Sleep Spindles Organization as an Early Neural Marker of Neuromotor Outcome

Cerebral Palsy Clinical Trial

— SONNO  

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.

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06256887
• Other study ID #: GR-2021-12375367
• Status: Enrolling by invitation
• Start date: November 30, 2023
• Est. completion date: April 2026

Study information

• Verified date: February 2024
• Source: IRCCS Fondazione Stella Maris
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 80
• Est. completion date: April 2026
• Est. primary completion date: February 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 2 Months to 5 Months

Eligibility

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.

Related Conditions & MeSH terms

• Cerebral Palsy

Locations

Country	Name	City	State
Italy	IRCCS Fondazione Stella Maris	Calambrone	PI
Italy	Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico	Milan	MI
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma

Sponsors (3)

Lead Sponsor	Collaborator
IRCCS Fondazione Stella Maris	Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Country where clinical trial is conducted

Italy, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Sleep EEG (T1,T2) - quantitative sleep spindles analysis	Primary predictive measure of the study	2-5 months, 12 (+/- 1) months
Secondary	General Movements Assessment (GMA; T1)	Short-term motor outcome	2-5 months
Secondary	Peabody Developmental Motor Scale (PDMS-II; T2 and T3)	Long-term motor outcome	12 (+/- 1) months, 18 (+/- 3) months
Secondary	Hammersmith Infant Neurological Examination (HINE; T1, T2 and T3)	Clinical short- and long-term outcome	2-5 months, 12 (+/- 1) months, 18 (+/- 3) months