Neonatal Abstinence SyndromeNCT01754324
The Pharmacokinetics of Oral Methadone in the Treatment of Neonatal Abstinence Syndrome
An observational study of Neonatal Abstinence Syndrome, run by Children's Hospital Medical Center, Cincinnati at 2 sites in United States.
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). Read more about this study
- Who is it for?
- Ages Up to 1 month
- Conditions the study is for
- Neonatal Abstinence Syndrome
- What is being tested?
- Methadone
- Type of treatment
- Pill or oral medicine
- How many people
- 20 participants
- Where
- 2 sitesUnited States
- Study dates
- Dec 2012to Dec 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 1 month
- All sexes
- No healthy volunteers
- Child
Study population: Infants diagnosed with Neonatal Abstinence Syndrome and are treated with oral methadone.
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
The University Hospital
Cincinnati, Ohio, 45229
Mercy Hospital Anderson
Cincinnati, Ohio, 45255
About this study
Official title: The Utility and Pharmacokinetics of Oral Methadone in the Treatment of Neonatal Abstinence Syndrome in Neonates
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
- Being tested
- Methadone
- Keywords
- Neonatal Abstinence Syndrome, Pharmacokinetics, Methadone, Neonate, Newborn
- Medical subject headings
- Neonatal Abstinence Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethadoneDrug
Also called methadone hydrochloride
The starting dose of the protocol is 0.05mg/kg by mouth given every 6 hours and gradually decreased in a stepwise, standardized fashion.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Methadone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks).
Secondary outcomes (5)
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.
Measured: Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks).
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.
Measured: Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks).
Length of hospitalization
This endpoint will describe the number of days infants were hospitalized for treatment of NAS.
Measured: Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks).
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.
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.
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.
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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2012 (estimated)
- Study startDec 2012
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neonatal Abstinence SyndromeStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Jason Wiles, MD, Children's Hospital Medical Center, Cincinnati
- Investigators
- Jason R Wiles, MD, Principal investigator, Children's Hospital Medical Center, CincinnatiHenry Akinbi, MD, Principal investigator, Children's Hospital Medical Center, CincinnatiAlexander Vinks, PharmD, PhD, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01754324
- Sponsor's protocol ID
- CCHMC-PK-1
- Other IDs
- 5T32HD069054
- Status last verified
- Jun 2014
- First submitted
- 14 Dec 2012
- Last updated
- 13 Jun 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 26364984
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Utility and Pharmacokinetics of Oral Methadone in the Treatment of Neonatal Abstinence Syndrome in Neonates
- ClinicalTrials.gov ID
- NCT01754324
- Acronym / sponsor ID
- CCHMC-PK-1
- Conditions
- Neonatal Abstinence Syndrome
- Keywords
- Neonatal Abstinence Syndrome, Pharmacokinetics, Methadone, Neonate, Newborn
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Dec 2012
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 21 Dec 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Methadone | – | Drug: MethadoneAll 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. |
Who may qualify
- Ages
- Up to 1 month
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Infants diagnosed with Neonatal Abstinence Syndrome and are treated with oral methadone.
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethadoneAlso: methadone hydrochlorideThe starting dose of the protocol is 0.05mg/kg by mouth given every 6 hours and gradually decreased in a stepwise, standardized fashion. | Drug | Methadone |
Primary outcome
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.
5 secondary outcomes
Failed Protocol Wean
Time frame: Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks).
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).
Length of hospitalization
Time frame: Participants will be followed for the duration of the hospital stay (an expected average of 4 weeks).
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.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2014.
- Derived from this study: PubMed 26364984Wiles 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jason R Wiles, MD principal investigator
Children's Hospital Medical Center, Cincinnati
Henry Akinbi, MD principal investigator
Children's Hospital Medical Center, Cincinnati
Alexander Vinks, PharmD, PhD principal investigator
Children's Hospital Medical Center, Cincinnati
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Neonatal Abstinence Syndrome, run by Children's Hospital Medical Center, Cincinnati at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01754324, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jun 2014.