Methadone Demonstration Project With Neonatal Intensive Care Unit Infants Diagnosed With Neonatal Abstinence Syndrome

This is a non-randomized, un-blinded feasibility study project comparing the Length of Stay (LOS) of Neonatal Intensive Care Unit (NICU) infants diagnosed with Neonatal Abstinence Syndrome (NAS) treated with methadone with historical data and a comparison group of NICU NAS infants treated with a different narcotic agent.

Study Overview

• Status: Terminated
• Conditions: Neonatal Abstinence Syndrome
• Intervention / Treatment: Drug: Methadone; Drug: Morphine

Detailed Description

For the time frame July 1, 2013 through September 30, 2014, 300 infants with NAS have been cared for in the JHACH NICU with an average length of stay of 30 days. Such a prolonged length of stay has a negative impact on maternal/infant bonding. In addition, infants suffering from NAS have poor regulatory mechanisms and are invariably hard to care for and difficult to console, and they provide an emotional challenge to their caretakers. This challenge becomes even more significant when the caretaker is the mother who is suffering from addiction and is already emotionally compromised by feelings of depression, anxiety, guilt or insecurity. Attachment is an ongoing process and the quality of the relationship between mother and her infant directly influences the structure of the child's affective ties and overall organization of responses to environment. This mother-infant bond sets the stage for understanding and identifying the infant's needs and reciprocal parental response to those needs. Maternal emotional unavailability has potentially serious effects on the long term mother-child relationship, and on the child's development.

This project provides a novel approach and an alternative care plan for infants with NAS. It is funded by the State of Florida and allows to: 1) educate and empower a specified population of mothers who are undergoing institutionalized rehabilitation and whose infant needs treatment for NAS; 2) safely transition the infants home for final wean of their pharmacologic treatment; 3) provide regular developmental follow up for these infants through our NICU follow up clinic, hence identifying and quickly responding to neuro-developmental delays.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Saint Petersburg, Florida, United States, 33701
      • Johns Hopkins All Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 days (Child)
• Accepts Healthy Volunteers: No

Description

Methadone Treatment Group:

Inclusion criteria:

1. Baby is diagnosed with neonatal abstinence syndrome;
2. Mother under the care of Operation PAR;
3. Mother resides in Pinellas or Pasco county at the time of enrollment and is expected to throughout the infant's methadone treatment period;
4. Mother has been deemed by PAR officials as being compliant with the detoxification program;
5. Mother has completed induction methadone treatment and has had no changes in medication dosage of 10% or greater in the two weeks preceding delivery;
6. Mother has been prescreened and deemed adequate candidate by the demonstration project team members;
7. No known concerns from Florida Department of Children and Families regarding the infant's ability to return to the home;
8. Newborns ≥ 37 0/7 weeks gestation;
9. Newborns transferred to JHACH within 72 hours from birth;
10. Newborns ≥ 2.5 kg weight at birth;
11. Informed parental consent.

Exclusion Criteria:

1. Major congenital anomalies;
2. Major concomitant medical illness including planned antibiotic treatment for greater than 3 days or NPO status;
3. Infants who are being placed for adoption;
4. Infants in significant pain requiring narcotic medication for comfort (for example those with a fracture);
5. Infants whose maternal UDS at the time of delivery is positive for any other drug of abuse beside opiates.
6. Mother with hearing or language impairment

Comparison Group:

Inclusion Criteria:

1. Baby is diagnosed with neonatal abstinence syndrome;
2. Newborns ≥ 37 0/7 weeks gestation;
3. Newborns transferred to JHACH within 72 hours from birth;
4. Newborns ≥ 2.5 kg weight at birth;
5. Informed parental consent.

Exclusion Criteria:

1. Infant not requiring pharmacologic treatment for NAS;
2. Major congenital anomalies;
3. Major concomitant medical illness including planned antibiotic treatment for greater than 3 days or NPO status;
4. Infants who are being placed for adoption;
5. Infants in significant pain requiring narcotic medication for comfort (for example those with a fracture);
6. Mother with hearing or language impairment;
7. Infants known upon admission who will be placed into state custody or sheltered.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Methadone Treatment Group; NAS infants treated for withdrawal symptoms with methadone	Drug: Methadone; Infants in the Methadone Treatment Group will receive the study drug, methadone, instead of morphine to treat withdrawal symptoms from Neonatal Abstinence Syndrome (NAS)
Active Comparator: Comparison Group; NAS infants treated for withdrawal symptoms with morphine (standard of care at Johns Hopkins All Children's Hospital)	Drug: Morphine; Infants in the Comparison Group will receive standard of care narcotic (morphine) to treat withdrawal symptoms from Neonatal Abstinence Syndrome (NAS)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of Stay (LOS)	Compare the LOS of Neonatal Intensive Care Unit (NICU) infants with Neonatal Abstinence Syndrome (NAS) treated with methadone with historical data and a comparison group of NICU NAS infants treated with a different narcotic agent.	25 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal Bonding Measured With The Postpartum Bonding Questionnaire (PBQ)	The Postpartum Bonding Questionnaire (PBQ) is a self-rating questionnaire designed to detect disorders of the mother-infant relationship. The questionnaire has 25 statements, each with six alternative responses ranging from 0 (always) to 5 (never). For the PBQ, scores are summated for each factor, with a high score indicating concern for bonding. The PBQ yields a total score between 0 to 125. Positive responses are scored from 0 ('always') to 5 ('never'). Negative responses, are scored from 5 ('always') to 0 ('never'). Factor 1 (impaired bonding) is based on 12 questions, with a score range 0-60 (0-11=normal; 12 & above=high). Factor 2 (rejection & anger) is based on 7 questions with a score range 0-35 (0-16=normal; 17 & above=high). Factor 3 (anxiety about care) is based on 4 questions with a score range 0-20 (0-9=normal; 10 & above =high). Factor 4 (risk of abuse) is based on 2 questions, with a score range 0-10 (0-2=normal; 3 & above =high).	inpatient and at 6-8 weeks of age
Maternal Depression Measured With The Edinburgh Postnatal Depression Scale (EPDS)	The Edinburgh Postnatal Depression Scale (EPDS) was developed for screening postpartum women in outpatient, home visiting settings, or at the 6-8 week postpartum examination. The EPDS is a 10-item questionnaire with responses scored 0, 1, 2, or 3 according to increased severity of the symptom. The maximum total score is 30 while the minimum score is 0. A score of 10 or greater, as well as any answer choice other than "never" on question #10 (suicidal thoughts) of the EPDS are indicative of depressive symptomatology.	While inpatient and at 6-8 weeks of age
Readmission to Hospital	Number of hospital readmissions	Within 30 days of discharge
Breast Milk	Compare the incidence of providing breast milk (> 50% of nutritional needs) at 30 days of age between methadone treated and non-treated infants	30 days of age
Infant Development	Assess the age appropriate infant development at 4, 8 and 12 months of age among the methadone treatment group using the Ages and Stages-based questionnaires (ASQ). The questionnaires are screening tools designed to identify infants at risk for developmental delays through caregivers' provision of quantitative information regarding their infant's development. In the ASQ, higher scores indicate more positive outcomes. The ASQ covers 5 areas of development: communication, gross motor, fine motor, problem solving, and personal-social. Scores for each area should fall between 0-60. Scoring: 0-30 = further assessment with a professional may be needed 30-40 = learning activities & monitoring are indicated 45-60 = child development appears to be on schedule	4, 8 and 12 months of age
Screened vs. Eligible	Determine the response percentage of mothers who are screened as eligible by PAR officials and who agree to participate in the demonstration project	After accrual of the first 50% of participants & after accrual of the second 50% of participants, and at completion of the trial.
Attrition Rate	Assess the drop out percentage of mothers who agree to participate but do not follow through with home discharge for continued care	After accrual of the first 50% of participants, after accrual of the second 50% of participants, and at completion of the trial.
Home Care	Quantitate the proportion of mothers who feel comfortable with home care of their infant at discharge	After accrual of the first 50% of participants, after accrual of the second 50% of participants, and at completion of the trial
Readiness of Mothers to Assess Infant	Monitor the readiness of mothers to assess infant on 3 to 4 hours intervals while at home	After accrual of the first 50% of participants, after accrual of the second 50% of participants, and at completion of the trial.
Compliance With Pediatrician Visits	Determine the compliance rate with the Johns Hopkins All Children's Hospital (JHACH) pediatrician visits.	After accrual of the first 50% of participants, after accrual of the second 50% of participants, and at completion of the trial.

Collaborators and Investigators

• Sponsor: Johns Hopkins All Children's Hospital
• Collaborators: Florida Department of Health
• Investigators: Principal Investigator: Sandra Brooks, MD, Johns Hopkins All Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2017
• Primary Completion (Actual): March 26, 2019
• Study Completion (Actual): March 27, 2019

Study Registration Dates

• First Submitted: March 3, 2017
• First Submitted That Met QC Criteria: April 26, 2017
• First Posted (Actual): May 1, 2017

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 28, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Substance-Related Disorders; Disease; Infant, Newborn, Diseases; Syndrome; Neonatal Abstinence Syndrome; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Morphine; Methadone
• Other Study ID Numbers: IRB00107690

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No