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The Pharmacokinetics of Oral Methadone in the Treatment of Neonatal Abstinence Syndrome

This study is currently recruiting participants.
Verified January 2013 by Children's Hospital Medical Center, Cincinnati
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Jason Wiles, MD, Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier:
NCT01754324
First received: December 14, 2012
Last updated: January 25, 2013
Last verified: January 2013
History of Changes
  Purpose

The chronic use of opiate medications during pregnancy is a major public health challenge. Prolonged exposure to opiates in utero may result in withdrawal symptoms in infants commonly referred to as neonatal abstinence syndrome (NAS). Signs of NAS may include irritability, high-pitched crying, muscle tightness, seizures, diarrhea, vomiting, poor feeding, and unstable body temperature. Many infants may be treated by supportive (non-pharmacological) therapy by minimizing stimulation, cuddling, responding promptly to hunger cues, and other comfort care. However, some infants continue to show severe symptoms of withdrawal despite these interventions. In these cases, infants may be treated with medications (pharmacological therapy). Although it has been several decades since the first descriptions of NAS, there still remains limited information with regards to the most effective treatment. We hypothesize that medical treatment protocols of NAS with methadone can be optimized by better understanding what the body does to the drug (the population-based pharmacokinetics of methadone).


Condition Intervention Phase
Neonatal Abstinence Syndrome
 Drug: Methadone
 Phase 1

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Utility and Pharmacokinetics of Oral Methadone in the Treatment of Neonatal Abstinence Syndrome in Neonates

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Children's Hospital Medical Center, Cincinnati:

Primary Outcome Measures:
  • Methadone and EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine) blood concentration [ Time Frame: Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks). ] [ Designated as safety issue: No ]
    Timed blood samples will be collected to estimate pharmacokinetic parameters of oral methadone and its major metabolite EDDP using population pharmacokinetic methods.


Secondary Outcome Measures:
  • Failed Protocol Wean [ Time Frame: Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks). ] [ Designated as safety issue: No ]
    Blood specimens for the analysis of methadone and EDDP concentrations will be obtained from infants who do not tolerate the standard methadone dosing taper to investigate its utility in identifying rapid metabolizers of methadone.

  • Number of participants requiring adjunctive pharmacological treatment [ Time Frame: Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks). ] [ Designated as safety issue: No ]
    This endpoint will look at the number of patients who require supplemental phenobarbital in the treatment of NAS symptoms.

  • Length of hospitalization [ Time Frame: Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks). ] [ Designated as safety issue: No ]
    This endpoint will describe the number of days infants were hospitalized for treatment of NAS.

  • Readmission to the hospital [ Time Frame: Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks) and will complete a follow-up survey up to 2 weeks after hospital discharge. ] [ Designated as safety issue: No ]
    This endpoint will describe the number of infants treated for NAS who later developed withdrawal symptoms after discharge that required readmission to the hospital.

  • Clinical resolution of NAS symptoms [ Time Frame: Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks) and will complete a follow-up survey up to 2 weeks after hospital discharge. ] [ Designated as safety issue: No ]
    The length of medical therapy with oral methadone (in days) required to result in the clinical resolution of NAS symptoms will be measured.


Estimated Enrollment: 20
Study Start Date: December 2012
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Methadone
All infants requiring pharmacological treatment of their NAS symptoms are treated with a standardized protocol utilizing oral methadone. This treatment protocol has been the standard of care for infants with NAS at our institution for many years. Infants enrolled in this study will have blood samples drawn at predetermined times in order to obtain information regarding the pharmacokinetics of oral methadone in this population.
 Drug: Methadone
The starting dose of the protocol is 0.05mg/kg by mouth given every 6 hours and gradually decreased in a stepwise, standardized fashion.
Other Name: methadone hydrochloride

  Eligibility

Ages Eligible for Study:   up to 1 Month
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Infants diagnosed with Neonatal Abstinence Syndrome and are treated with oral methadone.

Criteria

Inclusion Criteria:

  1. Chronic in utero exposure to opiates
  2. Term infant, greater than or equal to 37 weeks gestation
  3. Failure of non-pharmacologic treatment of NAS
  4. Infant meets criteria for pharmacologic treatment of NAS as determined by physical findings consistent with drug withdrawal and Finnegan scoring system
  5. The attending neonatologist chooses to treat the qualifying infant with oral methadone.

Exclusion Criteria:

  1. Prematurity
  2. Congenital Abnormalities
  3. Acutely ill neonates
  4. Confounding medical illness necessitating therapy with opiates other than for NAS
  5. Neonates whose only exposure to opiates were narcotics administered during labor
  6. Infants who are wards of the state
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01754324

Contacts
Contact: Jason R Wiles, MD 513-636-3149 jason.wiles@cchmc.org
Contact: Henry Akinbi, MD 513-636-8915 henry.akinbi@cchmc.org

Locations
United States, Ohio
The University Hospital Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Jason R Wiles, MD         jason.wiles@cchmc.org    
Principal Investigator: Jason R Wiles, MD            
Mercy Hospital Anderson Recruiting
Cincinnati, Ohio, United States, 45255
Contact: Laura Ward, MD         laura.ward@cchmc.org    
Principal Investigator: Laura Ward, MD            
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Principal Investigator: Jason R Wiles, MD Children's Hospital Medical Center, Cincinnati
Principal Investigator: Henry Akinbi, MD Children's Hospital Medical Center, Cincinnati
Principal Investigator: Alexander Vinks, PharmD, PhD Children's Hospital Medical Center, Cincinnati
  More Information

No publications provided

Responsible Party: Jason Wiles, MD, Neonatology Fellow, Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT01754324     History of Changes
Other Study ID Numbers: CCHMC-PK-1, 1T32HD069054
Study First Received: December 14, 2012
Last Updated: January 25, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Children's Hospital Medical Center, Cincinnati:
Neonatal Abstinence Syndrome
Pharmacokinetics
Methadone
Neonate
Newborn

Additional relevant MeSH terms:
Infant, Newborn, Diseases
Neonatal Abstinence Syndrome
Substance-Related Disorders
Mental Disorders
Methadone
Analgesics, Opioid
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
 Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Central Nervous System Depressants
Antitussive Agents
Respiratory System Agents
Narcotics

ClinicalTrials.gov processed this record on May 19, 2013