Apnea of PrematurityNCT02641249
Non-invasive Intervention for Apnea of Prematurity
A study testing Vibration in people with Apnea of Prematurity and Hypoxia, run by University of California, Los Angeles at 2 sites in United States.
Trial summary
Purpose of Study: Apnea of Prematurity (AOP) is common, affecting the majority of infants born <34 weeks gestational age (GA). Apnea is accompanied by intermittent hypoxia (IH), which contributes to multiple pathologies, including retinopathy of prematurity (ROP), sympathetic ganglia injury, impaired pancreatic islet… Read more about this study
- Who is it for?
- Ages 1 week and older
- Conditions the study is for
- Apnea of Prematurity, Hypoxia, Bradycardia
- What is being tested?
- Vibration
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2014to Feb 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 week and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Gestational age > 23 weeks, < 34 weeks
- At least 1 week old at recruitment
- Diagnosis of apnea of prematurity (AOP)
- Caffeine treatment will not be an exclusion
Who cannot join
- Infants with major congenital anomalies/malformations which will influence central nervous system and long-term outcomes in these infants, such as cardiac anomalies (except for Patent Ductus Arteriosus or Ventricular Septal Defect) or major neurological malformations, like meningoencephalocele, holoprosencephaly etc.
- Neonates who have apnea from airway issues like laryngomalacia or tracheomalacia
- Neonates with history of hypoxic ischemic encephalopathy or Grade IV intraventricular hemorrhage
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Ronald Reagan Medical Center - UCLA
Los Angeles, California, 90095
Santa Monica UCLA Mecial Center
Santa Monica, California, 90404
About this study
Official title: Neuromodulation of Limb Proprioceptive Afferents Using a Vibratory Device to Decrease Apnea, Intermittent Hypoxia and Bradycardia of Prematurity.
Purpose of Study: Apnea of Prematurity (AOP) is common, affecting the majority of infants born <34 weeks gestational age (GA). Apnea is accompanied by intermittent hypoxia (IH), which contributes to multiple pathologies, including retinopathy of prematurity (ROP), sympathetic ganglia injury, impaired pancreatic islet cell and bone development, and neurodevelopmental disabilities. Standard of care for AOP/IH includes prone positioning, positive pressure ventilation, and caffeine therapy, none of which is optimal. The objective is to support breathing in premature infants by using a simple, non-invasive vibratory device placed over limb proprioceptor fibers, an intervention using the principle that limb movements facilitate breathing.
Methods Used: Premature infants (23-34 wks GA) with clinical evidence of AOP/IH were enrolled 1 week after birth. Caffeine therapy was not a reason for exclusion. Small vibration devices were placed on one hand and one foot and activated in a 6 hour ON/OFF sequence for a total of 24 hours. Heart rate, respiratory rate, oxygen saturation (SpO2), and breathing pauses were continuously collected.
Read the detailed description
Aim: To study the effect of limb proprioceptive stimulation using a vibratory device on apneic events, intermittent hypoxic episodes and bradycardias in a premature infant with apnea of prematurity.
The objective is to provide support and to assist impaired ventilation and oxygenation in apnea of prematurity (AOP). Recurrent apnea and accompanying resultant intermittent hypoxic (IH) episodes are significant concerns commonly encountered in premature infants, and optimal management is a challenge to neonatologists. AOP is defined as "a pause of breathing for more than 15-20 seconds or accompanied by oxygen desaturation (SpO2<80% for>4s) and bradycardia (heart rate<2/3 of baseline for>4s), in infants born less than 37 weeks of gestation [Moriette G et al., 2010]. When these pauses are longer (> 15s), they are frequently prolonged by obstructed inspiratory efforts, most likely secondary to loss of upper airway tonic activity [Martin RJ et al., 2012]. In extremely low birth weight (ELBW) infants, the incidence of IH progressively increases over the first 4 weeks of postnatal life, followed by a plateau and subsequent decline between 6-8 weeks.
The incidence of AOP correlates inversely with gestational age and birth weight. Nearly all infants born <29 weeks gestation or <1,000 g [Robertson CM et al., 2009], 54% at 30 to 31 weeks, 15% at 32 to 33 weeks, and 7% at 34 to 35 weeks gestation exhibit AOP [Martin RJ et al]. Both animal and human evidence show that immature or impaired respiratory control and the resultant IH exposure contribute to a variety of pathophysiologic issues via pro-inflammatory and/or pro-oxidant cascade as well as cellular mechanisms, e.g., apoptosis, leading to acute and chronic morbidities (e.g. retinopathy of prematurity, altered growth and cardiovascular regulation, disrupting zinc homeostasis which hampers insulin production and there by predisposing to diabetes in later life, cerebellar injuries and neurodevelopmental disabilities) [Martin RJ et al., 2004, Pae EK et al., 2011, 2014, ].
Current standard of care for AOP includes prone positioning, continuous positive airway pressure (CPAP) or nasal intermittent positive pressure ventilation (NIPPV) to prevent pharyngeal collapse and alveolar atelectasis, and methylxanthine therapy (caffeine, theophylline), which is the mainstay of treatment of central apnea [Reher et al., 2008; Pantalitschka T et al., 2009; Moretti C et al., 2012; Henderson-Smart DJ et al., 2010]. Apart from prone positioning, none of these interventions are optimal for early development. CPAP masks will distort the bony facial structure in early development, and methylxanthine interventions pose serious questions of neural development interactions.
Hypothesis: Applying slight vibration to the limbs will reduce the number of breathing pauses, intermittent hypoxic episodes and bradycardias in apnea of prematurity.
- Conditions
- Apnea of Prematurity, Hypoxia, Bradycardia
- Being tested
- Vibration
- Medical subject headings
- Apnea, Hypoxia, Bradycardia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VibrationDevice
Also called (no generic name)
A device providing vibrations is placed on the subject and vibration is turned on and off in a 6 hour on/off sequence. Heart rate, respiratory pauses and oxygen saturation are compared during vibration (intervention) and without vibration (no intervention) in the same subject.
| Study group | Role | What they receive |
|---|---|---|
| No vibration | No intervention | In the same subject cardiorespiratory parameters - heart rate, respiratory rate and oxygen saturation were compared during the procedure (vibration) and without procedure (no vibration). The same subject had both control and treatment periods. |
| Vibration | Experimental | In the same subject cardiorespiratory parameters - heart rate, respiratory rate and oxygen saturation were compared during the procedure (vibration) and without procedure (no vibration). The same subject had both control and treatment periods. Receives: Device: Vibration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Total Number of Episodes of Apnea/Breathing Pauses During Intervention and Without Intervention
The total number of apneas/breathing pauses will be compared during periods of vibration (intervention) to periods of no vibrations (no intervention).
Measured: 12 hours of intervention/12 hours of no intervention
Secondary outcomes (2)
Change in the Total Number of Intermittent Hypoxic Episodes to <90% Lasting >5 Seconds/Episode During the Intervention and Without Intervention
The total number of intermittent hypoxic episodes to <90% (pulse oximetry) lasting >5 seconds/episode will be compared during periods of vibration (intervention) to periods of no vibrations (no intervention).
Measured: 12 hours of intervention/12 hours of no intervention
Change in the Total Number of Bradycardia Episodes (<100 Beats Per Minute (Bpm), at Least 5 Seconds Long) During Intervention and Without the Intervention
The total number of bradycardia episodes to <100 bpm lasting >5 seconds/episode will be compared during periods of vibration (intervention) to periods of no vibrations (no intervention).
Measured: 12 hours of intervention/12 hours of no intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2015 (estimated)
- Study startOct 2014
- Primary completionAug 2015
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Apnea of PrematurityStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- In the same subject there were 2 periods: Arm 1. 'No intervention' period (no vibrations) - two 6 hour epochs - total of 12 hours of 'No intervention' Arm 2. Experimental period (with vibrations) - two 6 hour epochs - total of 12 hours of 'vibration intervention' In the same subjects cardiorespiratory parameters - heart rate, respiratory rate and oxygen saturation were compared during the experimental period (vibration) and druing the no intervention period (no vibration).
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kalpashri Kesavan, University of California, Los Angeles
- Investigators
- Kalpashri Kesavan, MBBS, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02641249
- Sponsor's protocol ID
- IRB#14-000804
- Status last verified
- Nov 2016
- First submitted
- 18 Dec 2015
- Last updated
- 9 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Available online as supporting information: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0157349#sec019
Publications
Kesavan K, Frank P, Cordero DM, Benharash P, Harper RM. Neuromodulation of Limb Proprioceptive Afferents Decreases Apnea of Prematurity and Accompanying Intermittent Hypoxia and Bradycardia. PLoS One. 2016 Jun 15;11(6):e0157349. doi: 10.1371/journal.pone.0157349. eCollection 2016.
PubMed 27304988
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuromodulation of Limb Proprioceptive Afferents Using a Vibratory Device to Decrease Apnea, Intermittent Hypoxia and Bradycardia of Prematurity.
- ClinicalTrials.gov ID
- NCT02641249
- Acronym / sponsor ID
- IRB#14-000804
- Conditions
- Apnea of Prematurity, Hypoxia, Bradycardia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Study start
- Oct 2014
- Primary completion
- Aug 2015 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 29 Dec 2015 (estimated)
- Results
- Posted 9 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Purpose of Study: Apnea of Prematurity (AOP) is common, affecting the majority of infants born <34 weeks gestational age (GA). Apnea is accompanied by intermittent hypoxia (IH), which contributes to multiple pathologies, including retinopathy of prematurity (ROP), sympathetic ganglia injury, impaired pancreatic islet cell and bone development, and neurodevelopmental disabilities. Standard of care for AOP/IH includes prone positioning, positive pressure ventilation, and caffeine therapy, none of which is optimal. The objective is to support breathing in premature infants by using a simple, non-invasive vibratory device placed over limb proprioceptor fibers, an intervention using the principle that limb movements facilitate breathing.
Methods Used: Premature infants (23-34 wks GA) with clinical evidence of AOP/IH were enrolled 1 week after birth. Caffeine therapy was not a reason for exclusion. Small vibration devices were placed on one hand and one foot and activated in a 6 hour ON/OFF sequence for a total of 24 hours. Heart rate, respiratory rate, oxygen saturation (SpO2), and breathing pauses were continuously collected.
Detailed description
Aim: To study the effect of limb proprioceptive stimulation using a vibratory device on apneic events, intermittent hypoxic episodes and bradycardias in a premature infant with apnea of prematurity.
The objective is to provide support and to assist impaired ventilation and oxygenation in apnea of prematurity (AOP). Recurrent apnea and accompanying resultant intermittent hypoxic (IH) episodes are significant concerns commonly encountered in premature infants, and optimal management is a challenge to neonatologists. AOP is defined as "a pause of breathing for more than 15-20 seconds or accompanied by oxygen desaturation (SpO2<80% for>4s) and bradycardia (heart rate<2/3 of baseline for>4s), in infants born less than 37 weeks of gestation [Moriette G et al., 2010]. When these pauses are longer (> 15s), they are frequently prolonged by obstructed inspiratory efforts, most likely secondary to loss of upper airway tonic activity [Martin RJ et al., 2012]. In extremely low birth weight (ELBW) infants, the incidence of IH progressively increases over the first 4 weeks of postnatal life, followed by a plateau and subsequent decline between 6-8 weeks.
The incidence of AOP correlates inversely with gestational age and birth weight. Nearly all infants born <29 weeks gestation or <1,000 g [Robertson CM et al., 2009], 54% at 30 to 31 weeks, 15% at 32 to 33 weeks, and 7% at 34 to 35 weeks gestation exhibit AOP [Martin RJ et al]. Both animal and human evidence show that immature or impaired respiratory control and the resultant IH exposure contribute to a variety of pathophysiologic issues via pro-inflammatory and/or pro-oxidant cascade as well as cellular mechanisms, e.g., apoptosis, leading to acute and chronic morbidities (e.g. retinopathy of prematurity, altered growth and cardiovascular regulation, disrupting zinc homeostasis which hampers insulin production and there by predisposing to diabetes in later life, cerebellar injuries and neurodevelopmental disabilities) [Martin RJ et al., 2004, Pae EK et al., 2011, 2014, ].
Current standard of care for AOP includes prone positioning, continuous positive airway pressure (CPAP) or nasal intermittent positive pressure ventilation (NIPPV) to prevent pharyngeal collapse and alveolar atelectasis, and methylxanthine therapy (caffeine, theophylline), which is the mainstay of treatment of central apnea [Reher et al., 2008; Pantalitschka T et al., 2009; Moretti C et al., 2012; Henderson-Smart DJ et al., 2010]. Apart from prone positioning, none of these interventions are optimal for early development. CPAP masks will distort the bony facial structure in early development, and methylxanthine interventions pose serious questions of neural development interactions.
Hypothesis: Applying slight vibration to the limbs will reduce the number of breathing pauses, intermittent hypoxic episodes and bradycardias in apnea of prematurity.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- In the same subject there were 2 periods: Arm 1. 'No intervention' period (no vibrations) - two 6 hour epochs - total of 12 hours of 'No intervention' Arm 2. Experimental period (with vibrations) - two 6 hour epochs - total of 12 hours of 'vibration intervention' In the same subjects cardiorespiratory parameters - heart rate, respiratory rate and oxygen saturation were compared during the experimental period (vibration) and druing the no intervention period (no vibration).
| Arm | Type | Receives |
|---|---|---|
| No vibration | No intervention | –In the same subject cardiorespiratory parameters - heart rate, respiratory rate and oxygen saturation were compared during the procedure (vibration) and without procedure (no vibration). The same subject had both control and treatment periods. |
| Vibration | Experimental | Device: VibrationIn the same subject cardiorespiratory parameters - heart rate, respiratory rate and oxygen saturation were compared during the procedure (vibration) and without procedure (no vibration). The same subject had both control and treatment periods. |
Who may qualify
- Ages
- 1 week and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Gestational age > 23 weeks, < 34 weeks
- At least 1 week old at recruitment
- Diagnosis of apnea of prematurity (AOP)
- Caffeine treatment will not be an exclusion
Key exclusion criteria (3 listed)
- Infants with major congenital anomalies/malformations which will influence central nervous system and long-term outcomes in these infants, such as cardiac anomalies (except for Patent Ductus Arteriosus or Ventricular Septal Defect) or major neurological malformations, like meningoencephalocele, holoprosencephaly etc.
- Neonates who have apnea from airway issues like laryngomalacia or tracheomalacia
- Neonates with history of hypoxic ischemic encephalopathy or Grade IV intraventricular hemorrhage
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VibrationAlso: (no generic name)A device providing vibrations is placed on the subject and vibration is turned on and off in a 6 hour on/off sequence. Heart rate, respiratory pauses and oxygen saturation are compared during vibration (intervention) and without vibration (no intervention) in the same subject. | Device | Vibration |
Primary outcome
Change in Total Number of Episodes of Apnea/Breathing Pauses During Intervention and Without Intervention
Time frame: 12 hours of intervention/12 hours of no intervention
The total number of apneas/breathing pauses will be compared during periods of vibration (intervention) to periods of no vibrations (no intervention).
2 secondary outcomes
Change in the Total Number of Intermittent Hypoxic Episodes to <90% Lasting >5 Seconds/Episode During the Intervention and Without Intervention
Time frame: 12 hours of intervention/12 hours of no intervention
Change in the Total Number of Bradycardia Episodes (<100 Beats Per Minute (Bpm), at Least 5 Seconds Long) During Intervention and Without the Intervention
Time frame: 12 hours of intervention/12 hours of no intervention
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27304988Kesavan K, Frank P, Cordero DM, Benharash P, Harper RM. Neuromodulation of Limb Proprioceptive Afferents Decreases Apnea of Prematurity and Accompanying Intermittent Hypoxia and Bradycardia. PLoS One. 2016 Jun 15;11(6):e0157349. doi: 10.1371/journal.pone.0157349. eCollection 2016.
- Individual participant dataSharing planned: Yes. Available online as supporting information: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0157349#sec019
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kalpashri Kesavan, MBBS principal investigator
University of California, Los Angeles
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vibration in people with Apnea of Prematurity and Hypoxia, run by University of California, Los Angeles at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Total Number of Episodes of Apnea/Breathing Pauses During Intervention and Without Intervention (time frame: 12 hours of intervention/12 hours of no intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02641249, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2017.