Trial to Improve Multisensory Neural Processing, Language & Motor Outcomes in Preterm Infants

• ClinicalTrials.gov Identifier: NCT03232931
• Recruitment Status: Active, not recruiting
• First Posted: July 28, 2017
• Results First Posted: March 19, 2024
• Last Update Posted: March 19, 2024
• Sponsor: Emory University
• Collaborators: National Institutes of Health (NIH); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Nationwide Children's Hospital
• Information provided by (Responsible Party): Nathalie Maitre, Emory University

Tracking Information

• First Submitted Date: February 3, 2017
• First Posted Date: July 28, 2017
• Results First Submitted Date: February 19, 2024
• Results First Posted Date: March 19, 2024
• Last Update Posted Date: March 19, 2024
• Actual Study Start Date: October 29, 2018
• Actual Primary Completion Date: February 20, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 19, 2024)

Index of Multisensory Processing (IMP) [ Time Frame: At enrollment up to 36 weeks gestation (prior to intervention), and at intervention completion up to 42 weeks gestation ]

Cortical processing is measured as the percentage of time spent in Event Related Potential (ERP) response patterns that have been previously characterized as typical in healthy infants born at full term. ERP is assessed through high-density functional electroencephalogram (EEG) in the NICU. The Index of Multisensory Processing (IMP) is calculated as the percentage of time that the topographical pattern of the participant's ERP to multisensory stimuli is most like template map of a full term infant. The IMP is expressed as a percentage from 100% (samples show nearly-typical activation all of the time) to 0% (samples show nearly-typical activation none of the time).

Original Primary Outcome Measures (submitted: July 25, 2017)

Latency of response to an audio and tactile stimuli on EEG/ERP [ Time Frame: at enrollment up to 36 weeks gestation and at intervention completion up to 42 weeks gestation ]

Change from baseline event related potential multisensory response at term-equivalent age (up to 42 weeks gestation)

Current Secondary Outcome Measures (submitted: February 19, 2024)

• Infant/Toddler Sensory Profile (ITSP) Score [ Time Frame: at 12 months corrected age ]
  The Infant/Toddler Sensory Profile (ITSP), for ages 7 to 36 months, is a 48-item questionnaire, completed by caregivers, and is used to measure sensory reactivity and adaptation to the environment. The ITSP assesses five sensory processing sections (Auditory, Visual, Tactile, Vestibular, and Oral Sensory Processing) and a General measure. Responses are given on a 5-point scale where 1 = almost always and 5 = almost never. For children 7 to 36 months there are four quadrant scores and one combined quadrant score available. For children 12 months corrected age, the four quadrant score ranges are as follows: Low Registration: 11-55 (typical performance is 46-54) Sensation Seeking: 14-70 (typical performance is 19-35) Sensory Sensitivity: 11-55 (typical performance is 41-52) Sensation Avoiding: 12-60 (typical performance is 45-56) Low Threshold (combined quadrant score): 23-115 (typical performance is 87-107)
• Change in Bayley Scales of Infant and Toddler Development - 3rd Edition (Bayley III) Score [ Time Frame: 12 and 24 months corrected age ]
  The Bayley-III is a standardized comprehensive assessment tool for assessing child development in children one month to 42 months old. The highest possible scaled score on each subtest is 19, and the lowest possible score is 1. Scores from 8 to 12 are considered average. Composite scores for motor and language domains are derived from sums of the subtest scaled scores. Composite scores range from 40-160.
• Change in Preschool Language Scales - 5th Edition (PLS-5) Score [ Time Frame: 2 Years (22-26 months corrected age) ]
  The PLS-5 is a language assessment tool administered by a trained professional in which children point or verbally respond to pictures or objects. It assesses both receptive (auditory comprehension) and expressive language skills in young children, and a total language score is also calculated. Total scores for Auditory Comprehension, Expressive Communication, and Total Language are standardized with a mean of 100 and a standard deviation of 15. Scores below 100 indicate below average performance while scores above 100 indicate better than average performance.

Original Secondary Outcome Measures (submitted: July 25, 2017)

• Infant/Toddler Sensory Profile [ Time Frame: at 12 months corrected age ]
  Sensory reactivity and adaptation to the environment: Infant/Toddler Sensory Profile Assessment
• Motor and language scores on Bailey III [ Time Frame: at 24 months corrected age ]
  Bailey III standard assessment

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Trial to Improve Multisensory Neural Processing, Language & Motor Outcomes in Preterm Infants
• Official Title: Randomized Controlled Trial to Improve Multisensory Neural Processing, Language & Motor Outcomes in Preterm Infants
• Brief Summary: Every year, almost all of ½ million infants born prematurely in the US and 15 million worldwide suffer from abnormal brain maturation resulting from interactions between immaturity and atypical sensory experiences after birth. This study uses rigorous scientific methods to measure the effects and determine the mechanisms of action of a parent-supported multisensory neurorehabilitative intervention for preterm infants, adaptable to a wide variety of neonatal environments, even when parents cannot be at their child's bedside. The intervention aims to improve brain multisensory processing, reactions to sensory stimulation in the home and long term language and motor development.

Detailed Description

This study is a randomized controlled trial design with intent-to-treat analysis in hospitalized preterm infants between 32 and 36 weeks post-menstrual age. Both the control and intervention groups will receive routine neonatal intensive care unit care (i.e., skin-to-skin care by parent when available and daily sessions of exposure to recorded parent's voice). In addition to routine care, the parent-supported multisensory intervention consists of sessions of standardized, therapist-administered, auditory-tactile stimulation that combines contingent recorded mother's voice delivered using a pacifier-activated system, during holding with supportive tactile containment against the therapist's chest, covered by cloth imprinted with mother's scent. Possible covariates, multi- and uni-sensory processing, will be measured at entry into the study and immediately after the treatment phase. Event-related potential (ERP) testing will be performed prior to the prior to intervention and after intervention is complete, which occurs at 36 weeks postmenstrual age (PMA) on average. ERP testing will take approximately 30 to 40 minutes. All infants will be seen at the neonatal intensive care unit (NICU) Follow-Up Program clinics at 9-12 months PMA (Year 1) and 22-24 months PMA (Year 2), where neurodevelopmental outcomes will be assessed using standardized methods.

Parents will also have the opportunity to consent separately to a secondary part to the study in which their infant would participate in one additional ERP testing session in the NICU between 34-36 weeks PMA and one additional visit to the clinical laboratory for ERP testing between 3-4 months PMA. This optional, secondary part of the study is observational only and does not influence randomization for the main trial. For the secondary part of the study, the population will be 40 of the 230 participants. All parents who are approached for the study prospectively and are randomized to control group will be asked if they would like to participate in the secondary part. Enrollment for this secondary part of the study will stop when 40 participants are reached.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

A randomized controlled trial design with intent-to-treat analysis in hospitalized preterm infants between 32 and 36 weeks post-menstrual age. Both the control and intervention groups will receive routine neonatal intensive care protocols (including skin-to-skin care by parent when available and daily sessions of exposure to recorded parent's voice). In addition to routine care, the parent-supported multisensory intervention consists of 10 sessions of standardized, therapist-administered, auditory-tactile stimulation that combines contingent recorded mother's voice delivered using a pacifier-activated system, during holding with supportive tactile containment against the therapist's chest, covered by cloth imprinted with mother's scent. Possible covariates, multi- and uni- sensory processing, will be measured at entry into the study and immediately after the treatment phase. Sensory reactivity will be measured at 1 year and language and motor outcomes will be assessed at 2 years.

Masking: Single (Outcomes Assessor)
Masking Description:

Except for parent reports, all measures will be administered by masked examiners.

Primary Purpose: Treatment

• Condition: Preterm Infant

Intervention

• Behavioral: Therapist skin-to-skin Care
  Skin-to-skin (STS) holding is part of the multisensory intervention where the therapist will wear a clean 100% cotton T-shirt with a clean hospital gown on top of the shirt and wrap the "kangaroo" positioner securely over the gown. A gauze square scented with parent's skin will be used to provide olfactory stimulation. Therapist STS sessions occur with simultaneous playing of mother's voice contingent on infant pacifier sucking.
• Device: Contingent parent's voice exposure
  The Pacifier Activated Lullaby® (PAL®) device, is a digital music delivery system that integrates a sensor, a pacifier routinely used in the NICU, and a receiver. It delivers a predetermined 10 seconds of recorded parent's voice singing lullabies upon detection of a suck that meets a preset pressure threshold. The original systems were modified for research use by decreasing the lower limit of activation thresholds for delivering the recording. Minimal effort is required to trigger the device. However, the settings ensure that regular attempts are needed to continue to receive continual presentation of the recording of mother's voice by requiring another suck after 10 seconds. The auditory stimulation with PAL will be provided when the infants are still awake (i.e., at the beginning of the session).
  Other Name: Pacifier Activated Lullaby® (PAL®)
• Behavioral: Parental skin-to-skin care
  The standard of care includes parental skin-to-skin care and exposure to parent's voice. During parental skin-to-skin care, infants are placed in a prone position with head positioned over the sternum, allowing transmission of breath and heart sounds to the developing ear. Deeper pressure is applied to offer support and feedback to the child's bottom. Session length is set to a minimum of 45 minutes per unit protocols.
• Device: Recorded parent's voice
  Per standard of care, preterm infants in the NICU currently receive noncontingent recorded parents' voice during two 20 minute sessions per day. Recordings are standardized and are played through a sterilizable device (DINO-egg).
  Other Name: DINO-egg

Study Arms

• Experimental: Multisensory Intervention
  Preterm infants in the NICU who are randomized to receive a multisensory intervention, in addition to the standard of care. The multisensory intervention uses recordings of the parents' voices and nurturing touch administered in the NICU during 12 to 23 sessions of standardized, therapist-administered, auditory-tactile stimulation, dispersed over a 2 to 3 week period. The intervention includes 2 components: (1) holding and light pressure containment of the infant against the hospital-gown covered chest of the therapist for tactile and non-specific auditory stimulation simultaneous with (2) playing of mother's voice contingent on infant pacifier sucking. Additionally, a gauze square scented with parent's skin will be used to provide olfactory stimulation.
  Interventions:

  • Behavioral: Therapist skin-to-skin Care
  • Device: Contingent parent's voice exposure
  • Behavioral: Parental skin-to-skin care
  • Device: Recorded parent's voice
• Standard of Care
  Preterm infants in the NICU who are randomized to receive the standard of care. The standard care for preterm infants in the NICU currently follows medical protocols of skin-to-skin holding and exposure to recordings of parent's voice.
  Interventions:

  • Behavioral: Parental skin-to-skin care
  • Device: Recorded parent's voice

Publications *

• Richard C, Jeanvoine A, Stark AR, Hague K, Kjeldsen C, Maitre NL. Randomized Trial to Increase Speech Sound Differentiation in Infants Born Preterm. J Pediatr. 2022 Feb;241:103-108.e3. doi: 10.1016/j.jpeds.2021.10.035. Epub 2021 Oct 25.
• Neel ML, Yoder P, Matusz PJ, Murray MM, Miller A, Burkhardt S, Emery L, Hague K, Pennington C, Purnell J, Lightfoot M, Maitre NL. Randomized controlled trial protocol to improve multisensory neural processing, language and motor outcomes in preterm infants. BMC Pediatr. 2019 Mar 19;19(1):81. doi: 10.1186/s12887-019-1455-1.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 19, 2024): 248
• Original Estimated Enrollment (submitted: July 25, 2017): 200
• Estimated Study Completion Date: March 2025
• Actual Primary Completion Date: February 20, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Hospitalization at a study location
• Postmenstrual age of 32 weeks 0 days gestation to 36 weeks 0 days gestation

Exclusion Criteria:

• Ventilation using an endotracheal tube
• Major congenital malformations
• Family history of genetic hearing loss
• Use of sedatives or seizure medications

Secondary Study Inclusion Criteria:

• Enrolled in the control group of the main study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 32 Weeks to 36 Weeks (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03232931
• Other Study ID Numbers: STUDY00003034; R01HD093706 ( U.S. NIH Grant/Contract ); IRB17-00025/IRB18-00579 ( Other Identifier: Nationwide Children's Hospital )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Nathalie Maitre, Emory University
• Original Responsible Party: Nathalie Maitre, Nationwide Children's Hospital, Associate Professor and Principal Investigator
• Current Study Sponsor: Emory University
• Original Study Sponsor: Nationwide Children's Hospital

Collaborators

• National Institutes of Health (NIH)
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Nationwide Children's Hospital

Investigators

• Principal Investigator: Nathalie L Maitre, MD, PhD; Emory University

• PRS Account: Emory University
• Verification Date: February 2024