Clinical trial NCT04911452: Creating a Calmer NICU: Optimizing Growth and Brain Development in Preterm Infants
Official title: Creating a CALMER NICU: Pilot Testing a Robot for Optimizing Growth and Brain Development in Preterm Infants in the NICU
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Prematurity
Keywords: Prematurity
Neonatal intensive care
Growth
Robotic device
Skin-to-skin care
Stress
Brain activity
EEG
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: Women's Health Research Institute of British Columbia
First posted: 2021-06-03
Enrollment: 30
Sex: ALL
Minimum age (years): 26
Maximum age (years): 30
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single-site, single-blind, two-group (treatment and control), randomized pilot trial
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Trial feasibility: Consent rates
timeFrame: 48 months
measure: Trial feasibility: Protocol delivery rate
timeFrame: 48 months
measure: Trial feasibility: Complete outcome measures
timeFrame: 48 months
measure: Trial feasibility: Safety issues
timeFrame: 48 months
Secondary outcomes:
measure: Brain activity at rest and during stress event (routine diaper change)
timeFrame: 2-3 weeks
measure: Weight gain
timeFrame: 2-3 weeks
measure: Nutritional status
timeFrame: 2-3 weeks
measure: Head circumference
timeFrame: 2-3 weeks
measure: Body length
timeFrame: 2-3 weeks
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: British Columbia Women's Hospital and Health Centre
state: British Columbia
Study officials:
affiliation: The University of British Columbia
name: Liisa Holsti, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: The University of British Columbia
name: Manon Ranger, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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