Nasal Olfactory Stimulation and Its Effect on Respiratory Drive in Preterm Infants (NOSE)

Nasal Olfactory Stimulation and Its Effect on Respiratory Drive in Preterm Infants - A Randomized Cross-over Study

This trial analyzes the effect of an olfactory stimulation with vanilla or strawberry aroma compared to placebo on desaturations and bradycardia in preterm infants with apnea of prematurity. Infants on continuous positive airway pressure (CPAP) support will be included and the aroma will be applied to the inner surface of the CPAP mask using designated scent pens. The trial uses a cross-over design. Infants are randomised to begin the study with either aroma or placebo which will be applied into the breathing mask every 3 to 4 hours during 12 hours for each of the two intervention periods. Identically looking pens with either aroma or placebo are used and patients, parents, medical staff and the study team are blinded to this allocation. Infants are monitored with an oximetry sensor to measure peripheral oxygen saturation (SpO2) and pulse rate.

Study Overview

• Status: Recruiting
• Conditions: Infant, Premature, Diseases; Apnea of Prematurity; Prematurity
• Intervention / Treatment: Other: Aroma; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Janine Thomann, MD; Phone Number: 0041432538774; Email: janine.thomann@usz.ch
• Study Contact Backup: Name: Christoph Rüegger, PD; Phone Number: 0041432539810; Email: christoph.rueegger@usz.ch

Study Locations

• Switzerland
  • Zürich, Switzerland, 8091
    • Recruiting
    • Department of Neonatology, Newborn Research, University Hospital and University of Zurich,
    • Contact: Janine Thomann, MD; Phone Number: +41432538774

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Gestational age at birth: 23 0/7 to 31 6/7 weeks
• Postnatal age: >72 hours old
• Respiratory support: nCPAP
• Treatment with caffeine citrate for apnea of prematurity
• Written informed consent by one of the patient's parents

Exclusion Criteria:

• Olfactory impairment such as choanal atresia
• Intraparenchymal intracranial hemorrhage or intraventricular hemorrhage with ventricular dilation
• Culture-proven sepsis during the study period or any acute clinical deterioration requiring an intervention such as intubation or a new start of antibiotic treatment.
• Severe congenital malformation adversely affecting life expectancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aroma; Preterm infants on CPAP support will be exposed to either vanilla or strawberry aroma. A pen with and without vanilla or strawberry aroma will be used to apply the aroma to the inner surface of the CPAP mask.	Other: Aroma; The study intervention is an olfactory stimulation with vanilla or strawberry aroma. The aroma will be applied to the inner surface of the nCPAP mask of preterm infants using designated scent pens every 3-4 hours over a period of 12 hours. The two aromas will be applied in blocks of 5 consecutive infants (5 infants vanilla, 5 infants strawberry, and so forth).
Placebo Comparator: Control; Preterm infants on CPAP support will be exposed to placebo. The placebo pen will contain the carrier solution and natural coloring agents but no aroma.	Other: Placebo; During the control intervention, identically looking placebo pens will be used to apply a colored carrier solution (without aroma) to the inner surface of the nCPAP mask of preterm infants in the same manner.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Paired difference in the combined number of desaturations and bradycardia	A desaturation is defined as a fall in the SpO2 to <80% for more than 10 seconds, a bradycardia is defined as a fall in heart rate <80 bpm for more than 10 seconds. Desaturation episodes and bradycardia separated by a time interval of five seconds or less will be counted as a single event. A desaturation episode as part of a bradycardia (or vice versa) will be counted as a two events. Peripheral oxygen saturation and heart rate will be monitored with an oximeter sensor placed around the infants' wrist or ankle and connected to the oximeter in 2 seconds averaging mode and maximum sensitivity.	12-hour recording periods for each intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Paired difference in fraction of inspired oxygen (FiO2)	Paired difference in oxygen requirement between the two intervention periods. The FiO2 will be measured by the infant ventilator and documented in the patient data management system	12-hour recording periods for each intervention
Paired difference in mean peripheral oxygen saturation	Paired difference in oxygen saturation between the two intervention periods. Peripheral oxygen saturation and heart rate will be monitored with an oximeter sensor placed around the infants' wrist or ankle and connected to the oximeter in 2 seconds averaging mode and maximum sensitivity.	12-hour recording periods for each intervention
Paired difference in time spent with peripheral oxygen saturations <80%	Paired difference in total time spent with an oxygen saturation <80% between intervention periods. Peripheral oxygen saturation and heart rate will be monitored with an oximeter sensor placed around the infants' wrist or ankle and connected to the oximeter in 2 seconds averaging mode and maximum sensitivity.	12-hour recording periods for each intervention
Paired difference in time spent with heart rate <80 bpm	Paired difference in total time spent with a heart rate <80 beats per minute between intervention periods. Peripheral oxygen saturation and heart rate will be monitored with an oximeter sensor placed around the infants' wrist or ankle and connected to the oximeter in 2 seconds averaging mode and maximum sensitivity.	12-hour recording periods for each intervention
Paired difference in mean respiratory rate (as counted by nurses and manually) documented according to clinical routine) and heart rate	Paired difference in mean respiratory rate between intervention periods. Respiratory rate will be counted and documented by nurses every 4 to 8 hours according to clinical standard and documented in the patient data management system.	12-hour recording periods for each intervention
Paired difference in the apnea score documented by nurses	Paired difference in the apnea score (objective scoring system for the number and severity of apneas during a dedicated time frame) between intervention periods. Definition of the apnea score: Cumulative number of bradycardia <80 bpm and desaturations <80% during sleep and unimpaired wakefulness. Score 1 for event without need for intervention, score 2 for event requiring tactile stimulation, score 3 for event requiring increase of FiO2, score 8 for event requiring mask ventilation.	12-hour recording periods for each intervention
Paired difference in desaturations requiring stimulation or increase in FiO2	Paired difference in the total number of desaturations requiring manual stimulation or an increase in supplemental oxygen between intervention periods. Manual stimulation will be documented by nurses in the patient data management system.	12-hour recording periods for each intervention
Paired difference in tolerance of enteral nutrition as assessed by gastric residuals (the amount of stomach liquid detected prior to the next meal, in mL)	Paired difference in amount of gastric residuals (mL) between intervention periods. Before each feed, nurses routinely aspirate orogastric tubes to check for the liquid volume and document the amount in mL in the patient data management system.	12-hour recording periods for each intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prespecified subgroup analyses of the primary outcome will be performed according to the type of aroma (vanilla or strawberry) that was administered.	A prespecified subgroup analysis for the primary outcome will be performed between infants receiving vanilla and strawberry aroma.	12-hour recording periods for each intervention

Collaborators and Investigators

• Sponsor: University of Zurich
• Collaborators: Bangerter-Rhyner Foundation
• Investigators: Principal Investigator: Janine Thomann, MD, Department of Neonatology, University Hospital and University of Zurich, Zurich, Switzerland

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2023
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: May 1, 2023
• First Submitted That Met QC Criteria: May 23, 2023
• First Posted (Actual): May 30, 2023

Study Record Updates

• Last Update Posted (Actual): July 28, 2023
• Last Update Submitted That Met QC Criteria: July 25, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Olfactory stimulation
• Additional Relevant MeSH Terms: Infant, Newborn, Diseases; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Infant, Premature, Diseases; Premature Birth
• Other Study ID Numbers: NOSE-Trial

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