Creating a Calmer NICU: Optimizing Growth and Brain Development in Preterm Infants

NCT ID: NCT04911452

Last Updated: 2025-01-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-27
• Study Completion Date: 2025-12-31

Brief Summary

Infants born preterm can spend months in the neonatal intensive care unit (NICU) where they experience stressful but essential procedures. Untreated stress is associated with altered brain development. Skin-to-skin care (SSC) is one of the most effective behavioral strategies for mitigating preterm infant stress and improving brain maturation. However, parents may not be always available to provide SSC; some infants cannot be held for long periods for medical reasons. To address this problem, investigators designed Calmer, a patented, prototype therapy bed, for reducing stress in preterm infants. Calmer fits into NICU incubators and provides simultaneously an artificial skin surface, heartbeat sounds and breathing motion, mimicking aspects of SSC; the latter 2 features are individualized for each infant based on their parents' recordings. The 1st randomized controlled trial (RCT) in 58 preterm babies showed that during a routine blood test: Calmer lowered infant behavioral and heart stress responses and stabilized brain blood flow no differently than facilitated tucking; infants could be cared for safely on Calmer up to 6 hours in 1 day; Calmer was well accepted by mothers and staff.

The goal now is to determine the efficacy of Calmer use over 3 weeks to support optimal physical growth and brain development in preterm infants. A 2-group (treatment, control) pilot RCT to test the implementation of an increased "dose" of Calmer exposure over 2-3 continuous weeks is proposed. 30 infants born between 26-30 weeks gestational age in the NICU will be randomized to receive either Calmer, for a minimum of 3 hours in total/day for 2-3 continuous weeks, or to 2-3 weeks of standard NICU care (minimum of 2 and maximum of 3 weeks).

Research questions:

Trial feasibility Q1. Is it feasible to enrol 30 infants, complete a 2-3-week treatment period (minimum of 2 and maximum of 3 weeks), and measure growth outcomes in preterm infants (26-30 weeks GA) in the NICU in a pilot RCT of daily Calmer treatment versus standard NICU care to inform a larger, definitive RCT?

Infant outcomes Q2a. Are there differences in physical growth markers (daily weight gain, head circumference, body length) between preterm infants who receive Calmer and those who receive standard NICU care measured before (baseline) and after 2-3 weeks of daily Calmer exposure? Q2b. Are there differences in brain activity markers, as measured by cerebral electrical (EEG) signalling, between preterm infants who receive Calmer and those who receive standard NICU care, measured during a resting/sleeping state and routine diaper change session at the end of the trial (post 2-3 weeks of daily Calmer exposure)?

Detailed Description

Pilot trial implementation targets:

Targets for success would be that the informed consent rate will be at least 40%, 30 patients will be enrolled in 48 months, 95% of infants will receive the 3 hour minimum treatment, and patient assessment completion rate will be at least 85%.

The results of this pilot trial will be used to inform the design of a larger RCT. The results of this pilot trial will allow to assess patient accrual, protocol adherence, and to monitor the completeness and quality of the outcome data. If implementation targets are met, an application for further funding to use this protocol in a larger, multisite, non-inferiority trial comparing SSC + Calmer to SSC alone will be put forth.

Conditions

Prematurity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Control

Standard Neonatal Intensive Care Unit (NICU) care

Group Type: NO_INTERVENTION

No interventions assigned to this group

Calmer

Calmer placed and left in infant incubator for a minimum of 2 and maximum of 3 weeks.

Calmer treatment provided for minimum total of 3 hours/day (can be discontinuous).

Group Type: EXPERIMENTAL

Calmer

Intervention Type: DEVICE

Once randomized, infants in the Calmer group will receive treatment for a minimum cumulative total of 3 hours/day during periods when the infant may be too ill to be held or when parents do not wish to hold their infant or are not present. Calmer does not replicate a parent's contact and so the minimum exposure has been tripled. No upper limit of Calmer use will be set. Each day, the research and/or bedside nurse will record the heart and respiratory rates for a two-minute period. The one-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 Neonatal Intensive Care Unit (NICU) research nurse will also train the parents/caregivers to self-measure their resting heart and breathing rates so that if they are away from the NICU for more than one day, these values can be sent to the research/ bedside nurse by phone.

Interventions

Calmer

Once randomized, infants in the Calmer group will receive treatment for a minimum cumulative total of 3 hours/day during periods when the infant may be too ill to be held or when parents do not wish to hold their infant or are not present. Calmer does not replicate a parent's contact and so the minimum exposure has been tripled. No upper limit of Calmer use will be set. Each day, the research and/or bedside nurse will record the heart and respiratory rates for a two-minute period. The one-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 Neonatal Intensive Care Unit (NICU) research nurse will also train the parents/caregivers to self-measure their resting heart and breathing rates so that if they are away from the NICU for more than one day, these values can be sent to the research/ bedside nurse by phone.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Preterm infants admitted to the neonatal intensive care unit (NICU) at the British Columbia (BC) Women's Hospital born at 26-30 completed weeks gestational age (GA). GA is determined accurately using early gestation ultrasonogram (standard of care in BC), or calculated using the last menstrual period;
• Infants who are on continuous positive airway pressure or are ventilated;
• At least one parent/caregiver must speak sufficient English to provide consent

Exclusion Criteria

• Infants who have congenital anomalies, small for GA (per medical admission history), or have a history of maternal abuse of controlled drugs and substances; - Infants with an ongoing infection at the time of enrolment;
• Infants that have pre-existing cardiovascular instability defined by shock/hypotension/need for cardiovascular drugs
• Infants receiving paralytic drugs;
• Infants that have major neurological injury (e.g. hypoxic ischemic encephalopathy, hemorrhage/stroke);
• Infants who are beyond the 30th completed week GA (30 weeks + 6 days) at enrolment.

• Minimum Eligible Age: 26 Weeks
• Maximum Eligible Age: 30 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Women's Health Research Institute of British Columbia

OTHER

Sponsor Role: collaborator

University of British Columbia

OTHER

Sponsor Role: lead

Responsible Party

Manon Ranger

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Liisa Holsti, PhD

Role: PRINCIPAL_INVESTIGATOR

The University of British Columbia

Manon Ranger, PhD

Role: PRINCIPAL_INVESTIGATOR

The University of British Columbia

Locations

British Columbia Women's Hospital and Health Centre

Vancouver, British Columbia, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Manon Ranger, PhD

Role: CONTACT

manon.ranger@ubc.ca

1-604-827-1382

Lindsay Richter, MSc

Role: CONTACT

lindsay.richter@cw.bc.ca

1-604-875-2000 ext. 7408

Facility Contacts

Manon Ranger, PhD

Role: primary

manon.ranger@ubc.ca

1-604-827-1382

Naama Rozen, MSc

Role: backup

Naama.Rozen@cw.bc.ca

1-604-875-2000 ext. 7408

References

Johnston C, Campbell-Yeo M, Disher T, Benoit B, Fernandes A, Streiner D, Inglis D, Zee R. Skin-to-skin care for procedural pain in neonates. Cochrane Database Syst Rev. 2017 Feb 16;2(2):CD008435. doi: 10.1002/14651858.CD008435.pub3.

Reference Type: BACKGROUND

PMID: 28205208 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31041426 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 33490850 (View on PubMed)

Williams N, MacLean K, Guan L, Collet JP, Holsti L. Pilot Testing a Robot for Reducing Pain in Hospitalized Preterm Infants. OTJR (Thorofare N J). 2019 Apr;39(2):108-115. doi: 10.1177/1539449218825436. Epub 2019 Feb 15.

Reference Type: BACKGROUND

PMID: 30770034 (View on PubMed)

Fenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr. 2013 Apr 20;13:59. doi: 10.1186/1471-2431-13-59.

Reference Type: BACKGROUND

PMID: 23601190 (View on PubMed)

Hauser S, Suto MJ, Holsti L, Ranger M, MacLean KE. Designing and Evaluating Calmer, a Device for Simulating Maternal Skin-to-Skin Holding for Premature Infants. In Proceedings of the 2020 CHI Conference on Human Factors in Computing Systems (CHI '20). 2020. Association for Computing Machinery, New York, NY, USA: 1-15. https://doi.org/10.1145/3313831.3376539

Reference Type: BACKGROUND

Other Identifiers

H21-00527

Identifier Type: -

Identifier Source: org_study_id