Background: Early prodromal signs of Autism Spectrum Disorder (ASD) can be detected within the first year of life, a period of heightened neuroplasticity. Pre-emptive, parent-mediated interventions delivered during this window may improve developmental outcomes and reduce ASD symptom severity, but evidence from adequately powered randomized trials in Europe remains limited. Early prodromal signs of Autism Spectrum Disorder (ASD) can be detected within the first year of life, a period of heightened neuroplasticity. Pre-emptive, parent-mediated interventions delivered during this window may improve developmental outcomes and reduce ASD symptom severity, but evidence from adequately powered randomized trials in Europe remains limited. Objectives: The primary objective of this trial is to determine the efficacy of FIRRST (Fostering Infant Responsivity and Reciprocity - Support to Thrive), a parent-mediated pre-emptive telehealth intervention, in reducing ASD symptom severity in infants with ASD prodromes, as measured by change in Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) Calibrated Severity Scores. Secondary objectives are to evaluate effects on infant developmental skills, caregiver-child interaction, parental well-being, neurophysiological markers, and cost-effectiveness. Methods: This is a multicenter, single-blinded, randomized, parallel-group superiority trial conducted in Italy. A total of 132 infants aged 9-14 months with ASD prodromes will be recruited by clinicians at participating university hospital-based centers and randomly allocated (1:1) to FIRRST or a Parent Education control condition. Key inclusion criteria include risk-range scores on the Social Attention and Communication Surveillance-Revised (SACS-R); exclusion criteria include known genetic, neurological, or severe sensory impairments. Randomization will be stratified by age (< 12 vs ≥ 12 months), sex, and ASD symptom severity. FIRRST consists of weekly telehealth sessions delivered by trained licensed health professionals over 24 weeks. Outcomes will be assessed at baseline, post-intervention (24 weeks), and follow-up (48 weeks). Outcomes: The primary outcome is change in ADOS-2 Calibrated Severity Scores from baseline to post-intervention. Secondary outcomes include developmental level (Griffiths-III), caregiver-child interaction (MONSI-CC), parental well-being (PSI-4), and neurophysiological measures derived from high-density electroencephalography. Safety outcomes include monitoring and descriptive reporting of adverse events. A cost-effectiveness analysis will be conducted from the healthcare system perspective. Trial registration: ClinicalTrials.gov NCT06817746. Registered on November 2024.
Fostering Infant Responsivity and Reciprocity – Support to Thrive (FIRRST): a multisite randomized control trial of a pre-emptive telehealth intervention for infants with early signs of Autism Spectrum Disorders in Italy
Calderoni, Sara;Conti, Eugenia;Guzzetta, Andrea
2026-01-01
Abstract
Background: Early prodromal signs of Autism Spectrum Disorder (ASD) can be detected within the first year of life, a period of heightened neuroplasticity. Pre-emptive, parent-mediated interventions delivered during this window may improve developmental outcomes and reduce ASD symptom severity, but evidence from adequately powered randomized trials in Europe remains limited. Early prodromal signs of Autism Spectrum Disorder (ASD) can be detected within the first year of life, a period of heightened neuroplasticity. Pre-emptive, parent-mediated interventions delivered during this window may improve developmental outcomes and reduce ASD symptom severity, but evidence from adequately powered randomized trials in Europe remains limited. Objectives: The primary objective of this trial is to determine the efficacy of FIRRST (Fostering Infant Responsivity and Reciprocity - Support to Thrive), a parent-mediated pre-emptive telehealth intervention, in reducing ASD symptom severity in infants with ASD prodromes, as measured by change in Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) Calibrated Severity Scores. Secondary objectives are to evaluate effects on infant developmental skills, caregiver-child interaction, parental well-being, neurophysiological markers, and cost-effectiveness. Methods: This is a multicenter, single-blinded, randomized, parallel-group superiority trial conducted in Italy. A total of 132 infants aged 9-14 months with ASD prodromes will be recruited by clinicians at participating university hospital-based centers and randomly allocated (1:1) to FIRRST or a Parent Education control condition. Key inclusion criteria include risk-range scores on the Social Attention and Communication Surveillance-Revised (SACS-R); exclusion criteria include known genetic, neurological, or severe sensory impairments. Randomization will be stratified by age (< 12 vs ≥ 12 months), sex, and ASD symptom severity. FIRRST consists of weekly telehealth sessions delivered by trained licensed health professionals over 24 weeks. Outcomes will be assessed at baseline, post-intervention (24 weeks), and follow-up (48 weeks). Outcomes: The primary outcome is change in ADOS-2 Calibrated Severity Scores from baseline to post-intervention. Secondary outcomes include developmental level (Griffiths-III), caregiver-child interaction (MONSI-CC), parental well-being (PSI-4), and neurophysiological measures derived from high-density electroencephalography. Safety outcomes include monitoring and descriptive reporting of adverse events. A cost-effectiveness analysis will be conducted from the healthcare system perspective. Trial registration: ClinicalTrials.gov NCT06817746. Registered on November 2024.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
