- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02621944
Melatonin as a Neuroprotective Therapy in Neonates With HIE Undergoing Hypothermia
Study Overview
Status
Conditions
Detailed Description
Thirty subjects will be enrolled in a dose escalation study. Subjects 1-10 will receive melatonin (0.5 mg/kg). If that dose proves to be safe, subjects 11-20 will receive an increased dose of melatonin (3 mg/kg). Subjects 21-30 will receive a dose increased to the targeted projected therapeutic dose (5 mg/kg).
The 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.
Study Type
Enrollment (Anticipated)
Phase
- Early Phase 1
Contacts and Locations
Study Contact
- Name: Livia Sura, MPH, CPH
- Phone Number: 3522738706
- Email: livia.sura@peds.ufl.edu
Study Contact Backup
- Name: Kristine Boykin, BSN
- Phone Number: 3522738706
- Email: kristineboykin@ufl.edu
Study Locations
-
-
Florida
-
Gainesville, Florida, United States, 32610
- Recruiting
- University of Florida
-
Contact:
- Kristine L Boykin, BSN
- Phone Number: 352-273-8985
- Email: kristineboykin@ufl.edu
-
Contact:
- Michael Weiss, MD
- Phone Number: 3522738985
- Email: weissmd@peds.ufl.edu
-
Principal Investigator:
- Michael D Weiss, MD
-
Principal Investigator:
- Giuseppe Buonocore, MD
-
Sub-Investigator:
- Candace Rossignol, Sr. Lab Tech
-
Sub-Investigator:
- Ronald Hayes, MD
-
Sub-Investigator:
- Kristine Boykin, BSN
-
Principal Investigator:
- Rajan Wadhawan, MD
-
Sub-Investigator:
- Nicole Copenhaver, BA, ASN
-
Sub-Investigator:
- Ganna Zalevska, BS, RRT
-
Orlando, Florida, United States, 32803
- Recruiting
- Florida Hospital for Children
-
Principal Investigator:
- Rajan Wadhawan, MD
-
Contact:
- Rajan Wadhawan, M.D.
- Phone Number: 407-303-2528
- Email: Rajan.Wadhawan.MD@flhosp.org
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Eligible infants are >36 0/7th weeks gestation,
- pH (cord or neonatal) <7.0,
- base deficit >16 mEq/L,
- no available blood gas,
- a cord blood/first hour of life blood gas with pH > 7.0 and < 7.15,
- base deficit between 10 and 15.9 mEq/L,
- infants must have a history of an acute perinatal event,
- either a 10-minute Apgar < 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.
Exclusion Criteria:
- 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/or chromosomal abnormalities.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Participants 1-10
This group will receive a 0.5 mg/kg enteral dose of Melatonin. The first dose will be administered via enteral route within 12 hours of life with a target of 6 hours of life. The melatonin will be administered as a single dose for the first 5 participants in allowing the investigators to determine if the dosing frequency has the potential to decrease in the elimination with hypothermia. The next 5 subjects who will receive multiple doses if there are not any safety concerns. Additionally, the participants will have the following test performed: Magnetic Resonance Imaging (MRI), Neurological Outcome Assessment, Pharmacokinetics, and safety monitoring. |
Participants 1-10 will receive a 0.5 mg/kg enteral dose of Melatonin.
Participants 11-20 will receive Melatonin dose of 3 mg/kg enteral.
Participants 21-30 will receive Melatonin dose of 5 mg/kg enterally.
All participants will receive an MRI between 7-12 days of age.
Other Names:
All participants will receive pharmacokinetics to test the amount of melatonin in the blood.
All participants will receive the Bayley-III Scores and Subsets for neurological outcome assessments.
|
Experimental: Participants 11-20
This group will the Melatonin dose of 3 mg/kg enteral, only if the group Participants 1-10 has meet the safety goals. The first dose will be administered via enteral route within 12 hours of life with a target of 6 hours of life. The melatonin will be administered as a single dose for the first 5 participants in allowing the investigators to determine if the dosing frequency has the potential to decrease in the elimination with hypothermia. The next 5 subjects who will receive multiple doses if there are not any safety concerns. Additionally, the participants will have the following test performed: Magnetic Resonance Imaging (MRI), Neurological Outcome Assessment, Pharmacokinetics, and safety monitoring. |
Participants 1-10 will receive a 0.5 mg/kg enteral dose of Melatonin.
Participants 11-20 will receive Melatonin dose of 3 mg/kg enteral.
Participants 21-30 will receive Melatonin dose of 5 mg/kg enterally.
All participants will receive an MRI between 7-12 days of age.
Other Names:
All participants will receive pharmacokinetics to test the amount of melatonin in the blood.
All participants will receive the Bayley-III Scores and Subsets for neurological outcome assessments.
|
Experimental: Participants 21-30
This group will receive Melatonin dose of 5 mg/kg enterally, only if the group Participants 11-20 has meet the safety goals. The first dose will be administered via enteral route within 12 hours of life with a target of 6 hours of life. The melatonin will be administered as a single dose for the first 5 participants in allowing the investigators to determine if the dosing frequency has the potential to decrease in the elimination with hypothermia. The next 5 subjects who will receive multiple doses if there are not any safety concerns. Additionally, the participants will have the following test performed: Magnetic Resonance Imaging (MRI), Neurological Outcome Assessment, Pharmacokinetics, and safety monitoring. |
Participants 1-10 will receive a 0.5 mg/kg enteral dose of Melatonin.
Participants 11-20 will receive Melatonin dose of 3 mg/kg enteral.
Participants 21-30 will receive Melatonin dose of 5 mg/kg enterally.
All participants will receive an MRI between 7-12 days of age.
Other Names:
All participants will receive pharmacokinetics to test the amount of melatonin in the blood.
All participants will receive the Bayley-III Scores and Subsets for neurological outcome assessments.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To identify the maximum tolerated dose of Melatonin
Time Frame: Changes in Baseline to day 3
|
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
|
Bayley-III Index Scores (Cognitive, Language, and Motor) will be used for neurological outcome assessment
Time Frame: Approximately 18 - 20 Months
|
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 < 85) will be classified as "poor outcome" while higher scores will be classified as "good outcome".
|
Approximately 18 - 20 Months
|
Peak Plasma Concentration (Cmax) of Melatonin 0.5 mg/kg.
Time Frame: 0 (baseline), 3, 5, 6, 12, 24, 48, 96 hours and day 14 (one sample)
|
HPLC-ESI/MS/MS 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)
|
Number of participants with treatment-related adverse events as assessed by MedDRA ??? This is something the PI/Team needs to agree on which one to use.
Time Frame: Baseline ongoing to Day 14
|
Incidence/Grade 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
|
Peak Plasma Concentration (Cmax) of Melatonin 3 mg/kg.
Time Frame: 0 (baseline), 3, 5, 6, 12, 24, 48, 96 hours and day 14 (one sample)
|
HPLC-ESI/MS/MS 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.
|
0 (baseline), 3, 5, 6, 12, 24, 48, 96 hours and day 14 (one sample)
|
Peak Plasma Concentration (Cmax) of Melatonin 5 mg/kg.
Time Frame: 0 (baseline), 3, 5, 6, 12, 24, 48, 96 hours and day 14 (one sample)
|
HPLC-ESI/MS/MS 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)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Bayley-III Index Scores Subscales (Receptive and Expressive Language, Fine and Gross Motor) will be used for neurological outcome assessment
Time Frame: Approximately 18 - 20 Months
|
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 < 85) will be classified as "poor outcome" while higher scores will be classified as "good outcome".
|
Approximately 18 - 20 Months
|
Evaluation of The Impact of Melatonin using Magnetic Resonance Image (MRI)
Time Frame: Approximately 7 - 12 days
|
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
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Michael D Weiss, MD, University of Florida
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Cerebrovascular Disorders
- Central Nervous System Diseases
- Nervous System Diseases
- Signs and Symptoms, Respiratory
- Body Temperature Changes
- Hypoxia
- Hypoxia, Brain
- Brain Ischemia
- Brain Diseases
- Hypothermia
- Hypoxia-Ischemia, Brain
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Protective Agents
- Antioxidants
- Melatonin
Other Study ID Numbers
- IRB201500886
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Hypoxic Ischemic Encephalopathy
-
Johns Hopkins UniversityUniversity of MarylandCompletedEncephalopathy, Hypoxic-IschemicUnited States
-
Sajjad RahmanUnknownSevere Hypoxic Ischemic Encephalopathy | Moderate Hypoxic Ischemic EncephalopathyTurkey, Egypt, Malaysia, Qatar, Saudi Arabia, United Arab Emirates
-
NICHD Neonatal Research NetworkEunice Kennedy Shriver National Institute of Child Health and Human Development... and other collaboratorsCompletedHypoxia, Brain | Hypoxia-Ischemia, Brain | Hypoxic-Ischemic Encephalopathy | Infant, Newborn | Ischemic-Hypoxic Encephalopathy | Encephalopathy, Hypoxic-IschemicUnited States
-
Fondazione Policlinico Universitario Agostino Gemelli...RecruitingEncephalopathy, Hypoxic IschemicItaly
-
Cliniques universitaires Saint-Luc- Université...Active, not recruitingEncephalopathy, Hypoxic-IschemicBelgium
-
University Hospital, GrenobleUnknownIschemic-Hypoxic EncephalopathyFrance
-
NICHD Neonatal Research NetworkEunice Kennedy Shriver National Institute of Child Health and Human Development... and other collaboratorsTerminatedHypoxia, Brain | Hypoxia-Ischemia, Brain | Hypoxic-Ischemic Encephalopathy | Infant, Newborn | Ischemic-Hypoxic Encephalopathy | Encephalopathy, Hypoxic-IschemicUnited States
-
Navy General Hospital, BeijingDaping Hospital and the Research Institute of Surgery of the Third Military... and other collaboratorsUnknownHypoxic-Ischemic EncephalopathyChina
-
Istanbul Training and Research HospitalCompletedHypoxic-Ischemic EncephalopathyTurkey
-
University of FloridaAmerican Heart AssociationCompleted
Clinical Trials on Melatonin
-
Duquesne UniversityCompleted
-
Peking Union Medical College HospitalCompleted
-
UnivatesAline Patrícia Brietzke; Ana Paula CostellaRecruitingPerimenopausal DisorderBrazil
-
Chinese PLA General HospitalUnknown
-
Assaf-Harofeh Medical CenterNeurim Pharmaceuticals Ltd.UnknownMild Cognitive Impairment (MCI)Israel
-
Qazvin University Of Medical SciencesCompletedPost Partum Haemorrhage in Patients Undergoing Cesarean SectionIran, Islamic Republic of
-
Mayo ClinicRecruitingParkinson Disease | Rapid Eye Movement Sleep Behavior DisorderUnited States
-
Pharmavite LLCKGK Science Inc.Completed
-
Ain Shams UniversityCompletedCerebral Palsy | Growth | Children, Only | MelatoninEgypt
-
Technological Centre of Nutrition and Health, SpainUniversity Rovira i Virgili; Hospital Universitari Sant Joan de Reus; Fundació... and other collaboratorsCompleted