Calmer Brains in Very Preterm Infants

NCT07262385 | Not Yet Recruiting

• 1 other identifier: H25-01015
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Very preterm infants in the neonatal intensive care unit (NICU) need lifesaving medical procedures which can be stressful and affect brain development. Calmer was invented to mimic key parts of parental holding (touch, heartbeat sounds and breathing motion) to help reduce stress if parents cannot be there to hold their infant. Using specialized brain scans done at full term, we will gather initial information in 22 infants born 3-4 months early to compare brain development in infants who receive Calmer at least 3 hours each day (+ regular NICU care) over 2-3 weeks with infants who have regular NICU care.

Conditions

Premature Infant

Keywords

Prematurity; Brain development; Stress; NICU; Pilot RCT; Feasibility; Calmer - therapeutic medical device

Outcome Measures

Primary Outcomes (3)

• Brain Volumes

  Anatomical analysis: Anatomical images (T2w) will be manually inspected for quality control. Images with very poor tissue contrast or motion artefacts will be rejected. T2w images will be bias-field corrected using ANTs N4ITK. The images will then be skull-stripped and segmented using the dHCP anatomical pipeline to calculate total and sub-regional brain volumes.

  When each participant reaches 40 weeks post-conceptual age and return for their MRI scan

• Brain Functional Connectivity

  Resting state fMRI analysis: Fieldmaps will be generated using the dual-echo EPI and magnitude scan. The dHCP functional pipeline will be implemented to achieve distortion-correction and motion-correction, register the functional image to the corresponding T2w structural image, generate a transform matrix from functional space to the 40-week T2w template; and we will perform temporal high-pass filtering (150 s high-pass cutoff) and independent component analysis (ICA) denoising using ICA FIX. Scans with a mean FD \> 1 mm will be excluded. The dHCP functional pipeline will then be run on all subjects using the study-specific training file. Spatial smoothing of 5 mm will be applied using FSL's SUSAN and grand mean intensity normalization will be computed. Functional connectivity measures will be computed using the CONN toolbox.

  When each participant reaches 40 weeks post-conceptual age

• Brain Fractional Anisotropy

  Diffusion tensor imaging analysis: The dHCP neonatal dMRI data processing pipeline will be used to pre-process the diffusion weighted images. Briefly, opposite phase b0 images are used to estimate the off-resonance field that is then used in the simultaneous correction of motion artefacts, susceptibility-induced and eddy current distortions. Data will then be super-resolved and, after pre-processing is complete, local diffusion and microstructural models are fitted in every voxel and averaged to calculate mean fractional anisotropy.

  When participants reach term-equivalent age

Secondary Outcomes (2)

• Clinical weight measures

  From the start of study treatment (or enrolment if Control group) to 2-3 weeks later, at the end of intervention exposure.

• Head growth measures

  From the start of study treatment (or enrolment if Control group) to 2-3 weeks later, at the end of intervention exposure.

Other Outcomes (4)

• Trial feasibility

  2 years from the start of the study

• Trial feasibility

  2 years from the start of the study

• Trial feasibility

  2 years from the start of the study

Study Arms (2)

Calmer

EXPERIMENTAL

Infants in the Calmer group will have a Calmer\* placed and left in their incubators for a minimum of 2 and maximum of 3 weeks and will receive treatment for a minimum cumulative total of 3 hours/day (i.e. time can be discontinuous). Each day, after the infant's parent rests for 10 minutes, the research and/or bedside nurse will record the heart and respiratory rates for a 2-minute period (or taken by the caregiver themselves after training by research/NICU staff). The 1-minute average will be used to program Calmer for each infant that day to better simulate day-to-day changes in infant-parent contact. The values can be adjusted over the day as parents wish. \*Calmer, a patented, therapeutic bed that mimics key aspects of skin-to-skin care (SSC) to reduce stress in preterm infants. Calmer fits into NICU incubators and delivers 3 key SSC stimuli: touch, breathing motion, and heartbeat sounds (rates individualized to each infant based on their parents' HR/RR).

Device: Calmer

Control

NO INTERVENTION

Infants in the Control group will receive standard NICU care, including parent SSC.

Interventions

Calmer DEVICE

Calmer, a unique, patented, therapeutic bed that mimics key aspects of SSC that reduce stress in preterm infants. Calmer fits into NICU incubators and cribs, and delivers 3 key SSC stimuli: touch, breathing motion, and heartbeat sounds; the rates of the latter 2 stimuli are individualized to each infant based on their parents' breathing and heart rates. Calmer is designed to provide complementary care only when parents are not able to give SSC. It is not meant nor designed to replace human SSC, so will never be tested as such a replacement. Instead, Calmer was invented to enhance and optimize brain development in preterm infants by reducing stress during the NICU stay, when parents/caregivers are not available for SSC. Our ultimate goal is to enable use of Calmer from an infant's admission to discharge, only during those times when caregivers are not available.

Calmer

Eligibility Criteria

• Age: 26 Weeks - 30 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Very preterm infants admitted to the NICU at the BC Women's Hospital

You may not qualify if:

• Congenital anomalies;
• Born small for GA (per medical admission history);
• History of birthing parent substance use in pregnancy;
• Ongoing infection at the time of enrollment;
• Pre-existing cardiovascular instability defined by shock/hypotension/need for cardiovascular drugs;
• Receiving paralytic drugs;
• Major neurological injury (e.g. hypoxic ischemic encephalopathy, hemorrhage/stroke; VP shunt);
• Beyond the 30th completed week GA (30 weeks + 6 days) at enrollment.

Sponsors & Collaborators

• BC Children's Hospital Research Institute: collaborator
• University of British Columbia: lead

Study Sites (1)

BC Women's Hospital & Health Centre

Vancouver, British Columbia, V6H 3N1, Canada

Location

Related Publications (2)

• Holsti L, MacLean K, Oberlander T, Synnes A, Brant R. Calmer: a robot for managing acute pain effectively in preterm infants in the neonatal intensive care unit. Pain Rep. 2019 Mar 14;4(2):e727. doi: 10.1097/PR9.0000000000000727. eCollection 2019 Mar-Apr.

  PMID: 31041426 RESULT

• Ranger M, Albert A, MacLean K, Holsti L. Cerebral hemodynamic response to a therapeutic bed for procedural pain management in preterm infants in the NICU: a randomized controlled trial. Pain Rep. 2021 Jan 12;6(1):e890. doi: 10.1097/PR9.0000000000000890. eCollection 2021 Jan-Feb.

  PMID: 33490850 RESULT

MeSH Terms

Conditions

Premature Birth

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Manon Ranger, PhD

  University of British Columbia

  PRINCIPAL INVESTIGATOR

• Liisa Holsti, PhD

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Manon Ranger, PhD

CONTACT

604-827-1382; manon.ranger@ubc.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: We will conduct a single-site, single-blind, two-group (treatment and control), randomized pilot trial and determine the feasibility of our study design. We will also gather preliminary data of Calmer's effect on infant structural and functional brain development to inform a larger trial.

Study Record Dates

• First Submitted: July 4, 2025
• First Posted: December 3, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: December 3, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR, ANALYTIC CODE
• Time Frame: When the research findings are published.
• Access Criteria: We have not decided on these details.

Locations

CA (1)