<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/NCT03806816</url>
  </required_header>
  <id_info>
    <org_study_id>23/2018/SPER/AOUFE</org_study_id>
    <nct_id>NCT03806816</nct_id>
  </id_info>
  <brief_title>Use of Melatonin for Neuroprotection in Asphyxiated Newborns</brief_title>
  <acronym>MELPRO</acronym>
  <official_title>Use of Melatonin for Neuroprotection in Term Infants With Hypoxic-ischaemic Encephalopathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital of Ferrara</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AUSL Romagna Rimini</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital of Ferrara</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Protection of brain development is a major aim in the Neonatal Intensive Care Unit.&#xD;
      Hypoxic-Ischemic Encephalopathy (HIE) occurs in 3-5 per 1000 births. Only 47% of neonates&#xD;
      have normal outcomes. The neurodevelopmental consequences of brain injury for asphyxiated&#xD;
      term infants include cerebral palsy, severe intellectual disabilities and also a number of&#xD;
      minor behavioural and cognitive deficits. However, there are very few therapeutic strategies&#xD;
      for the prevention or treatment of brain damage. The gold standard is hypothermic treatment&#xD;
      but, according to the literature, melatonin potentially acts in synergy with hypothermia for&#xD;
      neuroprotection and to improve neurologic outcomes. Melatonin appears to be a good candidate&#xD;
      because of its different protective effects including reactive oxygen species scavenging,&#xD;
      excitotoxic cascade blockade, modulation of neuroinflammatory pathways.&#xD;
&#xD;
      The research study will evaluate the neuroprotective properties and the effects of Melatonin&#xD;
      in association with therapeutic hypothermia for hypoxic ischemic encephalopathy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      It is a randomized double blind, placebo controlled trial on 100 neonates with moderate to&#xD;
      moderately to severe hypoxic ischemic encephalopathy (HIE) . HIE infants are randomized into&#xD;
      two groups: Whole body cooling group (N = 50 receive 72 hours of whole body hypothermia) and&#xD;
      melatonin/ hypothermia group (N = 50; receive hypothermia and 5 daily enteral doses of&#xD;
      melatonin 10 mg/kg). Serum melatonin and autophagy levels are measured at enrollment, daily&#xD;
      during the hypothermic treatment, at day 5 and 7 for the two HIE groups.&#xD;
&#xD;
      aEEG will be performed for 72 hrs during the hypothermic treatment and the re-warming. MRI&#xD;
      and Spectroscopy analysis will be performed between day 5 and 7 of. After hospital discharge&#xD;
      the infants will enter a follow-up program consisting in periodic clinical and developmental&#xD;
      assessments until 2 years of age corrected for prematurity. An expert psychologist and a&#xD;
      neonatologist will assess neurodevelopmental outcome using the Bayley Scales III at 6-12-24&#xD;
      months of corrected age.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">December 13, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Bayley III scale</measure>
    <time_frame>12 months</time_frame>
    <description>Bayley scale of infant and toddler development. It measures developmental skills reached by infant and young children between 1 month and 42 months The scale is subdivided into 5 subscales Cognitive,Receptive communication,Expressive communication,Fine motor ,Gross motor.Receptive and expressive communication have a composite in language score So as fine and gross motor in motor score For all subtests raw scores correspond to scaled scores ranging from 1 to 19 with a mean of 10 and SD of 3 The composite scores are given by the sum of the corresponding subtests scaled scores.&#xD;
Two parent-reported scales (Social-Emotional and Adaptive Behavior) will be collected.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>brain MRI</measure>
    <time_frame>between the 5th and 7th days of life</time_frame>
    <description>to evaluate the presence of deep grey matter, PLIC, white matter, brainstem and hippocampus lesions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>continuous aEEG</measure>
    <time_frame>Continuous monitoring for the first 72 hours and for the rewarmed</time_frame>
    <description>Al Naqueeb classification for aEEG will be used.Background voltage pattern will be scored in NORMAL (Lower margin &gt;5μV,Upper margin &gt;10μV The activity is continuous), MODERATELY ABORMAL (Lower margin &lt;5μV, upper margin &gt;10μV,The activity is moderately discontinuous)SEVERELY ABNORMAL/ SUPPRESSED (Lower margin &lt;5μV, upper margin &lt;10μV)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Concentration of Melatonin</measure>
    <time_frame>at birth, 24 hours, 48 hours, 72 hours, 5 days, 7 days of life</time_frame>
    <description>UPLC-Massa Acquity-Xevo TQD (Waters) will be used to measure melatonin concentrations in the plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ATG5 Plasma concentration</measure>
    <time_frame>at birth, 24 hours, 48 hours, 72 hours, 5 days, 7 days of life</time_frame>
    <description>ELISA test will be used to measure plasma levels of ATG5</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Hypoxic-Ischemic Encephalopathy</condition>
  <condition>Cell Damage</condition>
  <condition>Asphyxia Perinatal</condition>
  <arm_group>
    <arm_group_label>HYPOTHERMIA / MELATONIN group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HIE infants who will receive melatonin in addition to the routine cooling treatment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HYPOTHERMIA / PLACEBO group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HIE infants who will not receive melatonin in addition to the routine cooling treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Melatonin</intervention_name>
    <description>5 daily enteral doses of melatonin 10 mg/kg. (=2 ml/kg)</description>
    <arm_group_label>HYPOTHERMIA / MELATONIN group</arm_group_label>
    <other_name>Buona Circadiem</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>PLACEBO group</intervention_name>
    <description>5 daily enteral doses of placebo 2 ml/kg</description>
    <arm_group_label>HYPOTHERMIA / PLACEBO group</arm_group_label>
    <other_name>placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  gestational age &gt; 35 weeks and weight &gt; 1800 gr&#xD;
&#xD;
          -  Apgar score &lt; 5 at 10 minutes o need for cardiopulmonary resuscitation at 10 minutes&#xD;
             or evidence of base excess &gt; 12 mmol/L or pH &lt; 7,0 at initial blood gas analyses&#xD;
&#xD;
          -  evidence of moderate or severa encephalopathy graded according to Sarnat&amp;Sarnat&#xD;
             neurological evaluation&#xD;
&#xD;
          -  abnormal amplitude integrated electroencephalography&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  suspected inborn errors of metabolism&#xD;
&#xD;
          -  major chromosomal congenital defects&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Hour</minimum_age>
    <maximum_age>6 Hours</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anna Tarocco, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital of Ferrara</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Anna Tarocco, MD</last_name>
    <phone>+390532236014</phone>
    <email>anna.tarocco@unife.it</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Paolo Pinton, Professor</last_name>
    <phone>+390532455802</phone>
    <email>paolo.pinton@unife.it</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Ospedale Pediatrico Bambin Gesù</name>
      <address>
        <city>Vatican City</city>
        <country>Holy See (Vatican City State)</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Immacolata Savarese, MD</last_name>
    </contact>
    <contact_backup>
      <last_name>Andrea Dotta, MD</last_name>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>ospdale di Bolzano</name>
      <address>
        <city>Bolzano</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Elisabetta Chiodin, MD</last_name>
    </contact>
    <contact_backup>
      <last_name>Alex Staffler, MD</last_name>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Bufalini Hospital Cesena</name>
      <address>
        <city>Cesena</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>MARCELLO Stella</last_name>
      <email>marcello.stella@auslromagna.it</email>
    </contact>
    <contact_backup>
      <last_name>Elisa Mariani</last_name>
      <email>elisa.mariani@auslromagna.it</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>University Hospital &quot;Sant'Anna&quot; of Ferrara</name>
      <address>
        <city>Ferrara</city>
        <zip>44124</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anna Tarocco, MD</last_name>
      <phone>+390532236014</phone>
      <email>anna.tarocco@unife.it</email>
    </contact>
    <contact_backup>
      <last_name>Paolo Pinton, Prof</last_name>
      <phone>+390532455802</phone>
      <email>paolo.pinton@unife.it</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>ospedale San Salvatore</name>
      <address>
        <city>L'Aquila</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eugenia Maranella, MD</last_name>
    </contact>
    <contact_backup>
      <last_name>Sandra Di Fabio, MD</last_name>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Infermi Hospital Rimini</name>
      <address>
        <city>Rimini</city>
        <zip>47923</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gina Ancora, MD PhD</last_name>
      <phone>+390541705445</phone>
      <email>gina.ancora@auslromagna.it</email>
    </contact>
    <contact_backup>
      <last_name>Miria Natile, MD</last_name>
      <phone>+390541705445</phone>
      <email>mirianatile@gmail.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Holy See (Vatican City State)</country>
    <country>Italy</country>
  </location_countries>
  <results_reference>
    <citation>Wang Q, Lv H, Lu L, Ren P, Li L. Neonatal hypoxic-ischemic encephalopathy: emerging therapeutic strategies based on pathophysiologic phases of the injury. J Matern Fetal Neonatal Med. 2019 Nov;32(21):3685-3692. doi: 10.1080/14767058.2018.1468881. Epub 2018 May 2.</citation>
    <PMID>29681183</PMID>
  </results_reference>
  <results_reference>
    <citation>Hassell KJ, Ezzati M, Alonso-Alconada D, Hausenloy DJ, Robertson NJ. New horizons for newborn brain protection: enhancing endogenous neuroprotection. Arch Dis Child Fetal Neonatal Ed. 2015 Nov;100(6):F541-52. doi: 10.1136/archdischild-2014-306284. Epub 2015 Jun 10.</citation>
    <PMID>26063194</PMID>
  </results_reference>
  <results_reference>
    <citation>McAdams RM, Juul SE. Neonatal Encephalopathy: Update on Therapeutic Hypothermia and Other Novel Therapeutics. Clin Perinatol. 2016 Sep;43(3):485-500. doi: 10.1016/j.clp.2016.04.007. Epub 2016 Jun 22.</citation>
    <PMID>27524449</PMID>
  </results_reference>
  <results_reference>
    <citation>Ramos E, Patino P, Reiter RJ, Gil-Martin E, Marco-Contelles J, Parada E, de Los Rios C, Romero A, Egea J. Ischemic brain injury: New insights on the protective role of melatonin. Free Radic Biol Med. 2017 Mar;104:32-53. doi: 10.1016/j.freeradbiomed.2017.01.005. Epub 2017 Jan 6.</citation>
    <PMID>28065781</PMID>
  </results_reference>
  <results_reference>
    <citation>Balduini W, Carloni S, Perrone S, Bertrando S, Tataranno ML, Negro S, Proietti F, Longini M, Buonocore G. The use of melatonin in hypoxic-ischemic brain damage: an experimental study. J Matern Fetal Neonatal Med. 2012 Apr;25 Suppl 1:119-24. doi: 10.3109/14767058.2012.663232. Epub 2012 Mar 5.</citation>
    <PMID>22348528</PMID>
  </results_reference>
  <results_reference>
    <citation>Parikh P, Juul SE. Neuroprotective Strategies in Neonatal Brain Injury. J Pediatr. 2018 Jan;192:22-32. doi: 10.1016/j.jpeds.2017.08.031. Epub 2017 Oct 12. No abstract available.</citation>
    <PMID>29031859</PMID>
  </results_reference>
  <results_reference>
    <citation>Martinello K, Hart AR, Yap S, Mitra S, Robertson NJ. Management and investigation of neonatal encephalopathy: 2017 update. Arch Dis Child Fetal Neonatal Ed. 2017 Jul;102(4):F346-F358. doi: 10.1136/archdischild-2015-309639. Epub 2017 Apr 6.</citation>
    <PMID>28389438</PMID>
  </results_reference>
  <results_reference>
    <citation>Shea KL, Palanisamy A. What can you do to protect the newborn brain? Curr Opin Anaesthesiol. 2015 Jun;28(3):261-6. doi: 10.1097/ACO.0000000000000184.</citation>
    <PMID>25827279</PMID>
  </results_reference>
  <results_reference>
    <citation>Alonso-Alconada D, Alvarez A, Arteaga O, Martinez-Ibarguen A, Hilario E. Neuroprotective effect of melatonin: a novel therapy against perinatal hypoxia-ischemia. Int J Mol Sci. 2013 Apr 29;14(5):9379-95. doi: 10.3390/ijms14059379.</citation>
    <PMID>23629670</PMID>
  </results_reference>
  <results_reference>
    <citation>Fan X, van Bel F. Pharmacological neuroprotection after perinatal asphyxia. J Matern Fetal Neonatal Med. 2010 Oct;23 Suppl 3:17-9. doi: 10.3109/14767058.2010.505052.</citation>
    <PMID>20695757</PMID>
  </results_reference>
  <results_reference>
    <citation>Cilio MR, Ferriero DM. Synergistic neuroprotective therapies with hypothermia. Semin Fetal Neonatal Med. 2010 Oct;15(5):293-8. doi: 10.1016/j.siny.2010.02.002. Epub 2010 Mar 7.</citation>
    <PMID>20207600</PMID>
  </results_reference>
  <results_reference>
    <citation>Aly H, Elmahdy H, El-Dib M, Rowisha M, Awny M, El-Gohary T, Elbatch M, Hamisa M, El-Mashad AR. Melatonin use for neuroprotection in perinatal asphyxia: a randomized controlled pilot study. J Perinatol. 2015 Mar;35(3):186-91. doi: 10.1038/jp.2014.186. Epub 2014 Nov 13.</citation>
    <PMID>25393080</PMID>
  </results_reference>
  <results_reference>
    <citation>Fulia F, Gitto E, Cuzzocrea S, Reiter RJ, Dugo L, Gitto P, Barberi S, Cordaro S, Barberi I. Increased levels of malondialdehyde and nitrite/nitrate in the blood of asphyxiated newborns: reduction by melatonin. J Pineal Res. 2001 Nov;31(4):343-9. doi: 10.1034/j.1600-079x.2001.310409.x.</citation>
    <PMID>11703564</PMID>
  </results_reference>
  <results_reference>
    <citation>Ahmad QM, Chishti AL, Waseem N. Role of melatonin in management of hypoxic ischaemic encephalopathy in newborns: A randomized control trial. J Pak Med Assoc. 2018 Aug;68(8):1233-1237.</citation>
    <PMID>30108392</PMID>
  </results_reference>
  <results_reference>
    <citation>Roohbakhsh A, Shamsizadeh A, Hayes AW, Reiter RJ, Karimi G. Melatonin as an endogenous regulator of diseases: The role of autophagy. Pharmacol Res. 2018 Jul;133:265-276. doi: 10.1016/j.phrs.2018.01.022. Epub 2018 Feb 3.</citation>
    <PMID>29408249</PMID>
  </results_reference>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>January 14, 2019</study_first_submitted>
  <study_first_submitted_qc>January 14, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 16, 2019</study_first_posted>
  <last_update_submitted>October 10, 2019</last_update_submitted>
  <last_update_submitted_qc>October 10, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 11, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital of Ferrara</investigator_affiliation>
    <investigator_full_name>Anna Tarocco</investigator_full_name>
    <investigator_title>Medical Doctor, Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>autophagy</keyword>
  <keyword>neuroprotection</keyword>
  <keyword>melatonin</keyword>
  <keyword>Hypoxic-Ischemic Encephalopathy</keyword>
  <keyword>hypothermia</keyword>
  <keyword>newborn</keyword>
  <keyword>neurological outcome</keyword>
  <keyword>perinatal asphyxia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Diseases</mesh_term>
    <mesh_term>Brain Ischemia</mesh_term>
    <mesh_term>Hypoxia-Ischemia, Brain</mesh_term>
    <mesh_term>Ischemia</mesh_term>
    <mesh_term>Hypoxia</mesh_term>
    <mesh_term>Asphyxia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melatonin</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/NCT03806816
org study id: 23/2018/SPER/AOUFE
nct id: NCT03806816
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Protection of brain development is a major aim in the Neonatal Intensive Care Unit.
      Hypoxic-Ischemic Encephalopathy (HIE) occurs in 3-5 per 1000 births. Only 47% of neonates
      have normal outcomes. The neurodevelopmental consequences of brain injury for asphyxiated
      term infants include cerebral palsy, severe intellectual disabilities and also a number of
      minor behavioural and cognitive deficits. However, there are very few therapeutic strategies
      for the prevention or treatment of brain damage. The gold standard is hypothermic treatment
      but, according to the literature, melatonin potentially acts in synergy with hypothermia for
      neuroprotection and to improve neurologic outcomes. Melatonin appears to be a good candidate
      because of its different protective effects including reactive oxygen species scavenging,
      excitotoxic cascade blockade, modulation of neuroinflammatory pathways.

      The research study will evaluate the neuroprotective properties and the effects of Melatonin
      in association with therapeutic hypothermia for hypoxic ischemic encephalopathy.
It is a randomized double blind, placebo controlled trial on 100 neonates with moderate to
      moderately to severe hypoxic ischemic encephalopathy (HIE) . HIE infants are randomized into
      two groups: Whole body cooling group (N = 50 receive 72 hours of whole body hypothermia) and
      melatonin/ hypothermia group (N = 50; receive hypothermia and 5 daily enteral doses of
      melatonin 10 mg/kg). Serum melatonin and autophagy levels are measured at enrollment, daily
      during the hypothermic treatment, at day 5 and 7 for the two HIE groups.

      aEEG will be performed for 72 hrs during the hypothermic treatment and the re-warming. MRI
      and Spectroscopy analysis will be performed between day 5 and 7 of. After hospital discharge
      the infants will enter a follow-up program consisting in periodic clinical and developmental
      assessments until 2 years of age corrected for prematurity. An expert psychologist and a
      neonatologist will assess neurodevelopmental outcome using the Bayley Scales III at 6-12-24
      months of corrected age.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Bayley III scale
time frame: 12 months
description: Bayley scale of infant and toddler development. It measures developmental skills reached by infant and young children between 1 month and 42 months The scale is subdivided into 5 subscales Cognitive,Receptive communication,Expressive communication,Fine motor ,Gross motor.Receptive and expressive communication have a composite in language score So as fine and gross motor in motor score For all subtests raw scores correspond to scaled scores ranging from 1 to 19 with a mean of 10 and SD of 3 The composite scores are given by the sum of the corresponding subtests scaled scores.
Two parent-reported scales (Social-Emotional and Adaptive Behavior) will be collected.
measure: brain MRI
time frame: between the 5th and 7th days of life
description: to evaluate the presence of deep grey matter, PLIC, white matter, brainstem and hippocampus lesions
measure: continuous aEEG
time frame: Continuous monitoring for the first 72 hours and for the rewarmed
description: Al Naqueeb classification for aEEG will be used.Background voltage pattern will be scored in NORMAL (Lower margin >5μV,Upper margin >10μV The activity is continuous), MODERATELY ABORMAL (Lower margin <5μV, upper margin >10μV,The activity is moderately discontinuous)SEVERELY ABNORMAL/ SUPPRESSED (Lower margin <5μV, upper margin <10μV)
measure: Plasma Concentration of Melatonin
time frame: at birth, 24 hours, 48 hours, 72 hours, 5 days, 7 days of life
description: UPLC-Massa Acquity-Xevo TQD (Waters) will be used to measure melatonin concentrations in the plasma
measure: ATG5 Plasma concentration
time frame: at birth, 24 hours, 48 hours, 72 hours, 5 days, 7 days of life
description: ELISA test will be used to measure plasma levels of ATG5
arm group label: HYPOTHERMIA / MELATONIN group
arm group type: Experimental
description: HIE infants who will receive melatonin in addition to the routine cooling treatment
arm group label: HYPOTHERMIA / PLACEBO group
arm group type: Experimental
description: HIE infants who will not receive melatonin in addition to the routine cooling treatment
intervention type: Dietary Supplement
intervention name: Melatonin
description: 5 daily enteral doses of melatonin 10 mg/kg. (=2 ml/kg)
arm group label: HYPOTHERMIA / MELATONIN group
other name: Buona Circadiem
intervention type: Other
intervention name: PLACEBO group
description: 5 daily enteral doses of placebo 2 ml/kg
arm group label: HYPOTHERMIA / PLACEBO group
other name: placebo
criteria: 
gender: All
minimum age: 1 Hour
maximum age: 6 Hours
healthy volunteers: No
last name: Anna Tarocco, MD
role: Principal Investigator
affiliation: University Hospital of Ferrara
last name: Anna Tarocco, MD
phone: +390532236014
email: anna.tarocco@unife.it
last name: Paolo Pinton, Professor
phone: +390532455802
email: paolo.pinton@unife.it
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: Holy See (Vatican City State)
country: Italy
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responsible party type: Principal Investigator
investigator affiliation: University Hospital of Ferrara
investigator full name: Anna Tarocco
investigator title: Medical Doctor, Principal Investigator
mesh term: Brain Diseases
mesh term: Brain Ischemia
mesh term: Hypoxia-Ischemia, Brain
mesh term: Ischemia
mesh term: Hypoxia
mesh term: Asphyxia
mesh term: Melatonin
sharing ipd: No