<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03291847</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00093171</org_study_id>
    <secondary_id>1R01DA041367-01A1</secondary_id>
    <nct_id>NCT03291847</nct_id>
  </id_info>
  <brief_title>Maternal Buprenorphine-naloxone Treatment and the Infant</brief_title>
  <official_title>Maternal Buprenorphine-naloxone Treatment During the Perinatal Period: Fetal and Infant Effects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Drug Abuse (NIDA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Johns Hopkins University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this mechanistic study is to evaluate the effects that maternal&#xD;
      buprenorphine-naloxone maintenance have on the neurobehavioral development of the fetus and&#xD;
      infant. To accomplish this, the investigators will study a sample of 120 opioid dependent&#xD;
      pregnant women that will receive buprenorphine-naloxone as part of substance abuse treatment&#xD;
      at a comprehensive care treatment facility for pregnant and parenting women with substance&#xD;
      use disorders. Fetal neurobehavior and maternal physiology will be assessed, via an&#xD;
      established maternal-fetal data acquisition system, at 4 points during gestation: 24, 28, 32&#xD;
      and 36 weeks. Infant birth parameters and Neonatal Abstinence Syndrome (NAS) spectrum display&#xD;
      will be evaluated at birth, and infant neurodevelopment will be assessed during the first&#xD;
      month of life. The investigators will compare the neurodevelopment of the&#xD;
      buprenorphine-naloxone-exposed fetuses and infants to that of methadone and&#xD;
      buprenorphine-only exposed fetuses and infants.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The project population will be 80 pregnant women with opioid use disorder, 40 inducted as&#xD;
      outpatients to buprenorphine-naloxone maintenance, and 40 matched methadone controls. Subject&#xD;
      treatment data, including medical and obstetric histories, drug use histories, demographic&#xD;
      information and psychosocial information will be extracted from patient charts. Weekly urine&#xD;
      toxicology testing will provide information regarding other substance use/misuse during the&#xD;
      time of study participation. Study participants will undergo 2 60 minute maternal and fetal&#xD;
      neurophysiologic monitoring sessions on one day at 4 points during gestation: 24, 28, 32 and&#xD;
      36 weeks, at times of trough (just before sublingual buprenorphine-naloxone or methadone&#xD;
      daily dose) and peak (2 1/2 hours after dosing) maternal drug levels. Fetal cardiac (heart&#xD;
      rate, heart rate variability, heart rate accelerations) and movement (total fetal movement,&#xD;
      number and duration of movement bouts) and the correlation between the two (fetal heart&#xD;
      rate-movement coupling) will be determined. Maternal physiologic measures will include heart&#xD;
      period and variability, vagal tone, skin conductance and respiratory data. All maternal and&#xD;
      fetal measures, with the exception of blood pressure, will be computed in 1-minute intervals&#xD;
      and averaged over the 60 min recording. Infant birth data and birth parameters, and neonatal&#xD;
      abstinence syndrome scores will be extracted from patient charts. Infants will undergo&#xD;
      neurobehavioral testing using the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral&#xD;
      Scale, a 30 minute harmless assessment of infant functioning, on days 3, 14 and 30 of life.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 1, 2018</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Actual">December 27, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>One group of n=40 study participants will receive buprenorphine-naloxone medication assisted therapy for the treatment of opioid use disorder during pregnancy, a second group of n=40 will receive methadone as standard of care. Subjects will undergo identical study procedures.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Fetal Heart Rate (FHR) 24</measure>
    <time_frame>24 weeks of gestation</time_frame>
    <description>Fetal heart rate in msec, mean over 60 minutes gestation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>FHR28</measure>
    <time_frame>28 weeks of gestation</time_frame>
    <description>Fetal heart rate in msec, mean over 60 minutes gestation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>FHR32</measure>
    <time_frame>32 weeks of gestation</time_frame>
    <description>Fetal heart rate in msec, mean over 60 minutes</description>
  </primary_outcome>
  <primary_outcome>
    <measure>FHR36</measure>
    <time_frame>36 weeks of gestation</time_frame>
    <description>Fetal heart rate in msec, mean over 60 minutes</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Neonatal abstinence syndrome severity score (NAS)1</measure>
    <time_frame>day 1 of life</time_frame>
    <description>NAS lists 21 symptoms most frequently observed in opiate-exposed infants. Baseline score is recorded two hours after birth or admission to the nursery. If the infant's score at any scoring interval is ≥ 8, scoring is increased to 2-hourly and continued for 24 hours from the last total score of 8 or higher. If the 2-hourly score is ≤ 7 for 24 hours then 4-hourly scoring intervals may be resumed. If pharmacotherapy is not needed the infant is scored for the first 4 days of life at 4-hourly intervals. If pharmacotherapy is required the infant is scored at 2- or 4-hourly intervals, depending on whether the abstinence score is less than or greater than 8 throughout the duration of therapeutic period. If after cessation of pharmacotherapy the score is less than 8 for the following 3 days, scoring may be discontinued.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NAS2</measure>
    <time_frame>day 2 of life</time_frame>
    <description>Neonatal abstinence syndrome severity score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NAS3</measure>
    <time_frame>day 3 of life</time_frame>
    <description>Neonatal abstinence syndrome severity score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NAS4</measure>
    <time_frame>day 4 of life</time_frame>
    <description>Neonatal abstinence syndrome severity score</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Maternal Opioid Use Disorder</condition>
  <condition>Opioid Exposed Infant</condition>
  <arm_group>
    <arm_group_label>Buprenorphine-naloxone treated</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receiving buprenorphine-naloxone treatment for opioid use disorder during pregnancy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Methadone treated</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants receiving methadone treatment for opioid use disorder during pregnancy</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>fetal monitoring</intervention_name>
    <description>Maternal fetal monitoring</description>
    <arm_group_label>Buprenorphine-naloxone treated</arm_group_label>
    <arm_group_label>Methadone treated</arm_group_label>
    <other_name>maternal physiology monitoring</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Buprenorphine Naloxone</intervention_name>
    <description>Treatment for opioid use disorder</description>
    <arm_group_label>Buprenorphine-naloxone treated</arm_group_label>
    <other_name>Suboxone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methadone</intervention_name>
    <description>Treatment for opioid use disorder</description>
    <arm_group_label>Methadone treated</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Current opioid use disorder (OUD) as defined by DSM V criteria&#xD;
&#xD;
          -  singleton pregnancies, generally uncomplicated by conditions that jeopardize pregnancy&#xD;
             outcome&#xD;
&#xD;
          -  Gestation less than 24 weeks&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Complications of pregnancy, including gestational diabetes, polyhydramnios,&#xD;
             hypertension, placenta previa or significant risk of preterm delivery;&#xD;
&#xD;
          -  Evidence of fetal malformation detected by prenatal ultrasound;&#xD;
&#xD;
          -  Significant general maternal health problems that can affect fetal functioning,&#xD;
             including Type I or gestational diabetes, alterations in thyroid functioning, HIV&#xD;
             infection or hypertension;&#xD;
&#xD;
          -  Significant maternal psychopathology that would preclude informed consent;&#xD;
&#xD;
          -  Alcohol use disorder per DSM V criteria (see ascertainment methods below)&#xD;
&#xD;
          -  Women stable on methadone maintenance (defined as more than 3 consecutive days of&#xD;
             dosing)&#xD;
&#xD;
          -  Women coming to treatment reporting &quot;street&quot; methadone use (for more than 3&#xD;
             consecutive days&#xD;
&#xD;
          -  Women not planning to receive obstetric care at the Center for Addiction and&#xD;
             Pregnancy; - Women not planning to deliver their infants at Johns Hopkins Bayview&#xD;
             Medical center&#xD;
&#xD;
          -  Women planning for adoption of their infant.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Pregnant women with opioid use disorder</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>44 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lauren M Jansson, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Johns Hopkins Bayview Medical Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>September 14, 2017</study_first_submitted>
  <study_first_submitted_qc>September 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <last_update_submitted>August 17, 2023</last_update_submitted>
  <last_update_submitted_qc>August 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>maternal opioid use</keyword>
  <keyword>neonatal abstinence syndrome</keyword>
  <keyword>buprenorphine-naloxone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Opioid-Related Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Buprenorphine</mesh_term>
    <mesh_term>Methadone</mesh_term>
    <mesh_term>Buprenorphine, Naloxone Drug Combination</mesh_term>
    <mesh_term>Naloxone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03291847
org study id: IRB00093171
secondary id: 1R01DA041367-01A1
nct id: NCT03291847
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this mechanistic study is to evaluate the effects that maternal
      buprenorphine-naloxone maintenance have on the neurobehavioral development of the fetus and
      infant. To accomplish this, the investigators will study a sample of 120 opioid dependent
      pregnant women that will receive buprenorphine-naloxone as part of substance abuse treatment
      at a comprehensive care treatment facility for pregnant and parenting women with substance
      use disorders. Fetal neurobehavior and maternal physiology will be assessed, via an
      established maternal-fetal data acquisition system, at 4 points during gestation: 24, 28, 32
      and 36 weeks. Infant birth parameters and Neonatal Abstinence Syndrome (NAS) spectrum display
      will be evaluated at birth, and infant neurodevelopment will be assessed during the first
      month of life. The investigators will compare the neurodevelopment of the
      buprenorphine-naloxone-exposed fetuses and infants to that of methadone and
      buprenorphine-only exposed fetuses and infants.
The project population will be 80 pregnant women with opioid use disorder, 40 inducted as
      outpatients to buprenorphine-naloxone maintenance, and 40 matched methadone controls. Subject
      treatment data, including medical and obstetric histories, drug use histories, demographic
      information and psychosocial information will be extracted from patient charts. Weekly urine
      toxicology testing will provide information regarding other substance use/misuse during the
      time of study participation. Study participants will undergo 2 60 minute maternal and fetal
      neurophysiologic monitoring sessions on one day at 4 points during gestation: 24, 28, 32 and
      36 weeks, at times of trough (just before sublingual buprenorphine-naloxone or methadone
      daily dose) and peak (2 1/2 hours after dosing) maternal drug levels. Fetal cardiac (heart
      rate, heart rate variability, heart rate accelerations) and movement (total fetal movement,
      number and duration of movement bouts) and the correlation between the two (fetal heart
      rate-movement coupling) will be determined. Maternal physiologic measures will include heart
      period and variability, vagal tone, skin conductance and respiratory data. All maternal and
      fetal measures, with the exception of blood pressure, will be computed in 1-minute intervals
      and averaged over the 60 min recording. Infant birth data and birth parameters, and neonatal
      abstinence syndrome scores will be extracted from patient charts. Infants will undergo
      neurobehavioral testing using the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral
      Scale, a 30 minute harmless assessment of infant functioning, on days 3, 14 and 30 of life.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: One group of n=40 study participants will receive buprenorphine-naloxone medication assisted therapy for the treatment of opioid use disorder during pregnancy, a second group of n=40 will receive methadone as standard of care. Subjects will undergo identical study procedures.
primary purpose: Basic Science
masking: None (Open Label)
measure: Fetal Heart Rate (FHR) 24
time frame: 24 weeks of gestation
description: Fetal heart rate in msec, mean over 60 minutes gestation
measure: FHR28
time frame: 28 weeks of gestation
description: Fetal heart rate in msec, mean over 60 minutes gestation
measure: FHR32
time frame: 32 weeks of gestation
description: Fetal heart rate in msec, mean over 60 minutes
measure: FHR36
time frame: 36 weeks of gestation
description: Fetal heart rate in msec, mean over 60 minutes
measure: Neonatal abstinence syndrome severity score (NAS)1
time frame: day 1 of life
description: NAS lists 21 symptoms most frequently observed in opiate-exposed infants. Baseline score is recorded two hours after birth or admission to the nursery. If the infant's score at any scoring interval is ≥ 8, scoring is increased to 2-hourly and continued for 24 hours from the last total score of 8 or higher. If the 2-hourly score is ≤ 7 for 24 hours then 4-hourly scoring intervals may be resumed. If pharmacotherapy is not needed the infant is scored for the first 4 days of life at 4-hourly intervals. If pharmacotherapy is required the infant is scored at 2- or 4-hourly intervals, depending on whether the abstinence score is less than or greater than 8 throughout the duration of therapeutic period. If after cessation of pharmacotherapy the score is less than 8 for the following 3 days, scoring may be discontinued.
measure: NAS2
time frame: day 2 of life
description: Neonatal abstinence syndrome severity score
measure: NAS3
time frame: day 3 of life
description: Neonatal abstinence syndrome severity score
measure: NAS4
time frame: day 4 of life
description: Neonatal abstinence syndrome severity score
arm group label: Buprenorphine-naloxone treated
arm group type: Experimental
description: Participants receiving buprenorphine-naloxone treatment for opioid use disorder during pregnancy
arm group label: Methadone treated
arm group type: Active Comparator
description: Participants receiving methadone treatment for opioid use disorder during pregnancy
intervention type: Device
intervention name: fetal monitoring
description: Maternal fetal monitoring
arm group label: Buprenorphine-naloxone treated
arm group label: Methadone treated
other name: maternal physiology monitoring
intervention type: Drug
intervention name: Buprenorphine Naloxone
description: Treatment for opioid use disorder
arm group label: Buprenorphine-naloxone treated
other name: Suboxone
intervention type: Drug
intervention name: Methadone
description: Treatment for opioid use disorder
arm group label: Methadone treated
criteria: 
gender: Female
gender based: Yes
gender description: Pregnant women with opioid use disorder
minimum age: 18 Years
maximum age: 44 Years
healthy volunteers: No
last name: Lauren M Jansson, MD
role: Principal Investigator
affiliation: Johns Hopkins University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Opioid-Related Disorders
mesh term: Buprenorphine
mesh term: Methadone
mesh term: Buprenorphine, Naloxone Drug Combination
mesh term: Naloxone
sharing ipd: No