A Study of Multilocus Methylation Abnormalities in Subjects With Imprinting Disorders (ImprintiNG)

March 23, 2026 updated by: Assistance Publique - Hôpitaux de Paris
Imprinting disorders may be caused by epimutations. Some subjects exhibit methylation abnormalities in several regions subject to imprinting, a condition known as multilocus imprinting disorder (MLID). The prevalence of MLID is unknown, due to variations in the methodologies used (including technique employed and number of regions studied). The phenotypic consequences of MLID are also poorly understood. Studying the methylation of all the imprinted regions would make it possible to determine the prevalence of MLID as well as its clinical consequences.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Imprinting disorders may be secondary to various molecular mechanisms, including "epimutations", i.e. aberrant methylation levels (gain or loss of methylation) at the level of the ICRs. The 11p15 region in humans contains two genes essential for controlling foetal growth: IGF2, expressed from the paternal allele, and whose expression is controlled by an imprinting centre called H19/IGF2: IG-DMR (or ICR1), methylated on the paternal allele; and CDKN1C, expressed from the maternal allele, and whose expression is controlled by a second imprinting centre called KCNQ1OT1:TSS-DMR (or ICR2), methylated on the maternal allele. (Eggermann et al, 2023) Among the diseases linked to parental imprinting, Beckwith Wiedemann syndrome (BWS, prevalence 1/13,500) is an overgrowth syndrome that, in particular, predisposes to the appearance of embryonic tumours during the first years of life. 80% of subjects with BWS have an alteration in the 11p15 region, which may be a loss of ICR2 methylation (around 50%) or a gain of ICR1 methylation (5 to 10%). (Brioude et al, 2018) Silver Russell syndrome (SRS, prevalence 1/50,000) is a syndrome of fetal and postnatal growth restriction, with preservation of head circumference, severe feeding difficulties and early metabolic complications. Approximately 50% of subjects with SRS have a loss of ICR1 methylation in the 11p15 region. (Wakeling et al, 2017). Temple syndrome (TS14) is a fetal and postnatal growth restriction syndrome similar to SRS with neonatal hypotonia, and associated with a risk of early puberty and obesity. This syndrome is usually caused by abnormalities of the 14q32 region at the MEG3/DLK1 locus which is also imprinted (maternal uniparental disomy, paternal deletion or loss of methylation of the MEG3/DLK1:IG-DMR). (Geoffron et al, 2017) For several years now, it has been shown that some subjects with a methylation anomaly at one locus may have methylation anomalies at other regions subject to parental imprinting. This condition is known as multilocus imprinting disorder (MLID). The prevalence of this multilocus disorder is not precisely known, because the methodologies used vary in terms of the technique used and the number of DMRs studied. In some subjects, symptoms of different diseases linked to these different regions may be present. However, little is currently known about the phenotypic consequences of these multilocus disorders. Finally, although most methylation anomalies occur sporadically, a few familial forms of methylation anomalies have been reported, with the common feature of recurrent miscarriages and the presence of multilocus disease in affected subjects. These familial forms have been associated with the presence in the mother of pathogenic variations in the genes encoding factors in the SCMC (subcortical maternal complex). Among other things, these factors are involved in oocyte maturation and the regulation of epigenetic marks after fertilisation and during the first cell divisions. (MacKay et al, 2024)

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
96

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • France
      • Paris, France, 75012
        • Molecular Endocrinology and Imprinting disorder department - Trousseau Hospital
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. "Negative control" population: subjects who have undergone genetic exploration and:

    • Having had a study of normal methylation of the 11p15 region (H19/IGF2: IG-DMR and KCNQ1OT1:TSS-DMR) by the reference technique.
    • And having had a sequencing study of one or more genes involved in a growth pathology (Sanger sequencing and/or NGS analysis) and having concluded in the presence of a pathogenic variant responsible for the pathology.

    OR

    Study population:

    - subjects who had undergone a reference genetic investigation (ASMM-RTqPCR) and for whom the final diagnosis was: gain or loss of methylation at the H19/IGF2:IG-DMR locus (BWS,SRS), at the KCNQ1OT1:TSS-DMR locus (BWS) or at the DLK1/MEG3:IG-DMR locus (TS14).

  2. Affiliation with a social security scheme or beneficiary (excluding AME).
  3. Signature of the consent form by the subject's parents or guardians, or the subject if of age at the time of the study.

Exclusion Criteria:

  • Inability of either the subject (if over 18) or the parents or holder of parental authority to receive informed information about the protocol.
  • Subject (if over 18) or parent or holder of parental authority deprived of their liberty by judicial or administrative decision

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
No Intervention: Negative control group
Control subjects from the DNA bank, subjects with normal methylation analysis using the reference technique, for whom the final diagnosis is a genetic rather than an epigenetic cause. This population will allow the establishment of normal reference values for the methylation index for each DMR studied using the newly developed technique.
Experimental: Study population
Subjects with a methylation anomaly in a previously identified imprinted region using the reference technique
Other: Methylation study
Methylation study by high-throughput sequencing technique after enzymatic DNA treatment and DMR capture

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
To validate the ability of a new technique (ImprintCap) to detect abnormal methylation levels from a population for which a methylation anomaly has been detected at a region by the reference technique.
Time Frame: 30 month (end of the study)
Methylation index reference values for each DMR will be established from the 24 negative control subjects.
30 month (end of the study)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
To determine the proportion (%) of subjects with multilocus disease in the study population.
Time Frame: 30 month (end of the study)
In the study population, the methylation indices of each DMR determined by the MethylCap technique will be compared with reference values: multilocus disease will be defined by the presence of a methylation index greater than +3 SDS (methylation gain) or less than -3 SDS (methylation loss) at least one other DMR compared with the established reference values.
30 month (end of the study)
To compare the phenotypic data (clinical and/or biological) collected during the usual follow-up consultations in the population of subjects with or without multilocus disease.
Time Frame: 30 month (end of the study)
Association between the clinical and biological data of the study population according to the presence or absence of multilocus disease.
30 month (end of the study)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assistance Publique - Hôpitaux de Paris

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Frédéric Brioude, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 23, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 23, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 27, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 27, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 23, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • APHP251316
  • IDRCB 2025-A01991-48 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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