Pilot Study to Evaluate Doses of Mechanical Stimulus on the Effectiveness of Preterm Breathing

Effect of 9 Doses of Dorsal Mechanical Stimulus on Volume Respiratory Measures on Healthy Preterms: a Pilot Study

The goal of this clinical trial is to compare, in healthy preterm babies, 9 doses of dorsal mechanical stimuli, in order to answer:

• if there is a dose of dorsal mechanical stimuli that improves the basal respiration.

Participants will be stimulated through a cotton shirt for one minute with each dose, while respiratory measures will be taken through a nasobuccal mask, slightly tightened by the investigator staff. All time, babies are going to be monitored and assessing that they are comfortable.

Study Overview

• Status: Completed
• Conditions: Intermittent Hypoxia; Apnea of Prematurity
• Intervention / Treatment: Device: 20 per minute stimulus; Device: 30 per minute stimulus; Device: 40 per minute stimulus

Detailed Description

Apnea of Prematurity (AOP) occurs in 90% of infants born at ≤34 weeks of gestation. Despite current treatments, these infants continue to experience intermittent hypoxia (IH) events, which lead to subsequent complications. Dorsal and extremity kinesthetic stimulation-commonly practiced in patients experiencing apnea-has been shown to trigger the infant's own respiratory effort. Several clinical studies have demonstrated that mechanized or reactive stimulation, performed with various devices and at different intensities, decreases the number of apneas and reduces the time spent with oxygen saturation levels below 90%, a measure of IH. However, there are also reports of no favorable effects with certain other stimulation mechanisms.

To study the kinesthetic mechanism, a pilot study was conducted on 10 healthy premature infants. The infants were dorsally stimulated using a surgical glove inflated by a mechanical ventilator at rates of 20 and 40 cycles per minute, applying a standardized stimulus independent of weight and gestational age. The main results showed that, during the stimulation period, the respiratory rate decreased by 19-50% compared to baseline (without stimulation), while oxygen saturation increased by 2-7 percentage points. Additionally, it was observed that synchronization of breathing with the dorsal stimulus occurred 0-77% of the time.

These observations could be explained by the assumption that premature infants achieved more effective breaths through stimulation, recruiting more alveolar units, and potentially triggering the Hering-Breuer reflex, which inhibits subsequent respiratory efforts. Although these findings were statistically significant based on the analysis of paired sample means, not all infants responded in the same way.

Method: A pilot study involving 10 healthy preterm infants (24-34 weeks gestational age) will be conducted. The infants will be stimulated on their backs with different combinations of lifting (3, 5, and 8 mm) and frequency (20, 30, and 40 cycles per minute) using a shirt equipped with an inflating-deflating actuator. The main outcome will be a comparison of minute ventilation and tidal volumes at baseline and with the different stimulation doses. The software "Rec Trial" will be used to record vital signs, operational settings, respiratory volumes, and patterns for repeated measures ANOVA analysis. The expected results are to find the optimal combination of lifting and frequency stimulus to optimize minute ventilation and/or detect relevant respiratory patterns that improve minute ventilation.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Chile
  • Area Metropolitana
    • Santiago, Area Metropolitana, Chile, 833-0024
      • Puc, Nicu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria: 24-34 weeks of birth gestational age (BGA) preterms, healthy -

Exclusion Criteria: respiratory support, thoracic or abdominal malformations-recent surgeries, hypotonic syndromes

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Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 3mm lifting stimulus; Respiratory volume measures, vital signs and respiratory mechanics will be evaluated in 10 healthy preterm, by dorsal stimulation causing a displacement of 3 mm , performed by 2 operators .	Device: 20 per minute stimulus; crossover randomized mechanical dorsal stimuli -for one minute each- at 20-rates per minute; Device: 30 per minute stimulus; crossover randomized mechanical dorsal stimuli -for one minute each- at 30 rates per minute; Device: 40 per minute stimulus; crossover randomized mechanical dorsal stimuli -for one minute each- at 40 rates per minute
Active Comparator: 5mm lifting stimulus; Respiratory volume measures, vital signs and respiratory mechanics will be evaluated in 10 healthy preterm, by dorsal stimulation causing a displacement of 5 mm , performed by 2 operators .	Device: 20 per minute stimulus; crossover randomized mechanical dorsal stimuli -for one minute each- at 20-rates per minute; Device: 30 per minute stimulus; crossover randomized mechanical dorsal stimuli -for one minute each- at 30 rates per minute; Device: 40 per minute stimulus; crossover randomized mechanical dorsal stimuli -for one minute each- at 40 rates per minute
Active Comparator: 8mm lifting stimulus; Respiratory volume measures, vital signs and respiratory mechanics will be evaluated in 10 healthy preterm, by dorsal stimulation causing a displacement of 8 mm , performed by 2 operators .	Device: 20 per minute stimulus; crossover randomized mechanical dorsal stimuli -for one minute each- at 20-rates per minute; Device: 30 per minute stimulus; crossover randomized mechanical dorsal stimuli -for one minute each- at 30 rates per minute; Device: 40 per minute stimulus; crossover randomized mechanical dorsal stimuli -for one minute each- at 40 rates per minute
No Intervention: Basal; Respiratory volume measures, vital signs and respiratory mechanics will be evaluated in 10 healthy preterm basal- without stimulation- performed by 2 operators .

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of mean of Tidal Volume(TV) between the doses of dorsal mechanical stimuli	repeated measures ANOVA for mean of Tidal Volume ( ml/kg)	1 minute for each intervention ( dose)
Comparison of mean of Minute Ventilation (MV) between the doses of dorsal mechanical stimuli	repeated measures ANOVA for mean of MV ( ml/kg/ min)	1 minute for each intervention ( dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of mean of Respiratory Rate (RR)between the doses of dorsal mechanical stimuli	repeated measures ANOVA for mean RR (rpm)	1 minute for each intervention ( dose)
Comparison of mean of Cardiac Rate (CR)between the doses of dorsal mechanical stimuli	repeated measures ANOVA for mean CR (rpm)	1 minute for each intervention ( dose)
Comparison of mean of percent of oxygen saturation (Sats) between the doses of dorsal mechanical stimuli	repeated measures ANOVA for mean Sats (percent)	1 minute for each intervention ( dose)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analyss of pattern of respiratory drive between the doses of dorsal mechanical stimuli	Qualitative description of the respiratory drive( synchronicity-asynchronicity)	1 minute for each intervention ( dose)
Risk manangement	Description of Adverse Events( Neonatal Infant Pain Score (NIPS) >2-skin reactions-Apnea- Desaturation)	45-60 minutes each patient

Collaborators and Investigators

• Sponsor: Pontificia Universidad Catolica de Chile
• Investigators: Study Director: Paulina A Toso, MD, Pontificia Universidad Catolica de Chile

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2022
• Primary Completion (Actual): March 31, 2023
• Study Completion (Actual): January 31, 2024

Study Registration Dates

• First Submitted: September 29, 2022
• First Submitted That Met QC Criteria: October 10, 2024
• First Posted (Actual): October 15, 2024

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: October 10, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: preterm; medical device; hypoxia
• Additional Relevant MeSH Terms: Signs and Symptoms, Respiratory; Hypoxia
• Other Study ID Numbers: 210406008

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
• product manufactured in and exported from the U.S.: No