Comparing the Side-lying Sleep Positioning to Back-lying in Infants With Cleft Palate (SLUMBRS2)

Comparing the Effectiveness of Side-lying Sleep Positioning to Back-lying at Reducing Oxygen Desaturation Resulting From Obstructive Sleep Apnoea in Infants With Cleft Palate

The craniofacial abnormalities found in infants and children with cleft palate (CP) lead to increased risk of obstructive sleep apnoea (OSA). In children and adults sleep position is known to influence the patency of the airway during sleep. Altering sleep position in infants with CP may offer a 'low-cost, high impact' intervention to limit the negative impacts of OSA on child development.

Children with CP are at increased risk of impairment in learning, memory and cognition, with OSA representing an additional risk to cognitive development. Infants with CP are at risk of poor weight gain and 'failure to thrive', which can be further exacerbated by co-existing OSA.

The design and conduct of the proposed randomised controlled trial will benefit from lessons learned from both the feasibility and other previous studies. Investigators demonstrated that existing advice given about sleep position varied significantly with some centres recommending back-lying and others side-lying. Sample size calculations were based on this multi-source data. Parents in the feasibility study knew that sleep position advice for infants with CP changes regularly. They understood why not adhering to 'national guidance' (DoH 2009, Back to Sleep) could be necessary as their infants are "different to normal infants".

How will this study benefit infants with cleft palate and their parents? The proposed study will eliminate the current uncertainty and variability in advice provided to parents of infants with CP, whilst potentially limiting the negative impact of OSA on development. This work has been prioritised and received unanimous support from Cleft Lip and Palate Association (CLAPA), Craniofacial Society Great Britain and Ireland (CFSGBI) and Clinical Nurse Specialists. Aim.To determine the clinical effectiveness in infants with CP of side-lying as compared to back-lying sleep positioning in reducing oxygen desaturation resulting from OSA.

Study Overview

• Status: Recruiting
• Conditions: Obstructive Sleep Apnea; Cleft Palate
• Intervention / Treatment: Other: back sleep positioning; Other: side sleep positioning

Detailed Description

The primary aim of this project is to determine the clinical effectiveness in infants with cleft palate (CP) of side-lying as compared to back-lying sleep positioning in reducing oxygen desaturation resulting from obstructive sleep apnoea (OSA). This will be achieved:

• comparing oxygen saturation during sleep in the side- and back-lying positions at 1 month of age.
• comparing sleep quality between the side-lying and back-lying groups using a parental questionnaire.
• co-developing national recommendations with parents regarding sleep position for infants with CP.

A randomised controlled trial (RCT) of side-lying compared with back-lying sleep positioning in reducing oxygen desaturation resulting from OSA in infants with CP. The design and conduct of the study will benefit from lessons learned from the feasibility and other previous studies. All parents in the feasibility study indicated strong interest to participate in further studies evaluating the effects of sleep position. Infants meeting the eligibility criteria will be randomised to side-lying or back-lying in a ratio 1:1 using a minimisation routine incorporating a random element to reduce predictability. Minimisation factors will be clinical site and syndrome suspected or indicated (yes / no). Allocations will be delivered via a password-protected web-based system. The allocated position will only be used on the day(s) when the infant is monitored for the study purposes. Thereafter, parents will be free to revert back to the standard sleep position as advised by their cleft centre, should it be different than that used for the monitoring period. All centres represented at the preparatory meeting with the United Kingdom (UK) Lead Clinical Nurse Specialist group, confirmed that the side-lying position was recommended in some infants at their centre, irrespective of whether it was the standard advice used. As such, all centres had experience of the side-lying position. It was decided not to change the specific advice that centres give to parents regarding how to position the infant in a side-lying position, but any standard written or verbal information would be collected by the study documents.

An internal pilot will investigate participants' opinions about their participation in the study. Using bespoke questionnaires participants' experience will be assessed and it will be decided how it could be improved. After 6 months questionnaire results will be analysed and if necessary study amendments will be put in place to reflect participants' opinions.

Data from the feasibility study and published studies have reported estimates of the standard deviation (SD) of the primary outcome ODI-4 in the side-lying infants at four weeks to range from 8 to 11 units, with a higher SD observed in the back-lying group. The observed difference in mean ODI-4 between the side-lying and back-lying infant cohorts was 15 units (a standardised effect size of 0.91). Investigators considered a smaller but more realistic difference in means of five units to be a clinically important difference (SD 10), a standardised effect size of 0.5. The sample size calculation comparing two means with unequal variances for the primary outcome was, therefore, based on a standardised effect size of 0.5. To account for potential unequal variances in each group a variance ratio of 2 was used in the calculations. To detect a difference of 0.5 standard deviation score (SDS) with 80% power and alpha equal to 0.05 would require 96 infants to be monitored in each arm of the trial (a total of 192 participants). Informed by the multicentre feasibility and oximetry studies the sample size will be inflated to 244 participants in the RCT, to allow for potential attrition of 21%.

This will follow a pre-specified and approved statistical analysis plan. The primary analysis of the RCT data will use intention-to-treat. Baseline data will be analysed to assess the comparability of the demographic and clinical characteristics of the participants. Data from the trial arms will be compared using generalised linear models and adjusted for minimisation covariates where appropriate. Estimates of treatment effect size will be reported as differences in means for continuous outcomes, and risk ratios for dichotomous outcomes and reported along with 95% confidence intervals. Subgroup analyses will explore the effects of sleep position on infants with and without suspected associated syndromes through subgroup treatment interactions, at a stricter alpha level 0.01.

• Study Type: Interventional
• Enrollment (Estimated): 244
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ola Metryka; Phone Number: +44 (0)161 701 3543; Email: slumbrs@mft.nhs.uk

Study Locations

• United Kingdom
  • Birmingham, United Kingdom
    • Not yet recruiting
    • Birmingham Women's and Children's NHS Foundation Trust
    • Contact: Michelle Jones
  • Bristol, United Kingdom
    • Not yet recruiting
    • University Hospitals Bristol NHS Foundation Trust
    • Contact: Cathy Marsh
  • Cambridge, United Kingdom
    • Not yet recruiting
    • Cambridge University Hospitals NHS Foundation Trust
    • Contact: Melanie Lindup
  • Leeds, United Kingdom
    • Not yet recruiting
    • Leeds Teaching Hospitals NHS Trust
    • Contact: Emma Blair
  • Liverpool, United Kingdom
    • Not yet recruiting
    • Alder Hey Children's NHS Foundation Trust
    • Contact: Helen Robson
  • London, United Kingdom
    • Not yet recruiting
    • Great Ormond Street Hospital For Children NHS Foundation Trust
    • Contact: Helen Moreland
  • Manchester, United Kingdom
    • Recruiting
    • Manchester University NHS Foundation Trust
    • Contact: Helen Robson
  • Newcastle Upon Tyne, United Kingdom
    • Not yet recruiting
    • The Newcastle upon Tyne Hospitals NHS Foundation Trust
    • Contact: Chris Couhig
  • Nottingham, United Kingdom
    • Not yet recruiting
    • Nottingham University Hospitals NHS Trust
    • Contact: Heather Sahunta
  • Salisbury, United Kingdom
    • Not yet recruiting
    • Salisbury NHS Foundation Trust
    • Contact: Nichola Hudson
  • Swansea, United Kingdom
    • Not yet recruiting
    • Swansea Bay University Local Health Board
    • Contact: Michaela Rowe

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 weeks to 1 month (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Infants diagnosed with an isolated CP under the care of a collaborating centre
• Infants who are 3 to 5 weeks of age when monitored
• Parents willing to give consent and able to complete study procedures

Exclusion Criteria:

• Infants with associated cleft lip
• Infants born prematurely (before 37 week gestation or up to and including 36 weeks and 6 days)
• Infants with cardiorespiratory disease
• Infants requiring an intervention to assist with breathing (nasopharyngeal airway)
• Infants requiring an intervention to assist with feeding (nasogastric tube)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Back lying sleep position; sleep on the back	Other: back sleep positioning; sleeping on the back.
Experimental: Side lying sleep position; sleep on the side	Other: side sleep positioning; sleeping on the side

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxygen saturation during sleep at 1 month of age	Oxygen saturation during sleep at 1 month of age (expressed as 4% oxygen desaturation index, ODI-4). Oximetry is considered the mainstay of assessment of oxygenation in infants and will be the primary outcome measurement instrument. The ODI-4 represents the average number of times that oxygen saturation falls by at least 4% from baseline every hour.	1 month of age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SPO2 mean	mean oxygen saturation	completed at 1 month
SPO2 nadir	nadir oxygen saturation	completed at 1 month
Total sleep time	the proportion of total sleep time (TST) with oxygen saturation below: 97%, 95%, 90% and 80%	completed at 1 month.
Oxygen saturation during sleep at 1 month of age	Oxygen saturation during sleep at 1 month of age (expressed as 3% oxygen desaturation index, ODI-3). Oximetry is considered the mainstay of assessment of oxygenation in infants and will be the primary outcome measurement instrument. The ODI-3 represents the average number of times that oxygen saturation falls by at least 3% from baseline every hour.	1 month of age
Weight	child's weight	completed at 1 month.
Length	participant's length	1 month of age
Head circumference	participant's head circumference	1 month of age
Number of participants with Adverse events.	Number of participants experiencing Adverse events during the trial	From consent for up to 2 weeks

Collaborators and Investigators

• Sponsor: Manchester University NHS Foundation Trust
• Collaborators: University College, London; University Hospital Southampton NHS Foundation Trust; University of Manchester; National Institute for Health Research, United Kingdom; Salisbury NHS Foundation Trust; Centre for Trials Research, Cardiff University; Cleft Lip and Palate Association
• Investigators: Study Director: Iain Bruce, Prof, Manchester University NHS Foundation Trust

Publications and helpful links

General Publications

• Metryka A, Cuniffe C, Evans HJ, Gavlak JG, Hudson N, Kirby N, Lakhanpaul M, Lin YL, Murray C, Rajai A, Robson H, Schilder A, Walsh T, Bruce I. Study protocol for randomised clinical trial comparing the effectiveness of side-lying sleep positioning to back-lying at reducing oxygen desaturation resulting from obstructive sleep apnoea in infants with cleft palate (SLUMBRS2). BMJ Open. 2021 Apr 7;11(4):e049290. doi: 10.1136/bmjopen-2021-049290.

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2022
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: May 28, 2020
• First Submitted That Met QC Criteria: July 16, 2020
• First Posted (Actual): July 20, 2020

Study Record Updates

• Last Update Posted (Actual): August 31, 2023
• Last Update Submitted That Met QC Criteria: August 30, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Sleep; Sleep position; Infants with cleft palate
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Congenital Abnormalities; Musculoskeletal Diseases; Stomatognathic Diseases; Mouth Diseases; Mouth Abnormalities; Stomatognathic System Abnormalities; Jaw Abnormalities; Jaw Diseases; Maxillofacial Abnormalities; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Cleft Palate
• Other Study ID Numbers: B00785

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No