Clinical trial NCT06256887: Sleep Spindles Organization as an Early Neural Marker of Neuromotor Outcome
Official title: 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.
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: EEG Sleep Spindles
Motor Outcome
Cerebral Palsy
SMA1
Keywords: Infant
Sensorimotor Development
Automatic spindle detector
Biomarker
EEG
Lead sponsor: IRCCS Fondazione Stella Maris
Sponsor class: OTHER
Collaborators: name: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
name: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
First posted: 2024-02-13
Enrollment: 80
Sex: ALL
Minimum age (years): 2
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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)

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Clinical dichotomous outcome
timeFrame: 18 (+/- 3) months
measure: Sleep EEG (T1,T2) - quantitative sleep spindles analysis
timeFrame: 2-5 months, 12 (+/- 1) months
Secondary outcomes:
measure: General Movements Assessment (GMA; T1)
timeFrame: 2-5 months
measure: Peabody Developmental Motor Scale (PDMS-II; T2 and T3)
timeFrame: 12 (+/- 1) months, 18 (+/- 3) months
measure: Hammersmith Infant Neurological Examination (HINE; T1, T2 and T3)
timeFrame: 2-5 months, 12 (+/- 1) months, 18 (+/- 3) months
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
state: MI
city: Calambrone
country: Italy
facility: IRCCS Fondazione Stella Maris
state: PI
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study officials:
affiliation: IRCCS Fondazione Stella Maris
name: Viviana Marchi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.