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Pharmacokinetics of Multiple Dose Methadone in Children Treated for Opiate Withdrawal (MTH01)

This study has been completed.
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Phillip Brian Smith, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT01945736
First received: September 16, 2013
Last updated: March 4, 2015
Last verified: March 2015
  Purpose

The purpose of this study is to learn more about how the study drug, methadone, prescribed by an infant's or child's physician as part of standard medical care, is processed in children and young adults. While this drug is used extensively in infants and children, it has not been extensively studied in this population.

Physicians do not have very much information on how long it takes for methadone to be removed from the blood circulation and passed out of the body. Physicians need more information to guide how much and how often we should give methadone to children/young adults to ensure they get the maximum effect with the minimum amount of drug. During this research study, the study team will collect information about how this drug is processed in infants and children.


Condition Intervention Phase
Opiate Withdrawal Syndrome Drug: Methadone Phase 1

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Pharmacokinetics of Multiple Dose Methadone in Children

Resource links provided by NLM:


Further study details as provided by Phillip Brian Smith, Duke University Medical Center:

Primary Outcome Measures:
  • PK Parameters after multiple doses of enteral methadone [ Time Frame: Maximum of 7 PK samples based on dosing schedule collected over a 5 day period ]
    • Apparent oral clearance
    • Apparent oral volume of distribution
    • Area under the curve
    • Absorption rate constant


Secondary Outcome Measures:
  • PK of methadone's primary metabolite EDDP [ Time Frame: Maximum of 7 PK samples based on dosing schedule collected over a 5 day period ]
  • PK of R- and S-enantiomers of methadone [ Time Frame: Maximum of 7 PK samples based on dosing schedule collectes over a 5 day period ]
  • Correlation between plasma and DBS samples [ Time Frame: Maximum of 7 PK samples based on dosing schedule collected over a 5 day period ]
  • Correlation between plasma and scavenge samples [ Time Frame: Maximum of 7 PK samples based on dosing schedule collected over a 5 day period ]
  • Influence of CYP3A4 and CYP3B6 genetic polymorphisms on methadone PK [ Time Frame: Maximum of 7 PK samples based on dosing schedule collected over a 5 day period ]
  • Methadone pharmacodynamics using the WAT-1 [ Time Frame: Maximum of 7 PK samples based on dosing schedule collected over a 5 day period ]
  • Adverse events [ Time Frame: Study days 1-5 and observational days 6-10 ]

Biospecimen Retention:   Samples With DNA

The Study team is interested in learning more about how genetic differences in proteins known as cytochrome P450 enzymes effect the breakdown of methadone. The study team will gather leftover blood collected from the infant or child while the infant/child was in this study and send it to a laboratory to test for genetics. There will be no extra blood draws for this part of the study.

The samples for genetic testing will be given a code number and will not be labeled with the infant or child's name or initials, or any other information that could identify the infant or child. Any remaining blood will be destroyed after the genetic laboratory testing is complete.


Enrollment: 26
Study Start Date: January 2014
Study Completion Date: February 2015
Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Cohort 1
> or = 90 days to < 2 years on enteral methadone. Dose schedule is per routine medical care.
Drug: Methadone
To determine the PK of enteral methadone in children > or = 90 days and <18 years treated for opiate withdrawal per routine medical care.
Cohort 2
2 years to < 6 years on enteral methadone. Dose schedule is per routine medical care. Will include overweight children with BMI for age of 85 - 95 percentile, or obese children BMI for age > or = to 95 percentile.
Drug: Methadone
To determine the PK of enteral methadone in children > or = 90 days and <18 years treated for opiate withdrawal per routine medical care.
Cohort 3
6 years to < 18 years on enteral methadone. Dose schedule is per routine medical care. Will include overweight children with BMI for age of 85 - 95 percentile, or obese children BMI for age > or = to 95 percentile.
Drug: Methadone
To determine the PK of enteral methadone in children > or = 90 days and <18 years treated for opiate withdrawal per routine medical care.

Detailed Description:

A total of approximately 24 to 36 infants and children will participate in this study. This study will be done at five medical centers in the United States.

Treatment will be prescribed by the infant or child's doctor and not by the study team.

Participants will be divided into 3 groups based on age, ages 3 months to 2 years, ages 2 to 6 years, and ages 6 to 18 years. There will be approximately 8 to 12 participants enrolled in each group. Additionally, at least 6 overweight or obese participants between ages 2-18 years will be included in this study.

Information collected from each subject's routine medical care will include:

  • Participant gender, date of birth, race and ethnicity
  • Pertinent medical history
  • Laboratory results (blood count and chemistries) from routine testing ordered by the infant or child's regular doctor
  • Medications of interest the child was given within the 72 hours prior to first dose of methadone administered after consent
  • Time and dose of methadone administered to the child up to 14 days prior to enrollment

Study specific information collected will include:

  • Blood sample collection to measure level of methadone
  • Baseline WAT-1 score (sedation withdrawal assessment of the infant or child used to assess symptoms the child/infant may experience when opioid drugs are discontinued).

The duration of the study will be up to 10 days, comprised of a maximum 5 day treatment period a 5 day observation period.

  Eligibility

Ages Eligible for Study:   91 Days to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Participants will be divided into 3 groups based on age, ages 3 months to 2 years, ages 2 to 6 years, and ages 6 to 18 years. There will be approximately 8 to 12 participants enrolled in each group. Additionally, at least 6 overweight or obese participants between ages 2-18 years will be included in this study.
Criteria

Inclusion Criteria:

  • >90 days - < 18 years of age at the time of first dose of study drug
  • Receiving enteral methadone as standard of care
  • Signed informed consent/HIPAA documents by the parent/legal guardian and assent (if applicable)

Exclusion Criteria:

  • Previous participation in the study
  • Subject is receiving ECLS (Extracorporeal Life Support)
  • < 36 weeks gestational age at birth for children <1 year of age at time of enrollment
  • Any other condition or chronic illness that in the opinion of the Principal
  • Investigator makes participation unadvised or unsafe
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01945736

Locations
United States, Florida
All Children's Hospital
St. Petersburg, Florida, United States, 33701
United States, Kansas
Children's Mercy Hospital
Kansas City, Kansas, United States, 64108
United States, Michigan
C.S. Mott Children's Hospital
Ann Arbor, Michigan, United States, 48109
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27701
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Sponsors and Collaborators
Phillip Brian Smith
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Principal Investigator: P. Brian Smith, MD, MHS, MPH Duke Medical Center/Duke Clinical Research Institute
  More Information

Responsible Party: Phillip Brian Smith, Associate Professor of Pediatrics, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT01945736     History of Changes
Other Study ID Numbers: Pro00044082
HHSN27500021 ( Other Identifier: NICHD )
Study First Received: September 16, 2013
Last Updated: March 4, 2015

Keywords provided by Phillip Brian Smith, Duke University Medical Center:
Opiate withdrawal in children

Additional relevant MeSH terms:
Substance Withdrawal Syndrome
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

ClinicalTrials.gov processed this record on June 26, 2017