Clinical trial NCT03097484
Conditions: Neonatal Abstinence Syndrome Aromatherapy
Sponsor: John M. Daniel
Start date: 2015-07-25; Completion date: 2017-04-30
Enrollment: 38 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Determine the effectiveness of lavender and chamomile aromatherapy of mitigation of symptoms of Neonatal Abstinence Syndrome

Detailed description:
The United States, Appalachia, Eastern Kentucky in particular, is in the midst of a major opioid abuse epidemic. This current epidemic is driven by misuse of prescription painkillers, i.e. Subutex and Saboxone. As prescription pills become more expensive and harder to acquire, addicts are seeking similar, cheaper drugs; such as heroin. From 1998 to 2011, the prevalence of opioid abuse and dependence amongst pregnant women has increased by 127%, from 1.7 per 1000 to 3.9 per 1000. Neonatal Abstinence Syndrome (NAS) or neonatal opioid withdrawal syndrome is a condition produces gastrointestinal and autonomic neurologic dysfunction. Infants with severe withdrawal experience dysregulation of autonomic functions, resulting in feeding difficulty, diarrhea, excessive sleepiness, and tremors.Nearly two thirds of all babies exposed to opioids during gestation will require admission to a neonatal intensive care unit for management of withdrawal symptoms. During a typical year the Neonatal Intensive Care Unit (NICU) at Kentucky Children's Hospital admits approximately 100-120 infants exhibiting NAS symptoms; these infants have a typical length of stay of 24 days if they require pharmacologic treatment.

The mainstay of treatment for NAS involves opioid replacement therapy with morphine to minimize withdrawal symptoms. Once symptoms are well controlled, the infant is said to have been "captured." At this point a slow weaning of his morphine dose occurs. The infants' clinical status is assessed with the Finnegan Scoring system, which examines symptoms such as crying, excessive sleepiness or difficulty sleeping, insomnia, or tremors along with objective findings such as temperature and respiratory rate.

In addition to pharmacotherapy, alternative and complementary medicine techniques are slowly entering the NAS treatment algorithm. Treatments such as music therapy infant massage, kangaroo care, aromatherapy, and acupressure are now employed in NICUs in addition to traditional opioids replacement. However, few studies exist in the literature to evaluate their effectiveness.

Aromatherapy is the practice of using natural essential oils to achieve a desired effect in an individual. Scents such as lavender and chamomile have been documented to have a soothing calming effect. Studies involving infants shown that lavender not only reduce crying and enhance sleep, but also reduce levels of salivary cortisol, a stress hormone. Additionally, aromatherapy is currently used as an adjunctive therapy at the University of Kentucky's Markey Cancer Center.

Salivary cortisol is a non-invasive biomarker that has proven useful for monitoring stress in neonates. It is a simple and painless method for monitoring the stress hormone cortisol. Salivary cortisol has been used successfully in infants as a method to assess infant stress associated with prone position versus supine positioning.These studies have shown that salivary cortisol levels vary with stressful or soothing stimuli.

To date, no dangerous or deleterious effects have been described from traditional inhalational use of aromatherapy or with salivary cortisol sampling. Studies have shown aromatherapy to be an effective adjunctive therapy by proving a calming effect. In our patient population it may prove to be a useful complimentary therapy ultimately reducing infant stress, hospital length of stay, and burden of opioid use. Additionally, salivary cortisol's ease of collection and non-invasive nature make it an ideal biomarker to study.

Arms: arm 1: These infants will receive aromatherapy, consisting of Lavender and Chamomile essential oils, in addition to standard care, which includes morphine replacement therapy, infant massage, PT, OT, and music therapy. arm 2: These infants receive standard care ONLY, which includes morphine replacement therapy, infant massage, PT, OT, and music therapy.
Interventions: intervention 1: lavender and chamomile essential oils
Intervention descriptions: intervention 1: Our patches are obtained from BioEsse Technologies™. Each patch contains a 50:50 mixture of Lavender and Chamomile essential oils in a 55 microliter standard dose patch. The patches release the aromatherapy over a 2-8 hours period and the diffusion rate of each patch is identical. The back of the patch is layered with a hypoallergenic medical grade adhesive, similar to the material found on ECG leads.

Protocol documents:
Prot_SAP_000.pdf: 
STUDY PROTOCOL 
TITLE: AROMATHERAPY AS AN ADJUNCTIVE THERAPY FOR NEONATAL 
ABSTINENCE SYNDROME 
 
NCT: 03097484 
 
ADDRESS:  DEPARTMENT OF PEDIATRICS 
DIVISION OF NEONATOLOGY 
UNIVERSITY OF KENTUCKY  
800 ROSE ST, MS477 
LEXINGTON KY 40536 
 
FUNDING: DIVISION OF NEONATOLOGY 
 
ABBREVIATIONS: NAS, NEONATAL ABSTINENCE SYNDROME 
 
 
 
DOCUMENT DATE: MARCH 27, 2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
STUDY BACKGROUND 
 
The United States, Appalachia, Eastern Kentucky in particular, is in the midst of a major 
opioid abuse epidemic. This current epidemic is driven by misuse of prescription 
painkillers, i.e. Subutex and Saboxone. As prescription pills become more expensive and 
harder to acquire, addicts are seeking similar, cheaper drugs; such as heroin. From 1998 
to 2011, the prevalence of opioid abuse and dependence amongst pregnant women has 
increased by 127%, from 1.7 per 1000 to 3.9 per 1000. Neonatal Abstinence Syndrome 
(NAS) or neonatal opioid withdrawal syndrome is a condition produces gastrointestinal 
and autonomic neurologic dysfunction. Infants with severe withdrawal experience 
dysregulation of autonomic functions, resulting in feeding difficulty, diarrhea, excessive 
sleepiness, and tremors. Nearly two thirds of all babies exposed to opioids during 
gestation will require admission to a neonatal intensive care unit for management of 
withdrawal symptoms. During a typical year the Neonatal Intensive Care Unit (NICU) at 
Kentucky Children’s Hospital admits approximately 100-120 infants exhibiting NAS 
symptoms; these infants have a typical length of stay of 24 days if they require 
pharmacologic treatment. 
 
The mainstay of treatment for NAS involves opioid replacement therapy with morphine to 
minimize withdrawal symptoms. Once symptoms are well controlled, the infant is said to 
have been “captured.” At this point a slow weaning of his morphine dose occurs. The 
infants’ clinical status is assessed with the Finnegan Scoring system, which examines 
symptoms such as crying, excessive sleepiness or difficulty sleeping, insomnia, or 
tremors along with objective findings such as temperature and respiratory rate.  
 
In addition to pharmacotherapy, alternative and complementary medicine techniques are 
slowly entering the NAS treatment algorithm. Treatments such as music therapy infant 
massage, kangaroo care, aromatherapy, and acupressure are now employed in NICUs 
in addition to traditional opioids replacement. However, few studies exist in the literature 
to evaluate their effectiveness. 
Aromatherapy is the practice of using natural essential oils to achieve a desired effect in 
an individual. Scents such as lavender and chamomile have been documented to have a 
soothing calming effect. Studies involving infants shown that lavender not only reduce 
crying and enhance sleep, but also reduce levels of salivary cortisol, a stress hormone. 
Additionally, aromatherapy is currently used as an adjunctive therapy at the University of 
Kentucky’s Markey Cancer Center. 
 
Salivary cortisol is a non-invasive biomarker that has proven useful for monitoring stress 
in neonates. It is a simple and painless method for monitoring the stress hormone cortisol. 
Salivary cortisol has been used successfully in infants as a method to assess infant stress 
associated with prone position versus supine positioning. These studies have shown that 
salivary cortisol levels vary with stressful or soothing stimuli.  


 
To date, no dangerous or deleterious effects have been described from traditional 
inhalational use of aromatherapy or with salivary cortisol sampling. Studies have shown 
aromatherapy to be an effective adjunctive therapy by proving a calming effect. In our 
patient population it may prove to be a useful complimentary therapy ultimately reducing 
infant stress, hospital length of stay, and burden of opioid use. Additionally, salivary 
cortisol’s ease of collection and non-invasive nature make it an ideal biomarker to study. 
 
 
INCLUSION/EXCLUSION CRITERIA 
Inclusion Criteria: 
 - Infants greater than or equal to 36 weeks EGA 
 - Intrauterine opioid exposure 
 - Primary diagnosis of NAS 
 - Parental permission to participate 
 
 
Exclusion Criteria: 
 - Infants less than 36 weeks EGA 
 - Major congenital anomalies 
 - Latrogenic drug withdrawal 
 - Diagnosis of infection or respiratory distress 
 - Prior initiation of opioid replacement therapy 
 - Non-English speaking 
 - Infants with respiratory conditions 
 
 
ENROLLMENT 
 
Patients will be evaluated at admission or transfer to the University of Kentucky NICU and 
consent obtained from the mother. Patients will be randomized to one of two groups using 
block randomization in groups of four. The study will not be blinded (open-label). 
 
 
STANDARD OF CARE AND INTERVENTION 
 
Standard of care will include quiet environment, occupational therapy, music therapy and 
infant massage. Kangaroo care and breast feeding will be encouraged based on clinical 
recommendations.  
 
Interventional treatment will include all aspects of the standard of care in addition to 
aromatherapy. Patches will be obtained from BioEsse Technologies™ and will have an 
80:20 mixture of Lavender and Chamomile in a 55-microliter standard dose. When 
activated, each patch releases, the mixture over a 2-8 hour period by design and a 


constant diffusion rate. These will be attached to a positioning device placed in the infant’s 
bassinet 6-8 inches from the infant’s nose for a period of 4 hours twice a day. 
 
 
 
ASSESSMENT 
 
Comfort levels will be assessed using the MOTHER-NAS scoring system. After three 
consecutive scores of greater than or equal to 9 or two consecutive scores of greater than 
or equal to 13, replacement morphine (0.05mg/kg/dose every three hours) will be initiated. 
After 48 hours of symptom control, morphine will be weaned by 0.02mg/day. Any 
significant increase in scores that accompanied the wean will induce a return to the 
previous dose. 
 
DATA COLLECTION AND STATISTICAL ANALYSIS PLAN 
 
Data will be collected from hospital electronic medical records and stored in a secure 
manner. Data will include: 1) date of birth, 2) date of admission, 3) birth weight, 4) gender, 
5) APGAR scores, 6) mode of delivery, 7) place of birth, 8) type of prenatal drug exposure, 
9) prenatal care, 10) Finnegan scores, 11) average daily heart rate, 12) daily morphine 
dose, 13) total morphine dose per day, 14) length of treatment, and 15) length of 
hospitalization. 
 
Data will be analyzed using standard statistical techniques. The two treatment groups will 
be compared with a two-tailed t-test, while dichotomous variables will be examined with 
a Chi-Square test. Statistical significance will be set at p=0.05. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
Anticipated CONSORT Diagram showing the flow of participants through each 
stage of the trial.