Neurodevelopmental DisabilitiesNCT05004090
Emotional Regulation in Children With ND: the Role of Genomic Variation, Proteomic Patterns, and Early Experience
An observational study of Neurodevelopmental Disabilities and Emotional Regulation, run by IRCCS Eugenio Medea at 1 site in Italy.
Trial summary
Children with neurodevelopmental disabilities (ND) represent an heterogeneous population characterized by a wide range of clinical diagnoses (e.g., cerebral palsy, sensory impairment, psychomotor retardation), which are associated with various deficits that emerge early in the child's life. Read more about this study
- Who is it for?
- Ages 3 to 24 monthsHealthy volunteers can take part
- Conditions the study is for
- Neurodevelopmental Disabilities, Emotional Regulation, Epigenetics
- What is being tested?
- DNA methylation analysis, Proteomics analysis and Still Face Paradigm
- How many people
- 248 participants
- Where
- 1 siteItaly
- Study dates
- 7 Apr 2021to 31 Dec 2023
- 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 3 to 24 months
- All sexes
- Healthy volunteers accepted
- Child
Study population: Children with ND and their mothers will be recruited through consecutive and convenience sampling at the U.O.C. "Specialistic Rehabilitation - Neuropsychiatric Pathologies of Developmental Age" and the U.O.C. "Functional Rehabilitation" of the Scientific Institute "E. Medea" (Bosisio Parini site). Children with typical development and their mothers will be recruited from nursery schools in the province of Lecco. After viewing an informative letter describing the general research, mothers will be contacted by telephone and invited to participate voluntarily.
Who may be able to join
- Children with ND:
- Age between 3 and 24 months (chronologically or corrected in the case of children born preterm);
- mild to moderate developmental delay documented by clinical signs (e.g., symptoms of brain injury on neurological examination or neuroimaging) or by developmental scales (i.e., Griffiths III scales) associated with various diagnoses (e.g., cerebral palsy, prematurity);
- absence of genetic syndromes. The Griffiths III scale will be used to assess the child's overall level of development.
- Typical developmental children:
- birth to term;
Show all 14Show fewer
- age between 3 and 24 months (chronological);
- absence of peri- or postnatal pathology.
- Inclusion criteria for mothers (DN and typical development):
- age above 18 years;
- good understanding of the Italian language;
- absence of cognitive difficulties and/or psychiatric disorders;
- no intake of psychotropic medications;
- not part of a single-parent family.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
IRCCS E. Medea
Bosisio Parini, Lecco, 23842
Rosario Montirosso, +39031877494, rosario.montirosso@lanostrafamiglia.it
About this study
Official title: Emotional-behavioral Regulation in Children With Neurodevelopmental Disabilities: an Exploratory Investigation of the Role of Genomic Variation, Proteomic Patterns, and Quality of Early Experience
Children with neurodevelopmental disabilities (ND) represent an heterogeneous population characterized by a wide range of clinical diagnoses (e.g., cerebral palsy, sensory impairment, psychomotor retardation), which are associated with various deficits that emerge early in the child's life. Although it has been broadly demonstrated that children with ND exhibit several differences in social-emotional skills and emotional-behavioral regulation, the underlying mechanisms that are associated with more or less impaired developmental trajectories remain still partially unexplored. While several studies have investigated the role of biological and environmental factors in the emotional behavioral regulation of typically developing children or children with risk conditions other than ND (e.g., children who are victims of maltreatment), little research has jointly explored the role of methylation, polymorphisms, and environmental experience in the emotional-behavioral regulation of children with ND during the first years of life. The aim of this project is to investigate biological (DNA methylation, polymorphic variants, and proteomics) and environmental (e.g., painful and/or invasive nursing procedures, proximity, and physical contact) factors that might be associated with the emotional behavioral regulation of children with ND.
Read the detailed description
Background: Children with neurodevelopmental disabilities (ND) are an heterogeneous population characterized by a wide variety of clinical diagnoses, which are associated with different deficits that emerge during infancy and childhood. Although diagnostic framing may vary, several studies observed that children with ND share reduced social-relational skills, characterized by lower interactive and dyadic attention skills and decreased use of interpersonal communication cues. Although it has been broadly demonstrated that children with ND exhibit several differences in social-emotional skills and emotional behavioral regulation, the underlying mechanisms that are associated with more or less impaired trajectories remain partially unexplored.
Primary aim: to explore in a sample of children with ND aged 3 to 24 months the contribution of 1) methylation of candidate genes (e.g., OXTR, SLC6A4, BDNF, and DRD4), 2) polymorphisms in emotional-behavioral regulation, and 3) environmental experience (i.e., adverse experiences and quality of parental behavior) in emotional-behavioral regulation.
Secondary aim: 1) to explore a possible association between proteomics and emotional-behavioral regulation in a sample of children with ND aged between 3 and 24 months; 2) to identify functional and structural patterns of candidate genes associated with emotional behavioral regulation by applying a computational approach. Modules of genes potentially associated with social-emotional development in networks of interaction and spatio-temporal co-expression in the encephalon will also be identified.
Planned Activities:
Methods:the project involves a clinical group of children with ND and their mothers and a control group of typically developing children and their mothers. Because of the nature of the groups, the study is a quasi-experimental research design.
The study involves the following procedures:
- collection of biological material: saliva collection using non-invasive modalities and the Oragene OG575 kit (Genotek DNA) and urine collection using non-invasive modalities.
- administration of questionnaires and diary of proximity: the mother (both for the clinical group and for the control group) will be asked to fill out some questionnaires relating to their mood, habitual behavior and development of the child. It will also be evaluated how much and in what way the mother spends in physical contact (e.g. time spent caressing the baby; time spent holding the baby; time spent when the baby is attached to the mother's breast). This data will be derived through the use of a repurposed version of Raiskila et al.'s "closeness diary" implemented in an electronic format, in the form of an APP (APP: inContatto);
- videotaping the Parent-Child Interaction in a semi-structured context in 5 different phases in accordance with the Still Face paradigm (Tronick et al., 1978): Play, Still#1, Reunion#1, Still#2, Reunion#2.
Interactions will be videotaped for subsequent behavioral coding using various coding tools. The child's emotional-behavioral regulation will be coded using the coding systems: a) Infant and Caregiver Engagement Phase, b) Infant Regulatory Scoring System and Maternal Regulatory Scoring System by Tronik. In addition, infant and maternal behavior will be coded using the Global Rating Scale coding system by Murray and maternal touch behavior using the Maternal Touch Coding System by Provenzi.
- Being tested
- DNA methylation analysis, Proteomics analysis, Still Face Paradigm
- Medical subject headings
- Emotional Regulation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DNA methylation analysisDiagnostic test
Genomic DNA will be extracted from 0.4 ml aliquots of each saliva sample using the kit manufacturer's suggested protocol, quantified with Qubit 2.0 (Invitrogen), and stored at -20°C. Aliquots of 250 ng of each DNA will be edited for methylation analysis with the EZ DNA Methylation Lightning kit (Zymo Research). Amplification of samples and their preparation for NGS sequencing will be performed as described. Samples will be sequenced on NextSeq 500 (Illumina). Individual processed sequences (PE reads) will be independently aligned to reference sequences using a parallel Smith-Waterman algorithm. Only reads that consistently align to the same reference sequence will be retained. At each CpG site in each analyzed sequence, the frequencies of the four bases will be evaluated and tabulated.
Proteomics analysisDiagnostic test
Urine samples are collected using non-invasive methods and are prepared according to a procedure preparatory to quantitative recovery of exosomes: once thawed and centrifuged at 17,000 x g for 10 min at 4°C, the recovered supernatants are separated and centrifuged at 200,000 x g for 1 hr at 4°C. Exosome pellets are separated, washed repeatedly and resuspended in buffer (NH4HCO3, 0.1 mM ph=7.8). Protein concentration is estimated with the SPNTM Protein Assay kit and each sample (50 ± 0.5 μg protein) is digested with trypsin using a 1:50 (w/w) enzyme/substrate ratio at 37 °C over night (o/w). A second tryptic digestion is performed with an enzyme:substrate ratio of 1:100 (w/w) for 4h. Digested samples, centrifuged at 13,000 × g for 10 min, are purified and concentrated using PepClean C-18 columns. The samples obtained are analyzed by reversed-phase liquid chromatography coupled to high-resolution mass spectrometry.
Still Face ParadigmDiagnostic test
During an observational session, a short video recording of the mother-child interaction of approximately 10 minutes will be made in a semi-structured setting to assess the child's emotional regulation and social behavior. The interaction will be structured in 5 different phases according to the Still Face paradigm (Tronick et al., 1978): Play, Still#1, Reunion#1, Still#2, Reunion#2. Play: Mothers will be invited to interact with their babies for 10 minutes; Still: mothers will be asked to remain still while maintaining an unresponsive expressionless face and not to smile, touch, or talk to the child for 2 minutes (Still#1: 2 minutes; Still#2: 2 minutes); Reunion: mothers will be asked to resume the play activity with their own for an additional 2 minutes (Reunion#1: 2 minutes; Reunion#2: 2 minutes).
| Study group | Role | What they receive |
|---|---|---|
| children with ND | children with neurodevelopmental disabilities (ND) age between 3 and 24 months (chronologically or corrected in the case of children born preterm). Receives: Diagnostic Test: DNA methylation analysis; Diagnostic Test: Proteomics analysis; Diagnostic Test: Still Face Paradigm | |
| Typical developed children (TD) | children with typical development age between 3 and 24 months (chronological). Receives: Diagnostic Test: DNA methylation analysis; Diagnostic Test: Proteomics analysis; Diagnostic Test: Still Face Paradigm |
What is being measured
The primary outcome is the main question the study is designed to answer.
Infant DNA methylation status
The DNA methylation status (i.e. percentage) of candidate genes (e.g., OXTR, SLC6A4, BDNF, and DRD4) will be assessed from salivary samples obtained from infants.
Measured: 1 day , at the recruitment
Infant behavioral regulation
The infant behavioral regulation (i.e., negative emotionality) will be coded micro-analitically (i.e., second-by-second) from videotapes of mother-infant interactions.
Measured: 1 day , at the recruitment
Secondary outcomes (1)
Infant proteomic patterns
Proteomic patterns will be evaluated for the relative amount and post-translational modifications of candidate proteins, thought to be involved with the stress response in infants.
Measured: 1 day , at the recruitment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2021
- Study start7 Apr 2021
- Primary completion30 Nov 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neurodevelopmental DisabilitiesStudies of the same condition, open and under way.
- More trials run by IRCCS Eugenio MedeaThe 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
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 248 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS Eugenio Medea
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05004090
- Sponsor's protocol ID
- RC2021_820
- Status last verified
- Oct 2023
- First submitted
- 30 Jul 2021
- Last updated
- 18 Oct 2023
- 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 18 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Emotional-behavioral Regulation in Children With Neurodevelopmental Disabilities: an Exploratory Investigation of the Role of Genomic Variation, Proteomic Patterns, and Quality of Early Experience
- ClinicalTrials.gov ID
- NCT05004090
- Acronym / sponsor ID
- RC2021_820
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 248 participants (estimated)
- Lead sponsor
- IRCCS Eugenio MedeaUniversity, hospital or other
- Study start
- 7 Apr 2021 (actual)
- Primary completion
- 30 Nov 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 13 Aug 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.
Children with neurodevelopmental disabilities (ND) represent an heterogeneous population characterized by a wide range of clinical diagnoses (e.g., cerebral palsy, sensory impairment, psychomotor retardation), which are associated with various deficits that emerge early in the child's life. Although it has been broadly demonstrated that children with ND exhibit several differences in social-emotional skills and emotional-behavioral regulation, the underlying mechanisms that are associated with more or less impaired developmental trajectories remain still partially unexplored. While several studies have investigated the role of biological and environmental factors in the emotional behavioral regulation of typically developing children or children with risk conditions other than ND (e.g., children who are victims of maltreatment), little research has jointly explored the role of methylation, polymorphisms, and environmental experience in the emotional-behavioral regulation of children with ND during the first years of life. The aim of this project is to investigate biological (DNA methylation, polymorphic variants, and proteomics) and environmental (e.g., painful and/or invasive nursing procedures, proximity, and physical contact) factors that might be associated with the emotional behavioral regulation of children with ND.
Detailed description
Background: Children with neurodevelopmental disabilities (ND) are an heterogeneous population characterized by a wide variety of clinical diagnoses, which are associated with different deficits that emerge during infancy and childhood. Although diagnostic framing may vary, several studies observed that children with ND share reduced social-relational skills, characterized by lower interactive and dyadic attention skills and decreased use of interpersonal communication cues. Although it has been broadly demonstrated that children with ND exhibit several differences in social-emotional skills and emotional behavioral regulation, the underlying mechanisms that are associated with more or less impaired trajectories remain partially unexplored.
Primary aim: to explore in a sample of children with ND aged 3 to 24 months the contribution of 1) methylation of candidate genes (e.g., OXTR, SLC6A4, BDNF, and DRD4), 2) polymorphisms in emotional-behavioral regulation, and 3) environmental experience (i.e., adverse experiences and quality of parental behavior) in emotional-behavioral regulation.
Secondary aim: 1) to explore a possible association between proteomics and emotional-behavioral regulation in a sample of children with ND aged between 3 and 24 months; 2) to identify functional and structural patterns of candidate genes associated with emotional behavioral regulation by applying a computational approach. Modules of genes potentially associated with social-emotional development in networks of interaction and spatio-temporal co-expression in the encephalon will also be identified.
Planned Activities:
Methods:the project involves a clinical group of children with ND and their mothers and a control group of typically developing children and their mothers. Because of the nature of the groups, the study is a quasi-experimental research design.
The study involves the following procedures:
- collection of biological material: saliva collection using non-invasive modalities and the Oragene OG575 kit (Genotek DNA) and urine collection using non-invasive modalities.
- administration of questionnaires and diary of proximity: the mother (both for the clinical group and for the control group) will be asked to fill out some questionnaires relating to their mood, habitual behavior and development of the child. It will also be evaluated how much and in what way the mother spends in physical contact (e.g. time spent caressing the baby; time spent holding the baby; time spent when the baby is attached to the mother's breast). This data will be derived through the use of a repurposed version of Raiskila et al.'s "closeness diary" implemented in an electronic format, in the form of an APP (APP: inContatto);
- videotaping the Parent-Child Interaction in a semi-structured context in 5 different phases in accordance with the Still Face paradigm (Tronick et al., 1978): Play, Still#1, Reunion#1, Still#2, Reunion#2.
Interactions will be videotaped for subsequent behavioral coding using various coding tools. The child's emotional-behavioral regulation will be coded using the coding systems: a) Infant and Caregiver Engagement Phase, b) Infant Regulatory Scoring System and Maternal Regulatory Scoring System by Tronik. In addition, infant and maternal behavior will be coded using the Global Rating Scale coding system by Murray and maternal touch behavior using the Maternal Touch Coding System by Provenzi.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| children with ND | – | Diagnostic Test: DNA methylation analysis, Diagnostic Test: Proteomics analysis, Diagnostic Test: Still Face Paradigmchildren with neurodevelopmental disabilities (ND) age between 3 and 24 months (chronologically or corrected in the case of children born preterm). |
| Typical developed children (TD) | – | Diagnostic Test: DNA methylation analysis, Diagnostic Test: Proteomics analysis, Diagnostic Test: Still Face Paradigmchildren with typical development age between 3 and 24 months (chronological). |
Who may qualify
- Ages
- 3 to 24 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- Children with ND and their mothers will be recruited through consecutive and convenience sampling at the U.O.C. "Specialistic Rehabilitation - Neuropsychiatric Pathologies of Developmental Age" and the U.O.C. "Functional Rehabilitation" of the Scientific Institute "E. Medea" (Bosisio Parini site). Children with typical development and their mothers will be recruited from nursery schools in the province of Lecco. After viewing an informative letter describing the general research, mothers will be contacted by telephone and invited to participate voluntarily.
Key inclusion criteria (14 listed)
- Age between 3 and 24 months (chronologically or corrected in the case of children born preterm);
- mild to moderate developmental delay documented by clinical signs (e.g., symptoms of brain injury on neurological examination or neuroimaging) or by developmental scales (i.e., Griffiths III scales) associated with various diagnoses (e.g., cerebral palsy, prematurity);
- absence of genetic syndromes. The Griffiths III scale will be used to assess the child's overall level of development.
- birth to term;
- age between 3 and 24 months (chronological);
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| DNA methylation analysisGenomic DNA will be extracted from 0.4 ml aliquots of each saliva sample using the kit manufacturer's suggested protocol, quantified with Qubit 2.0 (Invitrogen), and stored at -20°C. Aliquots of 250 ng of each DNA will be edited for methylation analysis with the EZ DNA Methylation Lightning kit (Zymo Research). Amplification of samples and their preparation for NGS sequencing will be performed as described. Samples will be sequenced on NextSeq 500 (Illumina). Individual processed sequences (PE reads) will be independently aligned to reference sequences using a parallel Smith-Waterman algorithm. Only reads that consistently align to the same reference sequence will be retained. At each CpG site in each analyzed sequence, the frequencies of the four bases will be evaluated and tabulated. | Diagnostic test | Typical developed children (TD), children with ND |
| Proteomics analysisUrine samples are collected using non-invasive methods and are prepared according to a procedure preparatory to quantitative recovery of exosomes: once thawed and centrifuged at 17,000 x g for 10 min at 4°C, the recovered supernatants are separated and centrifuged at 200,000 x g for 1 hr at 4°C. Exosome pellets are separated, washed repeatedly and resuspended in buffer (NH4HCO3, 0.1 mM ph=7.8). Protein concentration is estimated with the SPNTM Protein Assay kit and each sample (50 ± 0.5 μg protein) is digested with trypsin using a 1:50 (w/w) enzyme/substrate ratio at 37 °C over night (o/w). A second tryptic digestion is performed with an enzyme:substrate ratio of 1:100 (w/w) for 4h. Digested samples, centrifuged at 13,000 × g for 10 min, are purified and concentrated using PepClean C-18 columns. The samples obtained are analyzed by reversed-phase liquid chromatography coupled to high-resolution mass spectrometry. | Diagnostic test | Typical developed children (TD), children with ND |
| Still Face ParadigmDuring an observational session, a short video recording of the mother-child interaction of approximately 10 minutes will be made in a semi-structured setting to assess the child's emotional regulation and social behavior. The interaction will be structured in 5 different phases according to the Still Face paradigm (Tronick et al., 1978): Play, Still#1, Reunion#1, Still#2, Reunion#2. Play: Mothers will be invited to interact with their babies for 10 minutes; Still: mothers will be asked to remain still while maintaining an unresponsive expressionless face and not to smile, touch, or talk to the child for 2 minutes (Still#1: 2 minutes; Still#2: 2 minutes); Reunion: mothers will be asked to resume the play activity with their own for an additional 2 minutes (Reunion#1: 2 minutes; Reunion#2: 2 minutes). | Diagnostic test | Typical developed children (TD), children with ND |
Primary outcome
Infant DNA methylation status
Time frame: 1 day , at the recruitment
The DNA methylation status (i.e. percentage) of candidate genes (e.g., OXTR, SLC6A4, BDNF, and DRD4) will be assessed from salivary samples obtained from infants.
Infant behavioral regulation
Time frame: 1 day , at the recruitment
The infant behavioral regulation (i.e., negative emotionality) will be coded micro-analitically (i.e., second-by-second) from videotapes of mother-infant interactions.
1 secondary outcome
Infant proteomic patterns
Time frame: 1 day , at the recruitment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2023.
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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.
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 Neurodevelopmental Disabilities and Emotional Regulation, run by IRCCS Eugenio Medea at 1 site in Italy.
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 14 inclusion and 0 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 18 Oct 2023. 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 Italy. 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 Rosario Montirosso (+39031877494, rosario.montirosso@lanostrafamiglia.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Infant DNA methylation status (time frame: 1 day , at the recruitment). 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 18 Oct 2023.