Newborn Hypoxic Ischemic EncephalopathyPhase 1NCT01904786
Melatonin Treatment for Newborn Infants With Moderate to Severe Hypoxic Ischemic Encephalopathy
A Phase 1 study testing Melatonin in people with Newborn Hypoxic Ischemic Encephalopathy, run by St. Louis University at 1 site in United States.
Trial summary
During the birth process certain conditions can cause oxygen delivery and/or blood flow to the baby's brain to become interrupted. This can cause permanent brain damage. Brain damage occurs in two phases. The first occurs at the time of injury when brain cells in the affected area 'die'. Read more about this study
- Who is it for?
- Ages 1 hour to 8 hours
- Conditions the study is for
- Newborn Hypoxic Ischemic Encephalopathy
- What is being tested?
- Melatonin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2014to Nov 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 hour to 8 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Infants with moderate to severe hypoxic ischemic encephalopathy ≥36 weeks
- First dose of study drug given within 8 hours of birth
Who cannot join
- Major chromosomal or congenital defects
Trial locations and contacts
1 site in 1 country.
United States1 site
Cardinal Glennnon Children's Medical Center
St Louis, Missouri, 63104
About this study
During the birth process certain conditions can cause oxygen delivery and/or blood flow to the baby's brain to become interrupted. This can cause permanent brain damage. Brain damage occurs in two phases. The first occurs at the time of injury when brain cells in the affected area 'die'. There is nothing that can be done about this. The second phase of injury occurs over the next few days. This second phase is caused by inflammation and release of toxic chemicals from the injured site. Cooling the baby to a temperature of 92.5° F, for 3 days has been shown to reduce the second phase of injury and bran death. All babies will receive the benefit of cooling. Although cooling helps it does not completely stop the second phase of injury.
Melatonin is a naturally occurring hormone that is produced by the brain, and helps regulate the sleep-wake cycle. It has the potential to stop the second phase of brain injury by inhibiting inflammation and release of toxic chemicals. The reason for this research is to find out if melatonin can or cannot improve the outcome of babies with this kind of brain damage. Every baby enrolled in the study has a 50:50 chance of getting melatonin. A total of six doses of medicine will be given. The baby's brain function will be assessed by an EEG, brain oxygen monitoring, and a neurologic examination at 18 months of life. All of these are routinely used as part of standard care for patients with this kind of problem. The only difference is that half the babies enrolled in the study will get the drug called melatonin and the other half will receive placebo. The dose of melatonin being used in the study is higher than the amount normally produced by the body. No side-effects of this dose have been reported in other research studies using melatonin in newborn and premature babies.
Read the detailed description
This is a double-blind randomized study. All babies less than eight hours old, admitted to the NICU at Cardinal Glennon Children's Medical Center, with moderate to severe HIE that qualify for whole body cooling will be eligible for enrollment in the study. Whole body cooling is part of standard treatment for babies with moderate to severe HIE, and the criteria for diagnosis and cooling are well established. After consent is obtained babies will be randomly assigned to melatonin treatment or control groups (standard treatment) using a 4-block randomization design, by opening a sealed opaque sequentially numbered envelope by the study pharmacist. A log of assignments will be maintained by the study pharmacist. The clinical team will be blinded as to the assignment. Patients assigned to melatonin treatment will receive 40 mg melatonin (PureBulk, CA, USA) in 5 mL of vehicle (1:90 mix ethanol/saline) every 8 hours for a total of six doses. Patients assigned to the control group will receive 5 mL of vehicle only every 8 hours for a total of six doses. All doses will be administered via a nasogastric tube by the nurse assigned to the patient. Placement of a nasogastric tube is part of standard care for babies with HIE. Administration of the first dose within eight hours of life is mandatory for the study.
EEG analysis is part of standard neurologic evaluation for patients with HIE, and is done once the patient has been rewarmed to normal body temperature (by 78-80 hours after starting whole body cooling). A 24 hour multichannel video-EEG (Nihon Kohden 9100A, Nihon Kohden USA Inc.) using the 10-20 system of electrode placement modified for neonates will be performed between 80 and 100 hours after initiation of the cooling protocol. The duration of each seizure will be added together for the entirety of the recording to obtain the seizure burden (total seizure time).
Anticonvulsant treatment will assessed at the time of discharge whether the patient is on any, one, or more anticonvulsants.
Cerebral tissue oxygenation (rSO2) will be monitored non-invasively by applying the NIRS probe to the forehead and attaching it to the INVOS monitor (Somanetics, MI, USA). The probe is very similar to the oxygen saturation oximeter probe that is routinely used in newborns. Cerebral tissue oxygenation will be continuously monitored until re-warming is complete. Data will be collected at the start of monitoring and then every six hours.
A brain MRI is not required for the study, but if it is obtained then the results may be included in the data collected.
- Conditions
- Newborn Hypoxic Ischemic Encephalopathy
- Being tested
- Melatonin, placebo
- Keywords
- Hypoxic Ischemic Encephalopathy, Newborn, Outcomes, Melatonin
- Medical subject headings
- Hypoxia-Ischemia, Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MelatoninDrug
placeboDrug
| Study group | Role | What they receive |
|---|---|---|
| Melatonin | Experimental | Melatonin 40 mg every 8 hours for a total of six doses given over 48 hours orally (per nasogastric tube). Receives: Drug: Melatonin |
| Placebo | Placebo comparator | Placebo consists of the solvent solution without melatonin. Solvent solution consists of 5 mL of saline/alcohol mixture in a ratio of 90:1 Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neurodevelopment at 18 months of life (BSID-III)
The Bayley Scales of Infant Development III exam will be administered at 18 months of life to assess neurodevelopment.
Measured: 18 months
Secondary outcomes (3)
Seizure burden
Measured: Assessed on day 3-4 of life
Reduction in Burst Suppression
Measured: Assessed on day 3-4 of life
Improved cerebral oxygenation
Measured: First 3-4 days of life
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2013 (estimated)
- Study startApr 2014
- Primary completionDec 2017 (estimated)
- Study completionNov 2018 (estimated)
Why it stopped: Lack of enrollment of suitable candidates
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Newborn Hypoxic Ischemic EncephalopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Louis University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Farouk Sadiq, MD, Principal investigator, St. Louis University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01904786
- Sponsor's protocol ID
- SLU22484
- Status last verified
- Jan 2015
- First submitted
- 17 Jul 2013
- Last updated
- 3 Jul 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Melatonin Treatment for Newborn Infants With Moderate to Severe Hypoxic Ischemic Encephalopathy
- ClinicalTrials.gov ID
- NCT01904786
- Acronym / sponsor ID
- SLU22484
- Conditions
- Newborn Hypoxic Ischemic Encephalopathy
- Keywords
- Hypoxic Ischemic Encephalopathy, Newborn, Outcomes, Melatonin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of enrollment of suitable candidates
- Enrolment
- 0 participants (actual)
- Lead sponsor
- St. Louis UniversityUniversity, hospital or other
- Study start
- Apr 2014
- Primary completion
- Dec 2017 (estimated)
- Study completion
- Nov 2018 (estimated)
- First posted
- 22 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
During the birth process certain conditions can cause oxygen delivery and/or blood flow to the baby's brain to become interrupted. This can cause permanent brain damage. Brain damage occurs in two phases. The first occurs at the time of injury when brain cells in the affected area 'die'. There is nothing that can be done about this. The second phase of injury occurs over the next few days. This second phase is caused by inflammation and release of toxic chemicals from the injured site. Cooling the baby to a temperature of 92.5° F, for 3 days has been shown to reduce the second phase of injury and bran death. All babies will receive the benefit of cooling. Although cooling helps it does not completely stop the second phase of injury.
Melatonin is a naturally occurring hormone that is produced by the brain, and helps regulate the sleep-wake cycle. It has the potential to stop the second phase of brain injury by inhibiting inflammation and release of toxic chemicals. The reason for this research is to find out if melatonin can or cannot improve the outcome of babies with this kind of brain damage. Every baby enrolled in the study has a 50:50 chance of getting melatonin. A total of six doses of medicine will be given. The baby's brain function will be assessed by an EEG, brain oxygen monitoring, and a neurologic examination at 18 months of life. All of these are routinely used as part of standard care for patients with this kind of problem. The only difference is that half the babies enrolled in the study will get the drug called melatonin and the other half will receive placebo. The dose of melatonin being used in the study is higher than the amount normally produced by the body. No side-effects of this dose have been reported in other research studies using melatonin in newborn and premature babies.
Detailed description
This is a double-blind randomized study. All babies less than eight hours old, admitted to the NICU at Cardinal Glennon Children's Medical Center, with moderate to severe HIE that qualify for whole body cooling will be eligible for enrollment in the study. Whole body cooling is part of standard treatment for babies with moderate to severe HIE, and the criteria for diagnosis and cooling are well established. After consent is obtained babies will be randomly assigned to melatonin treatment or control groups (standard treatment) using a 4-block randomization design, by opening a sealed opaque sequentially numbered envelope by the study pharmacist. A log of assignments will be maintained by the study pharmacist. The clinical team will be blinded as to the assignment. Patients assigned to melatonin treatment will receive 40 mg melatonin (PureBulk, CA, USA) in 5 mL of vehicle (1:90 mix ethanol/saline) every 8 hours for a total of six doses. Patients assigned to the control group will receive 5 mL of vehicle only every 8 hours for a total of six doses. All doses will be administered via a nasogastric tube by the nurse assigned to the patient. Placement of a nasogastric tube is part of standard care for babies with HIE. Administration of the first dose within eight hours of life is mandatory for the study.
EEG analysis is part of standard neurologic evaluation for patients with HIE, and is done once the patient has been rewarmed to normal body temperature (by 78-80 hours after starting whole body cooling). A 24 hour multichannel video-EEG (Nihon Kohden 9100A, Nihon Kohden USA Inc.) using the 10-20 system of electrode placement modified for neonates will be performed between 80 and 100 hours after initiation of the cooling protocol. The duration of each seizure will be added together for the entirety of the recording to obtain the seizure burden (total seizure time).
Anticonvulsant treatment will assessed at the time of discharge whether the patient is on any, one, or more anticonvulsants.
Cerebral tissue oxygenation (rSO2) will be monitored non-invasively by applying the NIRS probe to the forehead and attaching it to the INVOS monitor (Somanetics, MI, USA). The probe is very similar to the oxygen saturation oximeter probe that is routinely used in newborns. Cerebral tissue oxygenation will be continuously monitored until re-warming is complete. Data will be collected at the start of monitoring and then every six hours.
A brain MRI is not required for the study, but if it is obtained then the results may be included in the data collected.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Melatonin | Experimental | Drug: MelatoninMelatonin 40 mg every 8 hours for a total of six doses given over 48 hours orally (per nasogastric tube). |
| Placebo | Placebo comparator | Drug: placeboPlacebo consists of the solvent solution without melatonin. Solvent solution consists of 5 mL of saline/alcohol mixture in a ratio of 90:1 |
Who may qualify
- Ages
- 1 hour to 8 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Infants with moderate to severe hypoxic ischemic encephalopathy ≥36 weeks
- First dose of study drug given within 8 hours of birth
Key exclusion criteria (1 listed)
- Major chromosomal or congenital defects
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Melatonin | Drug | Melatonin |
| placebo | Drug | Placebo |
Primary outcome
Neurodevelopment at 18 months of life (BSID-III)
Time frame: 18 months
The Bayley Scales of Infant Development III exam will be administered at 18 months of life to assess neurodevelopment.
3 secondary outcomes
Seizure burden
Time frame: Assessed on day 3-4 of life
Reduction in Burst Suppression
Time frame: Assessed on day 3-4 of life
Improved cerebral oxygenation
Time frame: First 3-4 days of life
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2015.
Related trials for Newborn Hypoxic Ischemic Encephalopathy
RecruitingPhase 2
The PROTECT-HIE Pilot Trial
Hypoxic-ischemic Encephalopathy (HIE)
RecruitingPhase 2/3
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of RLS-0071 in Newborns With Moderate or Severe Hypoxic-Ischemic Encephalopathy Undergoing Therapeutic Hypothermia
Hypoxic-Ischemic Encephalopathy
Not yet recruiting
Levetiracetam as an Adjuvant Therapy to Hypothermia in Neonatal Asphyxia
Hypoxic Ischemic Encephalopathy of Newborn, Neuro-protection
RecruitingPhase 2
A Dose Escalation Study of Levetiracetam in the Treatment of Neonatal Seizures
Neonatal Seizure, Neonatal Encephalopathy
RecruitingObservational study
Continuous Monitoring of Body Temperature in Neonates During Therapeutic Hypothermia
Therapeutic Hypothermia, Neonatal Hypoxic-Ischemic Encephalopathy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Farouk Sadiq, MD principal investigator
St. Louis University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Melatonin in people with Newborn Hypoxic Ischemic Encephalopathy, run by St. Louis University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 3 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neurodevelopment at 18 months of life (BSID-III) (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2015.