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

NCT01754324 | Completed

• 2 other identifiers: CCHMC-PK-15T32HD069054
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 2

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).

Conditions

Neonatal Abstinence Syndrome

Keywords

Neonatal Abstinence Syndrome; Pharmacokinetics; Methadone; Neonate; Newborn

Outcome Measures

Primary Outcomes (1)

• 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).

Secondary Outcomes (5)

• Failed Protocol Wean

  Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks).

• Number of participants requiring adjunctive pharmacological treatment

  Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks).

• Length of hospitalization

  Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks).

• 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.

• Clinical resolution of NAS symptoms

  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.

Study Arms (1)

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

Interventions

Methadone DRUG

The starting dose of the protocol is 0.05mg/kg by mouth given every 6 hours and gradually decreased in a stepwise, standardized fashion.

Also known as: methadone hydrochloride

Methadone

Eligibility Criteria

• Age: Up to 1 Month
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

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

You may not qualify if:

• Prematurity
• Congenital Abnormalities
• Acutely ill neonates
• Confounding medical illness necessitating therapy with opiates other than for NAS
• Neonates whose only exposure to opiates were narcotics administered during labor
• Infants who are wards of the state

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (2)

The University Hospital

Cincinnati, Ohio, 45229, United States

Location

Mercy Hospital Anderson

Cincinnati, Ohio, 45255, United States

Location

Related Publications (1)

• Wiles JR, Isemann B, Mizuno T, Tabangin ME, Ward LP, Akinbi H, Vinks AA. Pharmacokinetics of Oral Methadone in the Treatment of Neonatal Abstinence Syndrome: A Pilot Study. J Pediatr. 2015 Dec;167(6):1214-20.e3. doi: 10.1016/j.jpeds.2015.08.032. Epub 2015 Sep 11.

  PMID: 26364984 DERIVED

MeSH Terms

Conditions

Neonatal Abstinence Syndrome

Interventions

Methadone

Condition Hierarchy (Ancestors)

Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Ketones; Organic Chemicals

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Neonatology Fellow

Study Record Dates

• First Submitted: December 14, 2012
• First Posted: December 21, 2012
• Study Start: December 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: June 13, 2014

Record last verified: 2014-06

Locations

US (2)