Sleep Spindles Organization as an Early Neural Marker of Neuromotor Outcome

NCT06256887 | Enrolling By Invitation

• 1 other identifier: GR-2021-12375367
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of this observational study is to test the effectiveness of quantitative early biomarkers in the sleep electroencephalogram (EEG), namely sleep spindles, as predictors of early sensorimotor maturation and long-term motor outcome. Spindles are discrete events, prominent over sensorimotor areas, that reflect motor learning overnight consolidation. They represent a potential marker for the investigation of altered early sensorimotor reorganization and long-term motor outcomes in the case of neuromotor pathologies. To test this hypothesis, we will validate the prognostic accuracy of a semi-automated EEG sleep-spindles analysis in two clinical populations: 1) infants with a perinatal brain lesion, at risk of Cerebral Palsy (CP), 2) infants with Spinal muscular atrophy type 1 (SMA1), a neuromuscular disease detectable at birth with variable response to early pharmacological treatment. A group of typically developing infants (at very low neurological risk) will be enrolled in the study as control group. All participants will undergo two sleep EEG recordings at 2-5 months (T1) and 12 months (T2), respectively. Short-term neuromotor outcome will be evaluated at T1 and T2, through standard and validated assessment. Long-term neuromotor development will be defined at 18 months (T3; i.e. CP vs NO CP; SMA treatment responders vs No responders). Primary clinical and motor outcomes will be used for estimating the effectiveness of spindles' features at T1 and T2 as predictors of later clinical and motor outcomes at T3. EEG sleep features will be considered both cross-sectionally, at each time point (T1, and T2), and from a longitudinal perspective. Differences in the EEG sleep-spindle features will be evaluated within- and between-groups.

Conditions

EEG Sleep Spindles; Motor Outcome; Cerebral Palsy; SMA1

Keywords

Infant; Sensorimotor Development; Automatic spindle detector; Biomarker; EEG

Outcome Measures

Primary Outcomes (2)

• Clinical dichotomous outcome

  For infants with perinatal brain damage, the primary outcome will be the diagnosis of CP: CP-YES vs CP-NO. For infants with SMA, the primary outcome will be the response to treatment: responders (SMA-R) vs non-responders (SMA-NR).

  18 (+/- 3) months

• Sleep EEG (T1,T2) - quantitative sleep spindles analysis

  Primary predictive measure of the study

  2-5 months, 12 (+/- 1) months

Secondary Outcomes (3)

• General Movements Assessment (GMA; T1)

  2-5 months

• Peabody Developmental Motor Scale (PDMS-II; T2 and T3)

  12 (+/- 1) months, 18 (+/- 3) months

• Hammersmith Infant Neurological Examination (HINE; T1, T2 and T3)

  2-5 months, 12 (+/- 1) months, 18 (+/- 3) months

Study Arms (3)

Infants at risk of Cerebral Palsy

N= 20, Infants at risk of Unilateral Cerebral Palsy (UCP); N= 20, Infants at risk of Bilateral Cerebral Palsy (BCP).

Infants with diagnosis of SMA1

N=20, Infants with a diagnosis of SMA type 1.

Infants at very low neurodevelopmental risk (control group)

N=20, Infants born preterm or at term in absence of perinatal neurological complications, therefore a very low neurodevelopmental risk.

Eligibility Criteria

• Age: 2 Months - 5 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

* Infants at risk of Cerebral Palsy * Infants with diagnosis of SMA type 1 * Infants at very low neurodevelopmental risk (control group)

You may qualify if:

• Infants aged 0-5 months who are at high-risk of Cerebral Palsy (CP): preterm and at term infants with a documented pre- or perinatal brain lesion at the neonatal brain MRI (i.e. hypoxic-ischemic brain injury, ischemic or hemorrhagic stroke, cystic periventricular leukomalacia, periventricular hemorrhagic infarction associated with germinal matrix-intraventricular haemorrhage);
• Infant aged 0-5 months who have received the diagnosis of SMA1, according to the perinatal genetic screening, and undergo early pharmacological treatment;
• Infants aged 0-5 months at very low neurodevelopmental risk (Control group): infants born preterm or at term in absence of perinatal neurological complications.

You may not qualify if:

• Presence of drug-resistant epilepsy or active epilepsy at T1,
• Severe sensory deficits (blindness or deafness)
• Diagnosis of progressive neurological disorders, other than SMA.

Sponsors & Collaborators

• IRCCS Fondazione Stella Maris: lead
• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: collaborator
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: collaborator

Study Sites (3)

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Milan, MI, Italy

Location

IRCCS Fondazione Stella Maris

Calambrone, PI, 56128, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, Italy

Location

Related Publications (1)

• Marchi V, Rizzi R, Nevalainen P, Melani F, Lori S, Antonelli C, Vanhatalo S, Guzzetta A. Asymmetry in sleep spindles and motor outcome in infants with unilateral brain injury. Dev Med Child Neurol. 2022 Nov;64(11):1375-1382. doi: 10.1111/dmcn.15244. Epub 2022 Apr 20.

  PMID: 35445398 BACKGROUND

MeSH Terms

Conditions

Cerebral Palsy

Condition Hierarchy (Ancestors)

Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Viviana Marchi, MD, PhD

  IRCCS Fondazione Stella Maris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: February 5, 2024
• First Posted: February 13, 2024
• Study Start: November 30, 2023
• Primary Completion: February 1, 2026
• Study Completion: April 1, 2026
• Last Updated: February 13, 2024

Record last verified: 2024-02

Locations

IT (3)