NCT04617587

Brief Summary

Preterms are early exposed to a stressful environment (i.e. excessive sensory stimulation and paucity of parental contact) with subsequent detrimental effects on brain maturation and neurodevelopmental outcomes. In contrast, early interventions seem to reduce stress exposure and promote neurodevelopment. The brain functional plasticity in response to environmental experiences can be partly attributed to changes in DNA methylation. In this context, LINE-1 (L1) promoter (18% of human genome) methylation/demethylation has been associated with L1 somatic mobilization in the brain genomes, contributing to experience-driven brain plasticity; this mechanism being deregulated in important neurological disease. This study aims at identifying and characterizing the role of L1 DNA repeats as a novel biomarker to predict long-term neurodevelopmental outcome in preterm infants. In addition, the study's secondary goal will be to define a preventive approach, based on early intervention strategies, for improving long-term neurodevelopmental outcomes.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
104

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Dec 2020

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 23, 2020

Completed
13 days until next milestone

First Posted

Study publicly available on registry

November 5, 2020

Completed
28 days until next milestone

Study Start

First participant enrolled

December 3, 2020

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 21, 2025

Completed
9 days until next milestone

Study Completion

Last participant's last visit for all outcomes

March 30, 2025

Completed
Last Updated

May 1, 2025

Status Verified

April 1, 2025

Enrollment Period

4.3 years

First QC Date

October 23, 2020

Last Update Submit

April 30, 2025

Conditions

Premature Birth

Keywords

Premature BirthDNA MethylationL1 ElementsEpigenometicsEarly InterventionBrain DevelopmentNeurodevelopmentParent-infant interactionMassage therapyVisual interaction

Outcome Measures

Primary Outcomes (1)

  • L1 Promoter Methylation Levels on Biological Materials

    Epigenetic analysis is performed on biological materials: cord blood sample and buccal swab at birth, peripheral blood sample and buccal swab at NICU discharge/term equivalent age, buccal swab collected during the follow up assessment at 12 and 24 months of corrected age.

    Up to 24 months corrected age

Secondary Outcomes (6)

  • Conventional and advanced brain Magnetic Resonance Imaging (MRI)

    Term equivalent age, approximately 40 weeks postmenstrual age

  • Neurological Examination

    Term equivalent age, approximately 40 weeks postmenstrual age

  • General Movements Examination

    Term equivalent age, approximately 40 weeks postmenstrual age

  • Visual Assessment

    Term equivalent age, approximately 40 weeks postmenstrual age

  • Neurodevelopmental Outcome

    Up to 24 months corrected age

  • +1 more secondary outcomes

Study Arms (1)

Early Intervention

EXPERIMENTAL

All the enrolled preterm infants are assigned to receive the early neurodevelopmental intervention during the NICU stay.

Behavioral: Early Intervention

Interventions

Early InterventionBEHAVIORAL

The early intervention (EI) is delivered during the NICU stay. It is a multisensory intervention which consists in three parts: parental training, massage therapy and visual interaction. The EI is first focused on parental training, according to PremieStart Protocol, in order to train parents to: recognize signs of infant stress and alert-available behavior through the identification of infant's behavioral states; adopt principles of graded stimulation; sustain infant's attention and respond to infant's cues; optimize interactions and avoid overwhelming infants through facilitation strategies. The program is held in eight main sessions and one additional post-discharge session. In addition, parents are trained and invited to daily promote preterm baby massage therapy and visual interaction (visual fixation/tracking and visual attention).

Early Intervention

Eligibility Criteria

Age24 Weeks - 32 Weeks
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Gestational age at birth between 24+0 and 32+6 weeks
  • Mothers age over 18 years
  • Good comprehension of the Italian language
  • Written informed consent signed by both parents

You may not qualify if:

  • Infants with major genetic disorders and malformations
  • Parents declined study participation
  • Single-parent family
  • Parents with obvious cognitive or psychiatric disorders and drug addiction

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

NICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Related Publications (5)

  • Fontana C, De Carli A, Ricci D, Dessimone F, Passera S, Pesenti N, Bonzini M, Bassi L, Squarcina L, Cinnante C, Mosca F, Fumagalli M. Effects of Early Intervention on Visual Function in Preterm Infants: A Randomized Controlled Trial. Front Pediatr. 2020 Jun 4;8:291. doi: 10.3389/fped.2020.00291. eCollection 2020.

    PMID: 32582595BACKGROUND

  • Newnham CA, Milgrom J, Skouteris H. Effectiveness of a modified Mother-Infant Transaction Program on outcomes for preterm infants from 3 to 24 months of age. Infant Behav Dev. 2009 Jan;32(1):17-26. doi: 10.1016/j.infbeh.2008.09.004. Epub 2008 Nov 20.

    PMID: 19026450BACKGROUND

  • Bedrosian TA, Quayle C, Novaresi N, Gage FH. Early life experience drives structural variation of neural genomes in mice. Science. 2018 Mar 23;359(6382):1395-1399. doi: 10.1126/science.aah3378.

    PMID: 29567711BACKGROUND

  • Ricci D, Romeo DM, Serrao F, Cesarini L, Gallini F, Cota F, Leone D, Zuppa AA, Romagnoli C, Cowan F, Mercuri E. Application of a neonatal assessment of visual function in a population of low risk full-term newborn. Early Hum Dev. 2008 Apr;84(4):277-80. doi: 10.1016/j.earlhumdev.2007.10.002. Epub 2007 Nov 8.

    PMID: 17996405BACKGROUND

  • Guzzetta A, Baldini S, Bancale A, Baroncelli L, Ciucci F, Ghirri P, Putignano E, Sale A, Viegi A, Berardi N, Boldrini A, Cioni G, Maffei L. Massage accelerates brain development and the maturation of visual function. J Neurosci. 2009 May 6;29(18):6042-51. doi: 10.1523/JNEUROSCI.5548-08.2009.

    PMID: 19420271BACKGROUND

MeSH Terms

Conditions

Premature Birth

Interventions

Early Intervention, Educational

Condition Hierarchy (Ancestors)

Obstetric Labor, PrematureObstetric Labor ComplicationsPregnancy ComplicationsFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital Diseases

Intervention Hierarchy (Ancestors)

Child Health ServicesCommunity Health ServicesHealth ServicesHealth Care Facilities Workforce and ServicesPreventive Health Services

Study Officials

  • Monica Fumagalli, MD, PhD

    Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

    PRINCIPAL INVESTIGATOR

  • Beatrice Bodega, PhD

    Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 23, 2020

First Posted

November 5, 2020

Study Start

December 3, 2020

Primary Completion

March 21, 2025

Study Completion

March 30, 2025

Last Updated

May 1, 2025

Record last verified: 2025-04

Locations

IT(1)