Sleep Spindles Organization as an Early Neural Marker of Neuromotor Outcome (SONNO)

SONNO - Sleep Spindles Organization as an Early Neural Marker of Neuromotor Outcome: a New, Fast, Safe, Cost-effective and Infant-friendly EEG Tool to Monitor Early Sensory-motor Function in Infants at Risk of Neuromotor Disorders.

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Cerebral Palsy; Motor Outcome; SMA1; EEG Sleep Spindles

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

Study Locations

• Italy
  • Roma, Italy
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  • MI
    • Milan, MI, Italy
      • Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
  • PI
    • Calambrone, PI, Italy, 56128
      • IRCCS Fondazione Stella Maris

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

• 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)

Description

Inclusion Criteria:

• 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.

Exclusion Criteria (apply all groups):

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
General Movements Assessment (GMA; T1)	Short-term motor outcome	2-5 months
Peabody Developmental Motor Scale (PDMS-II; T2 and T3)	Long-term motor outcome	12 (+/- 1) months, 18 (+/- 3) months
Hammersmith Infant Neurological Examination (HINE; T1, T2 and T3)	Clinical short- and long-term outcome	2-5 months, 12 (+/- 1) months, 18 (+/- 3) months

Collaborators and Investigators

• Sponsor: IRCCS Fondazione Stella Maris
• Collaborators: Fondazione Policlinico Universitario Agostino Gemelli IRCCS; Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
• Investigators: Principal Investigator: Viviana Marchi, MD, PhD, IRCCS Fondazione Stella Maris

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2023
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: February 5, 2024
• First Submitted That Met QC Criteria: February 5, 2024
• First Posted (Actual): February 13, 2024

Study Record Updates

• Last Update Posted (Actual): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Biomarker; Infant; EEG; Sensorimotor Development; Automatic spindle detector
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Damage, Chronic; Cerebral Palsy
• Other Study ID Numbers: GR-2021-12375367

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No