[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT02621944":3,"trial-entities:NCT02621944":164,"trial-summary:NCT02621944":167},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":6,"overall_status":7,"completion_date":8,"status_verified_date":9,"last_update_date":10,"start_date":11,"sponsor_name":12,"lead_sponsor_class":13,"has_dmc":14,"brief_summary":15,"detailed_description":16,"conditions":17,"keywords":19,"study_type":20,"primary_purpose":21,"phases":22,"enrollment_info":24,"interventions":27,"primary_outcomes":51,"secondary_outcomes":73,"sex":81,"minimum_age":82,"maximum_age":83,"healthy_volunteers":84,"eligibility_criteria":85,"std_ages":102,"locations":104,"central_contacts":154,"overall_officials":160,"references":162,"see_also_links":163},"NCT02621944","IRB201500886","Melatonin as a Neuroprotective Therapy in Neonates With HIE Undergoing Hypothermia","RECRUITING","2027-03","2026-06","2026-06-29","2016-11-09","University of Florida","OTHER",true,"Hypoxic-Ischemic Encephalopathy (HIE) occurs in 20 per 1000 births. Only 47% of neonates treated with the state of the art therapy (induced systemic hypothermia) have normal outcomes. Therefore, other promising therapies that potentially work in synergy with hypothermia to improve neurologic outcomes need to be tested. One potential agent is melatonin. Melatonin is a naturally occurring substance produced mainly from the pineal gland. Melatonin is widely known for its role in regulating the circadian rhythm, but it has many other effects that may benefit infants with HI injury. Melatonin serves as a free radical scavenger, decreases inflammatory cytokines, and stimulates anti-oxidant enzymes. Therefore, melatonin may interrupt several key components in the pathophysiology of HIE, in turn minimizing cell death and improving outcomes. The research study will evaluate the neuroprotective properties and appropriate dose of Melatonin to give to infants undergoing therapeutic hypothermia for hypoxic ischemic encephalopathy.","Thirty subjects will be enrolled in a dose escalation study. Subjects 1-10 will receive melatonin (0.5 mg\u002Fkg). If that dose proves to be safe, subjects 11-20 will receive an increased dose of melatonin (3 mg\u002Fkg). Subjects 21-30 will receive a dose increased to the targeted projected therapeutic dose (5 mg\u002Fkg).\n\nThe serum concentration of melatonin and capture adverse event reports during this dose escalation study in neonates undergoing hypothermia and the long-term safety and potential efficacy via developmental follow-up performed at 18-22 months of age. In addition, this study will determine the effect of melatonin on the inflammatory cascade, oxidative stress, free radical production, and serum biomarkers of brain injury in neonates undergoing hypothermia.",[18],"Hypoxic Ischemic Encephalopathy",[],"INTERVENTIONAL","TREATMENT",[23],"EARLY_PHASE1",{"count":25,"type":26},70,"ESTIMATED",[28,36,42,46],{"type":29,"name":30,"description":31,"armGroupLabels":32},"DRUG","Melatonin","Participants 1-10 will receive a 0.5 mg\u002Fkg enteral dose of Melatonin. Participants 11-20 will receive Melatonin dose of 3 mg\u002Fkg enteral. Participants 21-30 will receive Melatonin dose of 5 mg\u002Fkg enterally.",[33,34,35],"Participants 1-10","Participants 11-20","Participants 21-30",{"type":13,"name":37,"description":38,"armGroupLabels":39,"otherNames":40},"Magnetic Resonance Imaging","All participants will receive an MRI between 7-12 days of age.",[33,34,35],[41],"MRI",{"type":13,"name":43,"description":44,"armGroupLabels":45},"Pharmacokinetics","All participants will receive pharmacokinetics to test the amount of melatonin in the blood.",[33,34,35],{"type":47,"name":48,"description":49,"armGroupLabels":50},"BEHAVIORAL","Neurological Outcome Assessment","All participants will receive the Bayley-III Scores and Subsets for neurological outcome assessments.",[33,34,35],[52,56,60,64,68,71],{"measure":53,"description":54,"timeFrame":55},"To identify the maximum tolerated dose of Melatonin","The maximum tolerated dose (MTD) is defined as the highest dose level without adverse events in no more than 1 out of 6 patients","Changes in Baseline to day 3",{"measure":57,"description":58,"timeFrame":59},"Bayley-III Index Scores (Cognitive, Language, and Motor) will be used for neurological outcome assessment","All raw scores will be transformed into norm-referenced standard scores (scale mean = 100 with s.d. = 15) using the Bayley-III scoring software published with the test. To dichotomize \"good\" and \"poor\" outcomes for statistical analysis, standardized scores that are at or greater than one standard deviation below the normative sample mean published with the test (i.e., standard scores \\\u003C 85) will be classified as \"poor outcome\" while higher scores will be classified as \"good outcome\".","Approximately 18 - 20 Months",{"measure":61,"description":62,"timeFrame":63},"Peak Plasma Concentration (Cmax) of Melatonin 0.5 mg\u002Fkg.","HPLC-ESI\u002FMS\u002FMS will be used to measure melatonin concentrations in the serum samples. The two-way ANOVA (treatments are dose level and timepoint) framework for testing. Testing will be done using a likelihood ratio test, either using large-sample theory approximation or using bootstrap.","0 (baseline), 3, 5, 6, 12, 24, 48, 96 hours and day 14 (one sample)",{"measure":65,"description":66,"timeFrame":67},"Number of participants with treatment-related adverse events as assessed by MedDRA ??? This is something the PI\u002FTeam needs to agree on which one to use.","Incidence\u002FGrade of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), laboratory abnormalities Percentage and number of subjects who discontinued for adverse event","Baseline ongoing to Day 14",{"measure":69,"description":70,"timeFrame":63},"Peak Plasma Concentration (Cmax) of Melatonin 3 mg\u002Fkg.","HPLC-ESI\u002FMS\u002FMS will be used to measure melatonin concentrations in the serum. The two-way ANOVA (treatments are dose level and timepoint) framework for testing. Testing will be done using a likelihood ratio test, either using large-sample theory approximation or using bootstrap.",{"measure":72,"description":62,"timeFrame":63},"Peak Plasma Concentration (Cmax) of Melatonin 5 mg\u002Fkg.",[74,77],{"measure":75,"description":76,"timeFrame":59},"Bayley-III Index Scores Subscales (Receptive and Expressive Language, Fine and Gross Motor) will be used for neurological outcome assessment","The four performance-based subscales of the Bayley-III Index Scores (Receptive and Expressive Language, Fine and Gross Motor) and two parent-reported scales (Social-Emotional and Adaptive Behavior) will be collected. All raw scores will be transformed into norm-referenced standard scores (scale mean = 100 with s.d. = 15) using the Bayley-III scoring software published with the test. To dichotomize \"good\" and \"poor\" outcomes for statistical analysis, standardized scores that are at or greater than one standard deviation below the normative sample mean published with the test (i.e., standard scores \\\u003C 85) will be classified as \"poor outcome\" while higher scores will be classified as \"good outcome\".",{"measure":78,"description":79,"timeFrame":80},"Evaluation of The Impact of Melatonin using Magnetic Resonance Image (MRI)","The MRI study scores of neonates treated with hypothermia plus melatonin will be compared with historical controls that have matched Sarnat exams (exam of HIE severity at the time of admission).","Approximately 7 - 12 days","ALL",null,"6 Hours",false,{"inclusion":86,"exclusion":97,"raw_text":101},[87,88,89,90,91,92,93,94,95,96],"Eligible infants are \\>36 0\u002F7th weeks gestation,","pH (cord or neonatal) \\\u003C7.0,","base deficit \\>16 mEq\u002FL,","no available blood gas,","a cord blood\u002Ffirst hour of life blood gas with pH \\> 7.0 and \\\u003C 7.15,","base deficit between 10 and 15.9 mEq\u002FL,","infants must have a history of an acute perinatal event,","either a 10-minute Apgar \\\u003C 5 or a continued need for ventilation,","All infants must have signs of encephalopathy within 6 hours of age using the modified Sarnat scoring system,","neonates cooled within 6 hours of birth will be included in the study.",[98,99,100],"suspected inborn errors of metabolism (elevated ammonia) and hypoglycemia,","clinical signs and symptoms consistent with meningitis detected upon sepsis evaluation,","a diagnosis of congenital abdominal surgical problems along with multiple congenital anomalies and\u002For chromosomal abnormalities.","Inclusion Criteria:\n\n* Eligible infants are \\>36 0\u002F7th weeks gestation,\n* pH (cord or neonatal) \\\u003C7.0,\n* base deficit \\>16 mEq\u002FL,\n* no available blood gas,\n* a cord blood\u002Ffirst hour of life blood gas with pH \\> 7.0 and \\\u003C 7.15,\n* base deficit between 10 and 15.9 mEq\u002FL,\n* infants must have a history of an acute perinatal event,\n* either a 10-minute Apgar \\\u003C 5 or a continued need for ventilation,\n* All infants must have signs of encephalopathy within 6 hours of age using the modified Sarnat scoring system,\n* neonates cooled within 6 hours of birth will be included in the study.\n\nExclusion Criteria:\n\n* suspected inborn errors of metabolism (elevated ammonia) and hypoglycemia,\n* clinical signs and symptoms consistent with meningitis detected upon sepsis evaluation,\n* a diagnosis of congenital abdominal surgical problems along with multiple congenital anomalies and\u002For chromosomal abnormalities.",[103],"CHILD",[105,141],{"facility":12,"status":7,"city":106,"state":107,"zip":108,"country":109,"contacts":110,"geoPoint":138},"Gainesville","Florida","32610","United States",[111,116,120,123,125,128,130,132,134,136],{"name":112,"role":113,"phone":114,"email":115},"Alison A McMurray, M.A.M.C.","CONTACT","352-627-5016","amcmurra@ufl.edu",{"name":117,"role":113,"phone":118,"email":119},"Michael Weiss, MD","3522738985","weissmd@peds.ufl.edu",{"name":121,"role":122},"Michael D Weiss, MD","PRINCIPAL_INVESTIGATOR",{"name":124,"role":122},"Giuseppe Buonocore, MD",{"name":126,"role":127},"Candace Rossignol, Sr. Lab Tech","SUB_INVESTIGATOR",{"name":129,"role":127},"Ronald Hayes, MD",{"name":131,"role":127},"Kristine Boykin, BSN",{"name":133,"role":122},"Rajan Wadhawan, MD",{"name":135,"role":127},"Nicole Copenhaver, BA, ASN",{"name":137,"role":127},"Ganna Zalevska, BS, RRT",{"lat":139,"lon":140},29.65163,-82.32483,{"facility":142,"status":7,"city":143,"state":107,"zip":144,"country":109,"contacts":145,"geoPoint":151},"Florida Hospital for Children","Orlando","32803",[146,150],{"name":147,"role":113,"phone":148,"email":149},"Rajan Wadhawan, M.D.","407-303-2528","Rajan.Wadhawan.MD@flhosp.org",{"name":133,"role":122},{"lat":152,"lon":153},28.53834,-81.37924,[155,157],{"name":112,"role":113,"phone":156,"email":115},"3526275016",{"name":131,"role":113,"phone":158,"email":159},"3522738706","kristineboykin@ufl.edu",[161],{"name":121,"affiliation":12,"role":122},[],[],{"nct_id":4,"conditions":165,"biomarkers":166},[18],[],{"nct_id":4,"found":14,"summary":168,"prompt_version":178},{"design":169,"status":170,"heading":171,"summary":172,"follow_up":173,"word_count":174,"commitments":175,"compensation":176,"drugs_mentioned":177},"This is an interventional study with 30 participants, divided into three groups to test increasing doses of melatonin. The study aims to identify the maximum tolerated dose.","completed","Melatonin for Neonates with Hypoxic Ischemic Encephalopathy (HIE)","This study is looking at whether melatonin can help babies with Hypoxic Ischemic Encephalopathy (HIE), a brain injury that can happen around birth. Currently, only about half of babies treated with cooling therapy (hypothermia) have good outcomes. Researchers want to see if melatonin, a natural substance, can work with hypothermia to improve these outcomes. This study will test different doses of melatonin (0.5 mg\u002Fkg, 3 mg\u002Fkg, and 5 mg\u002Fkg) to find the safest and most effective amount. We are looking for babies who are 36 weeks gestation or older, within 6 hours of birth, and meet specific blood test criteria related to HIE. The goal is to see how well melatonin is tolerated and if it can improve brain development, measured around 18-20 months of age.","Participants will have neurological outcome assessments performed at approximately 18-20 months of age.",126,"Participants will receive melatonin doses, have blood tests to measure melatonin levels, and undergo an MRI scan between 7-12 days of age. Neurological assessments will be performed around 18-20 months of age.","Not stated in the trial record.",[30],"v2"]