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

Neonatal Abstinence Syndrome Clinical Trial

Official title:

The Utility and Pharmacokinetics of Oral Methadone in the Treatment of Neonatal Abstinence Syndrome in Neonates

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01754324
• Other study ID #: CCHMC-PK-1
• Secondary ID: 5T32HD069054
• Status: Completed
• Phase: Phase 1
• First received: December 14, 2012
• Last updated: June 12, 2014
• Start date: December 2012
• Est. completion date: December 2013

Study information

• Verified date: June 2014
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 1 Month

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Neonatal Abstinence Syndrome
• Syndrome

Intervention

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.

Locations

Country	Name	City	State
United States	Mercy Hospital Anderson	Cincinnati	Ohio
United States	The University Hospital	Cincinnati	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Methadone and EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine) blood concentration	Timed blood samples will be collected to estimate pharmacokinetic parameters of oral methadone and its major metabolite EDDP using population pharmacokinetic methods.	Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks).	No
Secondary	Failed Protocol Wean	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.	Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks).	No
Secondary	Number of participants requiring adjunctive pharmacological treatment	This endpoint will look at the number of patients who require supplemental phenobarbital in the treatment of NAS symptoms.	Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks).	No
Secondary	Length of hospitalization	This endpoint will describe the number of days infants were hospitalized for treatment of NAS.	Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks).	No
Secondary	Readmission to the hospital	This endpoint will describe the number of infants treated for NAS who later developed withdrawal symptoms after discharge that required readmission to the hospital.	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.	No
Secondary	Clinical resolution of NAS symptoms	The length of medical therapy with oral methadone (in days) required to result in the clinical resolution of NAS symptoms will be measured.	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.	No