xml: <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/NCT06018012</url>
    </required_header>
    <id_info>
      <org_study_id>MRS&amp; ABR in jaundiced neonates</org_study_id>
      <nct_id>NCT06018012</nct_id>
    </id_info>
    <brief_title>MRA and ABR as Early Predictors of Bilirubin-Induced Neurologic Dysfunction in Full-term Jaundiced Neonates</brief_title>
    <official_title>Magnetic Resonance Spectroscopy and Auditory Brain- Stem Response Audiometry as Early Predictors of Bilirubin-Induced Neurologic Dysfunction in Full-term Jaundiced Neonates</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Tanta University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Tanta University</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The aim of the research was to define the role of MRS and ABR as early predictors of&#xD;
        bilirubin-induced neurologic dysfunction (BIND) in full-term neonates who required&#xD;
        intervention (phototherapy or exchange transfusion).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Neonatal jaundice is a prevalent condition. It's typically a harmless phase that occurs as&#xD;
        the body adjusts to bilirubin levels after birth, representing a balance between its&#xD;
        production and elimination. When there's an increase in bilirubin production and a decrease&#xD;
        in elimination, infants become at risk for dangerous hyperbilirubinemia, potentially leading&#xD;
        to bilirubin encephalopathy.&#xD;
  &#xD;
        The range of neurological issues caused by excessive bilirubin is referred to as&#xD;
        bilirubin-induced neurologic dysfunction. Detecting this condition early is crucial to&#xD;
        prevent irreversible brain damage. Some of the neurological effects include gliosis,&#xD;
        demyelination, and interference with glutamate uptake by astrocytes in the basal ganglia.&#xD;
        Magnetic resonance spectroscopy (MRS) is an advanced imaging technique that holds promise for&#xD;
        identifying these metabolic changes and aiding in the diagnosis and evaluation of neonates&#xD;
        with hyperbilirubinemia.&#xD;
  &#xD;
        Bilirubin neurotoxicity particularly affects the auditory system, starting with the brainstem&#xD;
        cochlear nuclei, followed by the auditory nerve. This damage can occur even without the&#xD;
        classic signs of bilirubin encephalopathy and is known as auditory neuropathy spectrum&#xD;
        disorder (ANSD). ANSD is characterized by abnormal auditory neural function, while cochlear&#xD;
        microphonics and otoacoustic emissions remain normal.&#xD;
  &#xD;
        The impact on hearing can vary from subtle issues in sound processing to complete deafness.&#xD;
        Abnormal results in auditory brainstem response (ABR) tests can indicate the presence of&#xD;
        acute bilirubin encephalopathy (ABE), serving as the most common and earliest sign of ABE.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Completed</overall_status>
    <start_date type="Actual">March 1, 2019</start_date>
    <completion_date type="Actual">April 1, 2021</completion_date>
    <primary_completion_date type="Actual">March 1, 2021</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Retrospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Early detection of neurological abnormalities using MRS metabolic ratios in high-risk neonates without oblivious clinical signs</measure>
      <time_frame>2 years</time_frame>
      <description>Early detection of neurological abnormalities in high-risk neonates, without oblivious clinical signs, chemically by using MRS metabolic ratio ( low NAA/Cr, NAA/Cho ratios, and high Lac/Cr ratio).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Early detection of neurological abnormalities using ABR parameters in high-risk neonates without oblivious clinical signs</measure>
      <time_frame>2 years</time_frame>
      <description>Early detection of neurological abnormalities in high-risk neonates, without oblivious clinical signs, functionally through ABR parameters ( prolonged wave III peak latency, wave V peak latency, I-III interpeak interval, and I-V interpeak interval )</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Bilirubin level and auditory abnormality</measure>
      <time_frame>2 years</time_frame>
      <description>Finding out the lowest level of total serum bilirubin at which auditory pathway abnormality was found, in comparison to age.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Bilirubin level and MRS abnormality</measure>
      <time_frame>2 years</time_frame>
      <description>Finding out the lowest level of total serum bilirubin at which MRS abnormalities were found, in comparison to age.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Discriminative capacity of MRS for acute bilirubin encephalopathy</measure>
      <time_frame>2 years</time_frame>
      <description>Determining the discriminative capacity of MRS metabolic ratios (NAA/Cr and NAA/Cho) for neonates with acute bilirubin encephalopathy and those without it with identification of the cutoff value those ratios at which acute bilirubin encephalopathy is present.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Discriminative capacity of ABR for acute bilirubin encephalopathy</measure>
      <time_frame>2 years</time_frame>
      <description>Determining the discriminative capacity of ABR wave latencies and interpeak intervals abnormalities for neonates with acute bilirubin encephalopathy and those without it with identification of the cutoff value those latencies and intervals at which acute bilirubin encephalopathy is present.</description>
    </secondary_outcome>
    <number_of_groups>3</number_of_groups>
    <enrollment type="Actual">76</enrollment>
    <condition>Neonatal Hyperbilirubinemia</condition>
    <arm_group>
      <arm_group_label>1 or acute bilirubin encephalopathy</arm_group_label>
      <description>Group (1): included 26 cases with BIND or acute bilirubin encephalopathy (ABE).</description>
    </arm_group>
    <arm_group>
      <arm_group_label>2 or neonatal hyperbilirubinemia</arm_group_label>
      <description>Group (2): included 30 cases with neonatal hyperbilirubinemia on</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control</arm_group_label>
      <description>control group: 20 healthy, age-matched neonates</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>MRS and ABR</intervention_name>
      <description>Magnetic Resonance Spectroscopy and Auditory Brain- stem Response Audiometry</description>
      <arm_group_label>1 or acute bilirubin encephalopathy</arm_group_label>
      <arm_group_label>2 or neonatal hyperbilirubinemia</arm_group_label>
      <arm_group_label>Control</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          This study included term, appropriate for gestational age (AGA) neonates with pathological&#xD;
          unconjugated hyperbilirubinemia who were candidates for intervention (Intensive&#xD;
          phototherapy versus Exchange transfusion) using the American Academy of Pediatrics&#xD;
          guidelines; 2004. In addition, 20 healthy, age-matched neonates were included as controls.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  This study included term, appropriate for gestational age (AGA) neonates with&#xD;
               pathological unconjugated hyperbilirubinemia who were candidates for intervention&#xD;
               (Intensive phototherapy versus Exchange transfusion) using the American Academy of&#xD;
               Pediatrics guidelines; 2004.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Preterm neonates (less than 37 weeks).&#xD;
  &#xD;
            2. Clinically moderate and severe acute bilirubin encephalopathy according to modified&#xD;
               Bilirubin-induced neurologic dysfunction (BIND-M) score.&#xD;
  &#xD;
            3. Neonates born with birth asphyxia and/or poor Apgar score.&#xD;
  &#xD;
            4. Neonates with sepsis including CNS infection.&#xD;
  &#xD;
            5. Neonates with family history of childhood hearing loss.&#xD;
  &#xD;
            6. Congenital infection.&#xD;
  &#xD;
            7. Chromosomal abnormalities.&#xD;
  &#xD;
            8. Congenital ear anomalies associated with hearing loss or brain abnormalities including&#xD;
               craniofacial anomalies.&#xD;
  &#xD;
            9. Patients who were receiving ototoxic drugs as aminoglycosides.&#xD;
  &#xD;
           10. Conjugated hyperbilirubinemia.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>1 Day</minimum_age>
      <maximum_age>28 Days</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>faculty of medicine,Tanta University</name>
        <address>
          <city>Tanta</city>
          <state>Q2x2+cp Tanta 2</state>
          <zip>31527</zip>
          <country>Egypt</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Egypt</country>
    </location_countries>
    <reference>
      <citation>Watchko JF, Tiribelli C. Bilirubin-induced neurologic damage--mechanisms and management approaches. N Engl J Med. 2013 Nov 21;369(21):2021-30. doi: 10.1056/NEJMra1308124. No abstract available.</citation>
      <PMID>24256380</PMID>
    </reference>
    <reference>
      <citation>Usman, F., Diala, U., Shapiro, S., Le Pichon, J.-B., &amp; Slusher, T. Acute bilirubin encephalopathy and its progression to kernicterus: current perspectives. Research and Reports in Neonatology, 8, 33-44 (2018).</citation>
    </reference>
    <reference>
      <citation>Watchko JF. Bilirubin-Induced Neurotoxicity in the Preterm Neonate. Clin Perinatol. 2016 Jun;43(2):297-311. doi: 10.1016/j.clp.2016.01.007. Epub 2016 Mar 2.</citation>
      <PMID>27235209</PMID>
    </reference>
    <reference>
      <citation>Das S, van Landeghem FKH. Clinicopathological Spectrum of Bilirubin Encephalopathy/Kernicterus. Diagnostics (Basel). 2019 Feb 28;9(1):24. doi: 10.3390/diagnostics9010024.</citation>
      <PMID>30823396</PMID>
    </reference>
    <reference>
      <citation>Teixeira MH, Borges VMS, Riesgo RDS, Sleifer P. Hyperbilirubinemia impact on newborn hearing: a literature review. Rev Assoc Med Bras (1992). 2020 Jul;66(7):1002-1008. doi: 10.1590/1806-9282.66.7.1002. Epub 2020 Aug 24.</citation>
      <PMID>32844928</PMID>
    </reference>
    <reference>
      <citation>Olds C, Oghalai JS. Audiologic impairment associated with bilirubin-induced neurologic damage. Semin Fetal Neonatal Med. 2015 Feb;20(1):42-46. doi: 10.1016/j.siny.2014.12.006. Epub 2015 Jan 7.</citation>
      <PMID>25575899</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 18, 2023</study_first_submitted>
    <study_first_submitted_qc>August 23, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 30, 2023</study_first_posted>
    <last_update_submitted>August 29, 2023</last_update_submitted>
    <last_update_submitted_qc>August 29, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Tanta University</investigator_affiliation>
      <investigator_full_name>Lamiaa Khaled Zidan</investigator_full_name>
      <investigator_title>Assistant lecturer</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Neurologic Manifestations</mesh_term>
      <mesh_term>Hyperbilirubinemia, Neonatal</mesh_term>
      <mesh_term>Hyperbilirubinemia</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06018012
  org study id: MRS& ABR in jaundiced neonates
  nct id: NCT06018012
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  The aim of the research was to define the role of MRS and ABR as early predictors of
        bilirubin-induced neurologic dysfunction (BIND) in full-term neonates who required
        intervention (phototherapy or exchange transfusion).
  Neonatal jaundice is a prevalent condition. It's typically a harmless phase that occurs as
        the body adjusts to bilirubin levels after birth, representing a balance between its
        production and elimination. When there's an increase in bilirubin production and a decrease
        in elimination, infants become at risk for dangerous hyperbilirubinemia, potentially leading
        to bilirubin encephalopathy.
  
        The range of neurological issues caused by excessive bilirubin is referred to as
        bilirubin-induced neurologic dysfunction. Detecting this condition early is crucial to
        prevent irreversible brain damage. Some of the neurological effects include gliosis,
        demyelination, and interference with glutamate uptake by astrocytes in the basal ganglia.
        Magnetic resonance spectroscopy (MRS) is an advanced imaging technique that holds promise for
        identifying these metabolic changes and aiding in the diagnosis and evaluation of neonates
        with hyperbilirubinemia.
  
        Bilirubin neurotoxicity particularly affects the auditory system, starting with the brainstem
        cochlear nuclei, followed by the auditory nerve. This damage can occur even without the
        classic signs of bilirubin encephalopathy and is known as auditory neuropathy spectrum
        disorder (ANSD). ANSD is characterized by abnormal auditory neural function, while cochlear
        microphonics and otoacoustic emissions remain normal.
  
        The impact on hearing can vary from subtle issues in sound processing to complete deafness.
        Abnormal results in auditory brainstem response (ABR) tests can indicate the presence of
        acute bilirubin encephalopathy (ABE), serving as the most common and earliest sign of ABE.
  observational model: Cohort
  time perspective: Retrospective
  measure: Early detection of neurological abnormalities using MRS metabolic ratios in high-risk neonates without oblivious clinical signs
  time frame: 2 years
  description: Early detection of neurological abnormalities in high-risk neonates, without oblivious clinical signs, chemically by using MRS metabolic ratio ( low NAA/Cr, NAA/Cho ratios, and high Lac/Cr ratio).
  measure: Early detection of neurological abnormalities using ABR parameters in high-risk neonates without oblivious clinical signs
  time frame: 2 years
  description: Early detection of neurological abnormalities in high-risk neonates, without oblivious clinical signs, functionally through ABR parameters ( prolonged wave III peak latency, wave V peak latency, I-III interpeak interval, and I-V interpeak interval )
  measure: Bilirubin level and auditory abnormality
  time frame: 2 years
  description: Finding out the lowest level of total serum bilirubin at which auditory pathway abnormality was found, in comparison to age.
  measure: Bilirubin level and MRS abnormality
  time frame: 2 years
  description: Finding out the lowest level of total serum bilirubin at which MRS abnormalities were found, in comparison to age.
  measure: Discriminative capacity of MRS for acute bilirubin encephalopathy
  time frame: 2 years
  description: Determining the discriminative capacity of MRS metabolic ratios (NAA/Cr and NAA/Cho) for neonates with acute bilirubin encephalopathy and those without it with identification of the cutoff value those ratios at which acute bilirubin encephalopathy is present.
  measure: Discriminative capacity of ABR for acute bilirubin encephalopathy
  time frame: 2 years
  description: Determining the discriminative capacity of ABR wave latencies and interpeak intervals abnormalities for neonates with acute bilirubin encephalopathy and those without it with identification of the cutoff value those latencies and intervals at which acute bilirubin encephalopathy is present.
  arm group label: 1 or acute bilirubin encephalopathy
  description: Group (1): included 26 cases with BIND or acute bilirubin encephalopathy (ABE).
  arm group label: 2 or neonatal hyperbilirubinemia
  description: Group (2): included 30 cases with neonatal hyperbilirubinemia on
  arm group label: Control
  description: control group: 20 healthy, age-matched neonates
  intervention type: Device
  intervention name: MRS and ABR
  description: Magnetic Resonance Spectroscopy and Auditory Brain- stem Response Audiometry
  arm group label: 1 or acute bilirubin encephalopathy
  arm group label: 2 or neonatal hyperbilirubinemia
  arm group label: Control
  study pop: 
  sampling method: Probability Sample
  criteria: 
  gender: All
  minimum age: 1 Day
  maximum age: 28 Days
  healthy volunteers: Accepts Healthy Volunteers
  facility: 
  country: Egypt
  citation: Watchko JF, Tiribelli C. Bilirubin-induced neurologic damage--mechanisms and management approaches. N Engl J Med. 2013 Nov 21;369(21):2021-30. doi: 10.1056/NEJMra1308124. No abstract available.
  PMID: 24256380
  citation: Usman, F., Diala, U., Shapiro, S., Le Pichon, J.-B., & Slusher, T. Acute bilirubin encephalopathy and its progression to kernicterus: current perspectives. Research and Reports in Neonatology, 8, 33-44 (2018).
  citation: Watchko JF. Bilirubin-Induced Neurotoxicity in the Preterm Neonate. Clin Perinatol. 2016 Jun;43(2):297-311. doi: 10.1016/j.clp.2016.01.007. Epub 2016 Mar 2.
  PMID: 27235209
  citation: Das S, van Landeghem FKH. Clinicopathological Spectrum of Bilirubin Encephalopathy/Kernicterus. Diagnostics (Basel). 2019 Feb 28;9(1):24. doi: 10.3390/diagnostics9010024.
  PMID: 30823396
  citation: Teixeira MH, Borges VMS, Riesgo RDS, Sleifer P. Hyperbilirubinemia impact on newborn hearing: a literature review. Rev Assoc Med Bras (1992). 2020 Jul;66(7):1002-1008. doi: 10.1590/1806-9282.66.7.1002. Epub 2020 Aug 24.
  PMID: 32844928
  citation: Olds C, Oghalai JS. Audiologic impairment associated with bilirubin-induced neurologic damage. Semin Fetal Neonatal Med. 2015 Feb;20(1):42-46. doi: 10.1016/j.siny.2014.12.006. Epub 2015 Jan 7.
  PMID: 25575899
  responsible party type: Principal Investigator
  investigator affiliation: Tanta University
  investigator full name: Lamiaa Khaled Zidan
  investigator title: Assistant lecturer
  mesh term: Neurologic Manifestations
  mesh term: Hyperbilirubinemia, Neonatal
  mesh term: Hyperbilirubinemia