Improving Outcomes in Neonatal Abstinence Syndrome
Information source: Tufts Medical Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Neonatal Abstinence Syndrome; Neonatal Opioid Withdrawal
Intervention: Neonatal Morphine Solution (Drug); Methadone (Drug); Phenobarbital (Drug)
Phase: Phase 3
Status: Recruiting
Sponsored by: Tufts Medical Center Official(s) and/or principal investigator(s): Jonathan Davis, MD, Principal Investigator, Affiliation: Tufts Medical Center Barry Lester, PhD, Principal Investigator, Affiliation: Women and Infant's Hospital
Overall contact: Jonathan Davis, MD, Phone: 617-636-5322, Email: jdavis@tuftsmedicalcenter.org
Summary
1: SPECIFIC AIM I: To compare treatment options for neonatal abstinence syndrome (NAS) due
to in-utero narcotic exposure. One hundred eighty four full-term infants with a diagnosis
of NAS requiring medications will be studied. Infants will be randomized to receive either
morphine or methadone. It is hypothesized that morphine treated infants will do better and
require fewer days in the hospital compared to methadone treated infants.
2. SPECIFIC AIM II: To evaluate the effects of NAS treatment on long-term neurodevelopmental
outcome. Infants will be evaluated with development testing at 18 months of age. It is
hypothesized that morphine treated infants will have better neurodevelopmental outcomes. It
is also hypothesized that neurobehavioral abnormalities identified at two weeks of age will
correlate with neurodevelopmental impairment at 18 months.
3: SPECIFIC AIM III: To determine if common genetic variations in the genes involving
narcotic action contribute to the severity of NAS. A DNA sample will be obtained from all
infants and analyzed for differences in 3 key genes. This will then be correlated with
short-term and long-term outcomes.
Clinical Details
Official title: Improving Outcomes in Neonatal Abstinence Syndrome
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Length of hospital stay
Secondary outcome: Total opioid daysMaximum daily dose of replacement opioid Mean Finnegan Score Need for a second NAS medication
Detailed description:
1: SPECIFIC AIM I: To compare the short term efficacy of morphine and methadone for the
treatment of NAS. One hundred eighty four term infants with a diagnosis of NAS requiring
pharmacotherapy will be studied. Infants born to mothers receiving adequate prenatal care
and maintained on opioid agonist medication during pregnancy will be eligible. Infants will
be randomized to receive either neonatal morphine solution or methadone in a double blind,
double dummy design. It is hypothesized that morphine treated infants will require
significantly fewer days in the hospital compared to methadone treated infants. While the
primary outcome is the total length of initial hospital stay (LOS), total LOS related to
NAS, total duration of medical treatment for NAS, the need for a second drug to control
symptoms, and infant growth will also be evaluated as important secondary outcomes by
medication group assignment.
2. SPECIFIC AIM II: To evaluate the effects of NAS treatment on long-term neurodevelopmental
outcome. Infants in both treatment groups will be evaluated at 18 months of age using the
Bayley III Scales of Infant Development. It is hypothesized that morphine treated infants
will have better neurodevelopmental outcomes at 18 months compared to methadone treated
infants. It is also hypothesized that neurobehavioral abnormalities (from either treatment
group) identified at two weeks of age using the NICU Network Neurobehavioral Scale (NNNS)
will correlate with neurodevelopmental impairment detected with the Bayley III. Early
identification of infants at highest risk for impaired development will facilitate
therapeutic interventions to improve outcome and decrease resource utilization.
3: SPECIFIC AIM III: To determine if single nucleotide polymorphisms (SNPs) in genes
controlling opioid pharmacodynamics contribute to the severity of NAS. SNP genotyping from
cord blood or buccal swabs will be obtained from all infants and correlated with short term
outcomes (Aim 1) and neurodevelopment assessments (Aim 2) to confirm that genetic variation
plays a major role in the severity and outcome of infants with NAS.
Eligibility
Minimum age: N/A.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion criteria:
1. Mother receiving methadone or buprenorphine (BPH) from a licensed physician or drug
treatment program, or an opioid prescribed by a licensed health care worker for
treatment of chronic pain.
2. Need for treatment of NAS by Finnegan Scoring criteria
3. Gestational age >37 weeks at birth defined by best obstetrical estimate
4. Medically stable in the opinion of the Attending Physician
5. Mother receiving "adequate" or "intermediate" prenatal care from a qualified
physician or midwife as defined by the Prenatal Care Adequacy Index
6. Singleton pregnancy
7. Mother able to provide informed consent
8. Infant able to take oral medications
Exclusion criteria:
1. Gestation <37 weeks at entry defined by best obstetrical estimate
2. Major congenital abnormalities including genetic syndromes
3. Serious medical illness such as sepsis, asphyxia, seizures, or respiratory failure
4. Mother abusing alcohol during pregnancy (average of 3 or more drinks per week in the
last 30 days)
5. Multiple gestations
6. Mother received "inadequate" prenatal care as defined by the Prenatal Care Adequacy
Index.
Locations and Contacts
Jonathan Davis, MD, Phone: 617-636-5322, Email: jdavis@tuftsmedicalcenter.org
Shands Jacksonville Medical Center, Jacksonville, Florida 32209, United States; Recruiting Mark Hudak, MD, Phone: 904-244-4242, Email: mark.hudak@jax.ufl.edu
Maine Medical Center, Portland, Maine, United States; Recruiting Peter Marro, MD, Email: MARROP@mmc.org Peter Marro, MD, Principal Investigator
Boston Medical Center, Boston, Massachusetts 02118, United States; Recruiting Elisha Wachman, MD, Phone: 617-414-3690, Email: Elisha.Wachman@bmc.org Michael Silverstein, MD, Principal Investigator Elisha Wachman, MD, Sub-Investigator
Tufts Medical Center, Boston, Massachusetts 02111, United States; Recruiting Jonathan Davis, MD, Phone: 617-636-5322, Email: jdavis@tuftsmedicalcenter.org Morgan R Newsome, DO, Phone: 617-636-2392, Email: mnewsome@tuftsmedicalcenter.org Jonathan Davis, MD, Principal Investigator
Baystate Medical Center, Springfield, Massachusetts 01199, United States; Recruiting Jeffrey Shenberger, MD, Phone: 413-794-5370, Email: jeffrey.shenberger@baystatehealth.org Jeffrey Shenberger, MD, Principal Investigator
University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15224, United States; Recruiting Debra L Bogen, MD, Phone: 412-692-6932, Email: bogendl@upmc.edu Debra L Bogen, MD, Principal Investigator
Women and Infant's Hospital of Rhode Island, Providence, Rhode Island 02908, United States; Recruiting Barry Lester, PhD, Phone: 401-453-7640, Email: BLester@WIHRI.org Barry Lester, PhD, Principal Investigator
Vanderbilt University, Nashville, Tennessee 37232, United States; Recruiting Barbara Engelhardt, MD, Phone: 615-322-3475, Email: Barbara.Engerhardt@vanderbilt.edu Barbara Engelhardt, MD, Principal Investigator
Additional Information
Related publications: Wachman EM, Hayes MJ, Brown MS, Paul J, Harvey-Wilkes K, Terrin N, Huggins GS, Aranda JV, Davis JM. Association of OPRM1 and COMT single-nucleotide polymorphisms with hospital length of stay and treatment of neonatal abstinence syndrome. JAMA. 2013 May 1;309(17):1821-7. doi: 10.1001/jama.2013.3411. Sarkar S, Donn SM. Management of neonatal abstinence syndrome in neonatal intensive care units: a national survey. J Perinatol. 2006 Jan 1;26(1):15-7. Lainwala S, Brown ER, Weinschenk NP, Blackwell MT, Hagadorn JI. A retrospective study of length of hospital stay in infants treated for neonatal abstinence syndrome with methadone versus oral morphine preparations. Adv Neonatal Care. 2005 Oct;5(5):265-72. Lötsch J, Skarke C, Liefhold J, Geisslinger G. Genetic predictors of the clinical response to opioid analgesics: clinical utility and future perspectives. Clin Pharmacokinet. 2004;43(14):983-1013. Review. Jansson LM, Velez M, Harrow C. The opioid-exposed newborn: assessment and pharmacologic management. J Opioid Manag. 2009 Jan-Feb;5(1):47-55. Review. Osborn DA, Jeffery HE, Cole MJ. Opiate treatment for opiate withdrawal in newborn infants. Cochrane Database Syst Rev. 2010 Oct 6;(10):CD002059. doi: 10.1002/14651858.CD002059.pub3. Review. Jones HE, Kaltenbach K, Heil SH, Stine SM, Coyle MG, Arria AM, O'Grady KE, Selby P, Martin PR, Fischer G. Neonatal abstinence syndrome after methadone or buprenorphine exposure. N Engl J Med. 2010 Dec 9;363(24):2320-31. doi: 10.1056/NEJMoa1005359.
Starting date: September 2013
Last updated: May 15, 2015
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