Sleep Spindles Organization as an Early Neural Marker of Neuromotor Outcome

• Conditions: SMA1; Motor Outcome; Cerebral Palsy; EEG Sleep Spindles

• Registration Number: NCT06256887
• Lead Sponsor: IRCCS Fondazione Stella Maris

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-11-30
• Status Verified: 2024-02
• Study First Submitted: 2024-02-05
• Study First Submitted QC: 2024-02-05
• Last Update Submitted: 2024-02-05
• Study First Posted: 2024-02-13
• Last Update Posted: 2024-02-13
• Primary Completion: 2026-02
• Study Completion: 2026-04

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 80

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.

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Sleep EEG (T1,T2) - quantitative sleep spindles analysis	2-5 months, 12 (+/- 1) months	Primary predictive measure of the study
Clinical dichotomous outcome	18 (+/- 3) months	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).

Secondary Outcome Measures

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

Trial Locations

Locations (3)

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico; 🇮🇹 Milan, MI, Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS; 🇮🇹 Roma, Italy

IRCCS Fondazione Stella Maris; 🇮🇹 Calambrone, PI, Italy