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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01754324
Recruitment Status : Completed
First Posted : December 21, 2012
Last Update Posted : June 13, 2014
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief Summary:
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 or disease Intervention/treatment Phase
Neonatal Abstinence Syndrome Drug: Methadone Phase 1

Study Design

Study Type : Observational
Actual Enrollment : 20 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Utility and Pharmacokinetics of Oral Methadone in the Treatment of Neonatal Abstinence Syndrome in Neonates
Study Start Date : December 2012
Primary Completion Date : December 2013
Study Completion Date : December 2013

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U.S. FDA Resources

Groups and Cohorts

Group/Cohort Intervention/treatment
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


Outcome Measures

Primary Outcome Measures :
  1. 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). ]
    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 :
  1. Failed Protocol Wean [ Time Frame: Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks). ]
    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.

  2. 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). ]
    This endpoint will look at the number of patients who require supplemental phenobarbital in the treatment of NAS symptoms.

  3. Length of hospitalization [ Time Frame: Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks). ]
    This endpoint will describe the number of days infants were hospitalized for treatment of NAS.

  4. 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. ]
    This endpoint will describe the number of infants treated for NAS who later developed withdrawal symptoms after discharge that required readmission to the hospital.

  5. 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. ]
    The length of medical therapy with oral methadone (in days) required to result in the clinical resolution of NAS symptoms will be measured.


Eligibility Criteria

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Ages Eligible for Study:   up to 1 Month   (Child)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01754324


Locations
United States, Ohio
The University Hospital
Cincinnati, Ohio, United States, 45229
Mercy Hospital Anderson
Cincinnati, Ohio, United States, 45255
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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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
5T32HD069054 ( U.S. NIH Grant/Contract )
First Posted: December 21, 2012    Key Record Dates
Last Update Posted: June 13, 2014
Last Verified: June 2014

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

Additional relevant MeSH terms:
Syndrome
Neonatal Abstinence Syndrome
Disease
Pathologic Processes
Infant, Newborn, Diseases
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Methadone
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Antitussive Agents
Respiratory System Agents