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

NCT05878925 | Completed

• 1 other identifier: NOSE
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Apnea of Prematurity; Prematurity; Infant, Premature, Diseases

Keywords

Olfactory stimulation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Paired difference in fraction of inspired oxygen (FiO2)

  12-hour recording periods for each intervention

• Paired difference in mean peripheral oxygen saturation

  12-hour recording periods for each intervention

• Paired difference in time spent with peripheral oxygen saturations <80%

  12-hour recording periods for each intervention

• Paired difference in time spent with heart rate <80 bpm

  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

  12-hour recording periods for each intervention

Other Outcomes (1)

• Prespecified subgroup analyses of the primary outcome will be performed according to the type of aroma (vanilla or strawberry) that was administered.

  12-hour recording periods for each intervention

Study Arms (2)

Aroma

EXPERIMENTAL

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

Control

PLACEBO COMPARATOR

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

Interventions

Aroma OTHER

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).

Aroma

Placebo OTHER

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.

Control

Eligibility Criteria

• Age: 72 Hours+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Zurich: lead
• Bangerter-Rhyner Foundation: collaborator

Study Sites (1)

Department of Neonatology, Newborn Research, University Hospital and University of Zurich,

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Apnea; Premature Birth; Infant, Premature, Diseases

Interventions

Odorants

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Environment; Ecological and Environmental Phenomena; Biological Phenomena; Environment and Public Health

Study Officials

• Janine Thomann, MD

  Department of Neonatology, University Hospital and University of Zurich, Zurich, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: To blind the study team and the medical team, identically looking pens will be provided with and without vanilla or strawberry aroma.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2023
• First Posted: May 30, 2023
• Study Start: June 14, 2023
• Primary Completion: January 24, 2025
• Study Completion: January 24, 2025
• Last Updated: April 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)