exposure is proposed.
- Conditions
- Fetal Origin of Adult Diseases
- Being tested
- Fitness program, Stop smoking, Endometrial fluid collection
- Keywords
- Obesity, Tobacco, Epigenetic, Transcriptomic, microRNAs, miRNAs
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fitness programDietary supplement
Stop smokingBehavioural
Endometrial fluid collectionProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| Obese non smoker vs Normoweight non smoker | Endometrial fluid (EF) will be obtained from non-smokers normo-weight and obese patients in the receptive state. Samples will be collected 7 days after Luteinizing Hormone (LH) peak. They will be classified following the guidelines of the obesity classification system by the World Human Organization (WHO). Patients will be subjected to a fitness program during a year with the aim to achieve a weight reduction to normal values (19-24.9 kg/m2). The modifications in the miRNAs expression will be studied. After the weight loss, new EF will be collected from these patients. Receives: Dietary Supplement: Fitness program; Procedure: Endometrial fluid collection | |
| Normoweight smoker vs Normoweight non-smoker | EF will be obtained from non-smokers and smokers normo-weight in the receptive state. Samples will be collected 7 days after Luteinizing Hormone (LH) peak. Smokers patients will be urge to give up smoking during at least one year. After this time, new samples will be collected to determine if the non-exposition to this contaminant could exert any effect in the miRNAs signature. A regular control will be done in this group of patients to ensure that they have not been exposed to tobacco in 12 months. Professional support will be given in the same centre of the study to help the patient to accomplish its objective. Receives: Behavioral: Stop smoking; Procedure: Endometrial fluid collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Understanding of the epigenetic and transcriptomic mechanisms that regulate the FOAD
The main objective of the present project is focused on understanding the epigenetic and transcriptomic mechanisms that regulate the fetal origin of adult diseases (FOAD) either by the presence of metabolic disorders in mothers such as obesity, or by the exposure to certain pollutants such as tobacco
Measured: 40 months
Secondary outcomes (3)
Analysis of the miRNA expression pattern in the endometrial fluid (EF) in obese patients Analysis of the miRNA expression profile in the endometrial fluid
miRNA expression profile will be analysed in obese women , in comparison to normoweight women during the window of implantation. In turn, the normalization of this particular transcriptomic signature will be studied after the existence of a substantial loss of weight by the patients involved in the study.
Measured: 13 months
Analysis of the miRNA expression pattern in the endometrial fluid (EF) in smoker patients
A comparison between the miRNA expression profiles in smoker women vs. non-smoker will be done in the endometrial fluid (EF) during the window of implantation. As in the previous case, it will be studied if that particular pattern is normalized after giving up smoking.
Measured: 13 months
Functional analysis
The target genes and the metabolic routes affected by the miRNA profile secreted in both pathological conditions will be defined.
Measured: 13 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2016 (estimated)
- Study startApr 2016
- Primary completionApr 2017 (estimated)
- Study completionApr 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fetal Origin of Adult DiseasesStudies 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
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Igenomix
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Principal investigator, Carlos Simon, Igenomix
- Investigators
- Carlos Simón, MD PhD, Principal investigator, Igenomix
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02813746
- Sponsor's protocol ID
- 1603-IGX-018-CS
- Status last verified
- Jun 2016
- First submitted
- 22 Jun 2016
- Last updated
- 28 Jun 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Maternal Transcriptomic Regulation of the Preimplantation Embryo
- ClinicalTrials.gov ID
- NCT02813746
- Acronym / sponsor ID
- 1603-IGX-018-CS
- Conditions
- Fetal Origin of Adult Diseases
- Keywords
- Obesity, Tobacco, Epigenetic, Transcriptomic, microRNAs, miRNAs
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- IgenomixIndustry (pharma, biotech, devices)
- Study start
- Apr 2016
- Primary completion
- Apr 2017 (estimated)
- Study completion
- Apr 2019 (estimated)
- First posted
- 27 Jun 2016 (estimated)
- 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 study is to understand the epigenetic and transcriptomic mechanisms that regulate the fetal origin of adult diseases (FOAD), either for the presence of metabolic disorders in the future mothers, such as obesity or for the exposure to certain contaminants such as tobacco.
To do that, the miRNAs profiles secreted to the endometrial fluid in obese women vs normoweight women during the window of implantation will be identified. Likewise, it will be studied how that miRNA signature is normalized once a substantial loss of weight is produced by the patients involved in the studied. In parallel, a comparison of the miRNA expression profiles secreted in the endometrial fluid in smoker women vs nonsmoker women will be performed. As in the previous case, it will be studied if after the exposure to these contaminant, the normalization of the miRNA expression signature occurs. Finally, an in silico analysis will be carried out in order to define the target genes and the metabolic pathways affected by the miRNAs profile secreted in both pathological conditions
Detailed description
The developmental origins of adult disease are now recognized to be related to intrauterine conditions during embryonic and fetal life. Pregnancy begins with embryo implantation and its impact in adult life remains unknown. It has been demonstrated that human endometrial epithelium secretes specific microRNAs (miRNAs) during the time frame when the embryo enters the uterine cavity and initiates its adhesion to the uterine wall. Maternal miRNAs are secreted to the endometrial fluid, transported through exosomes or bound to proteins and consequently uptaken by the preimplantation embryo, before implantation occurs. As a consequence they suffer transcriptomic modifications that induce profound molecular and functional changes. The data already published demonstrate a novel paradigm: the transcriptomic maternal endometrial regulation of the pre-implantation embryo in health.
Here, this novel maternal endometrium-based mechanism will be applied in order to understand and prevent the developmental origin of adult diseases induced during embryonic implantation either by metabolic disorders of future mothers who have developed obesity or by the exposure to certain contaminants such as tobacco. In this project, the expression profiles of secreted miRNAs will be identified in the endometrial fluid in obese women compared to normo-weight women. Also, it will be studied how this "obese" endometrial miRNA pattern is reversed after weight-loss. In parallel, murine models of obesity will be used to proof this concept. In addition, the expression profiles of secreted endometrial miRNAs will be identified in smokers versus future non-smokers mothers. As in the previous case, the reversion of this signature will be analysed after stopping the exposure to this contaminant.
Then, "in silico" analysis will be done to select putative genes and functional pathways targeted by the signature of secreted endometrial miRNAs in the human and murine models in both pathological conditions. The determination of the transcriptomic and/or epigenome modifications induced by "obese" or/and "smoker" endometrial miRNAs in preimplantation mouse embryos is expected. As preliminary results, to support this project our accepted model of transcriptomic maternal endometrial regulation of the pre-implantation embryo in health, and the identification of a differential pattern of secreted miRNAs in the endometrial fluid of obese women compared to normo-weight counterparts is presented. In consequence, the application of this novel endometrium-based mechanism to the understanding and prevention of the origin of adult diseases related to obesity and/or tobacco exposure is proposed.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Obese non smoker vs Normoweight non smoker | – | Dietary Supplement: Fitness program, Procedure: Endometrial fluid collectionEndometrial fluid (EF) will be obtained from non-smokers normo-weight and obese patients in the receptive state. Samples will be collected 7 days after Luteinizing Hormone (LH) peak. They will be classified following the guidelines of the obesity classification system by the World Human Organization (WHO). Patients will be subjected to a fitness program during a year with the aim to achieve a weight reduction to normal values (19-24.9 kg/m2). The modifications in the miRNAs expression will be studied. After the weight loss, new EF will be collected from these patients. |
| Normoweight smoker vs Normoweight non-smoker | – | Behavioral: Stop smoking, Procedure: Endometrial fluid collectionEF will be obtained from non-smokers and smokers normo-weight in the receptive state. Samples will be collected 7 days after Luteinizing Hormone (LH) peak. Smokers patients will be urge to give up smoking during at least one year. After this time, new samples will be collected to determine if the non-exposition to this contaminant could exert any effect in the miRNAs signature. A regular control will be done in this group of patients to ensure that they have not been exposed to tobacco in 12 months. Professional support will be given in the same centre of the study to help the patient to accomplish its objective. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Endometrial fluids from non-smoker obese and normoweight samples will be analysed in the window of implantation. In turn, endometrial fluids from normoweight smoker and non-smoker patients will be analysed in the window of implantation. These participants will be recruited in just one centre: IVI Valencia. Their recruitment will be done through a routine consultation carried out by the research team from the centre, as well as through the revision and daily evaluation of the medical reports and subsequent contact with those patients who could accomplish with the criteria selection and desire to be involved in the study.
Key inclusion criteria (7 listed)
- Women with age comprised between 18 and 45 years
- Normal uterus (evaluated trough ultrasound 2D/3D and/or hysteroscopy)
- Presence of at least one ovary
- Body mass index:
- Normoweight: 18.0-24.9 kg/m2 and non smokers
Key exclusion criteria (7 listed)
- Overweight=25.0-29.9 kg/m2
- Patients with Intrauterine device in the last 3 months
- Patients who had had hormonal contraceptives in the 2 previous months.
- Adnexal or uterine pathologies
- Polycystic ovary
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 |
|---|---|---|
| Fitness program | Dietary supplement | Obese non smoker vs Normoweight non smoker |
| Stop smoking | Behavioural | Normoweight smoker vs Normoweight non-smoker |
| Endometrial fluid collection | Procedure or surgery | Normoweight smoker vs Normoweight non-smoker, Obese non smoker vs Normoweight non smoker |
Primary outcome
Understanding of the epigenetic and transcriptomic mechanisms that regulate the FOAD
Time frame: 40 months
The main objective of the present project is focused on understanding the epigenetic and transcriptomic mechanisms that regulate the fetal origin of adult diseases (FOAD) either by the presence of metabolic disorders in mothers such as obesity, or by the exposure to certain pollutants such as tobacco
3 secondary outcomes
Analysis of the miRNA expression pattern in the endometrial fluid (EF) in obese patients Analysis of the miRNA expression profile in the endometrial fluid
Time frame: 13 months
Analysis of the miRNA expression pattern in the endometrial fluid (EF) in smoker patients
Time frame: 13 months
Functional analysis
Time frame: 13 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2016.
- Individual participant dataSharing planned: No
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.
Carlos Simón, MD PhD principal investigator
Igenomix
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 Fetal Origin of Adult Diseases, run by Igenomix at 1 site in Spain.
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 7 inclusion and 7 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 28 Jun 2016. 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 Spain. 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 Carlos Gomez, BSc MSc (+34963905310, carlos.gomez@igenomix.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Understanding of the epigenetic and transcriptomic mechanisms that regulate the FOAD (time frame: 40 months). 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 28 Jun 2016.