MalondialdehydeNCT04235673
Oral Melatonin as Neuroprotectant in Preterm Infants
A study testing melatonin in people with Malondialdehyde and Melatonin, run by Francesca Garofoli at 4 sites in Italy.
Trial summary
Preterm newborns survival rates are improved, but long-term disabilities are still common. Major destructive focal lesions became less common, the most predominant lesion at present is diffuse white matter (WM damage). Read more about this study
- Who is it for?
- Ages 25 to 30 weeks
- Conditions the study is for
- Malondialdehyde, Melatonin
- 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
- 60 participants
- Where
- 4 sitesItaly
- Study dates
- 25 May 2020to 11 Oct 2022
- Phase
- Interventional
- 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 25 to 30 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- preterm newborns gestational age GA < 29+6 weeks + day
- able to receive min 20ml/kg/day enteral nutrition, within 96 hours from birth
- written informed consent by both the parents.
Who cannot join
- preterm newborns GA > 29+6 weeks + days
- not able to receive enteral nutrition (min 20 ml/kg/die) within 96 hours of life
- infants with genetic and/or congenital metabolic or chronic diseases
- intraventricular hemorrhage (IVH) ≥ III,
- parents refusing to sign a written informed consent
Trial locations and contacts
4 sites in 1 country.
Italy4 sites
Child and Adolescence Neuropsychiatry Unit, Children's Hospital "Spedali Civili" of Brescia, 25123 Brescia, Italy.
Brescia, BS, 25123
Neonatal Intensive Care Unit, Children's Hospital, University Hospital "Spedali Civili" Brescia, 25123 Brescia, Italy.
Brescia, BS, 25123
Fondazione IRCCS Mondino
Pavia, PV, 27100
Neonatal Unit and NICU, Radiology, Clinical Chemistry Lab., Fondazione IRCCS Policlinico S. Matteo.
Pavia, PV, 27100
About this study
Official title: Oral Melatonin as Neuroprotectant in Preterm Infants .A Prospective, Double Blind vs Placebo, Parallel Arms Study
Preterm newborns survival rates are improved, but long-term disabilities are still common. Major destructive focal lesions became less common, the most predominant lesion at present is diffuse white matter (WM damage). Melatonin (ME) serves as a neuroprotectant cerebral ischemia through its potent anti-oxidant/-inflammatory effect. Preclinical studies demonstrated that protects the developing brain by preventing abnormal myelination and inflammatory glial reaction. Clinical studies demonstrated ME ability in reducing brain damage after neonatal Hypoxic Ischemic Encephalopathy (HIE) or preventing neonatal impairments due to antenatal/ post-natal injuries: preeclampsia, IntraUterineGrowthRestriction (IUGR), ventilation, Bronchopulmonary Dysplasia (BPD). ME has a good safety profile with no known adverse effects. This study aims to highlight that ME can prevent brain impairment due to premature birth. ME will be administered orally (3 mg/kg/die for 15 days to neonates born before 29+6 week gestation, in a prospective double blind, randomized vs placebo study, 2 parallel arms. ME and malondialdehyde (MDA), a lipid peroxidation product) levels before and at the end of treatment will be measured . Other outcomes: Cerebral ultrasounds (cUS); cerebral magnetic resonance imaging (cMRI), " Fagan test " eye tracking, ophthalmological, auditory, neurological/cognitive child assessments. Monitoring parental distress, which can influence the neurodevelopmental outcome in preterms.
Read the detailed description
About 552.000 infants are born in Italy each year, 1% of them with gestational age under 30 weeks. Survival rates are improved, but long-term disabilities are still common. Major destructive focal lesions became less common, the most predominant lesion at present is diffuse white matter (WM damage). The prevention of neurodevelopmental impairment is a major public health challenge and efforts are needed to test neuroprotective strategies. Melatonin (ME) serves as a neuroprotectant cerebral ischemia through its potent anti-oxidant/-inflammatory effect. Preclinical studies demonstrated that protects the developing brain by preventing abnormal myelination and inflammatory glial reaction. Clinical studies demonstrated ME ability in reducing brain damage after neonatal Hypoxic Ischemic Encephalopathy (HIE) or preventing neonatal impairments due to antenatal/ post-natal injuries: preeclampsia, IntraUterineGrowthRestriction (IUGR), ventilation, Bronchopulmonary Dysplasia (BPD). Ongoing studies are testing in premature neonates and pregnant women its neuroprotective properties. ME has a good safety profile with no known adverse effects.
This study aims to highlight that ME can prevent brain impairment due to premature birth. ME will be administered orally (3 mg/kg/die for 15 days within 96 hours from birth) to neonates born before 29+6 week gestation age (GA), in a prospective double blind, randomized vs placebo study, 2 parallel arms (30 preterm infants each). ME and malondialdehyde (MDA, a lipid peroxidation product) levels will be measured before and at the end of treatment. At birth, within 40 weeks of neonatal age, at 4-6 and at 24 months of age the following examinations are performed: Cerebral ultrasounds (cUS); cerebral magnetic resonance imaging (cMRI), during natural sleep (i.e. adopting sleep deprivation and/or feeding protocols); "Fagan test"eye tracking, ophthalmological, auditory brain stem evoked response (ABR), neurological/cognitive child assessments. Monitoring parental distress, which can influence the neurodevelopmental outcome in preterms.
- Conditions
- Malondialdehyde, Melatonin
- Being tested
- melatonin, placebo
- Keywords
- Preterm neonate, Neuroprotection, Malondialdehyde, Melatonin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
melatoninDietary supplement
Also called not reported
orally administered drops
placeboDrug
Also called not reported
orally administered drops
| Study group | Role | What they receive |
|---|---|---|
| melatonin | Experimental | melatonin oral drops; 3 mg/kg/day for 15 days Receives: Dietary Supplement: melatonin |
| placebo | Placebo comparator | oral drops manufactured to mimic melatonin Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Malondialdehyde
plasmatic concentration pg/ml
Measured: 15 days
Melatonin
plasmatic concentration pg/ml
Measured: 15 days
Secondary outcomes (3)
Cranial ultrasound (cUS) Assessment
to identify and score White Matter injuries
Measured: up to 40 weeks
Brain Magnetic Resonance Immaging (cMRI) Assessment
Identify and score White Matter injuries
Measured: up to 40 weeks
Auditory brain stem evoked response (ABR) Assessments
Identify and score auditory diseases
Measured: up to 40 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2020
- Study start25 May 2020
- Primary completion1 Oct 2022
- Study completion11 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for MalondialdehydeStudies 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 N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Francesca Garofoli
- Sponsor type
- University, hospital or other
- Collaborators
- IRCCS National Neurological Institute "C. Mondino" Foundation, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
- Responsible party
- Sponsor-investigator, Francesca Garofoli, Fondazione IRCCS Policlinico San Matteo di Pavia
- Investigators
- Chryssoula Tzialla, MD, Principal investigator, Fondazione IRCCS Policlinico San Matteo di Pavia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04235673
- Sponsor's protocol ID
- 20180004210 17/01/2018
- Status last verified
- Oct 2022
- First submitted
- 23 May 2019
- Last updated
- 25 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Garofoli F, Asteggiano C, Minniti ML, Accorsi P, Albertini R, Angelini M, Aversa S, Ballante E, Cabini RF, Caporali C, Cociglio S, Franco V, Longo S, Malerba L, Materia V, Mazzocchi L, Naboni C, Palmisani M, Pullega C, Pisoni C, Preda L, Riboli A, Risso FM, Rognone E, Savini G, Simoncelli AM, Villani P, Tzialla C, Pinelli L, Fazzi E, Chiapparini L, Borgatti R, Ghirardello S, Pichiecchio A, Orcesi S. Early Oral Melatonin Supplementation Supports White Matter Maturation in Preterm Infants: Neuroprotective Insights of an Antioxidant Molecule. J Pineal Res. 2026 May;78(3):e70147. doi: 10.1111/jpi.70147.
PubMed 42138165Garofoli F, Longo S, Pisoni C, Accorsi P, Angelini M, Aversa S, Caporali C, Cociglio S, De Silvestri A, Fazzi E, Rizzo V, Tzialla C, Zecca M, Orcesi S. Oral melatonin as a new tool for neuroprotection in preterm newborns: study protocol for a randomized controlled trial. Trials. 2021 Jan 22;22(1):82. doi: 10.1186/s13063-021-05034-w.
PubMed 33482894
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oral Melatonin as Neuroprotectant in Preterm Infants .A Prospective, Double Blind vs Placebo, Parallel Arms Study
- ClinicalTrials.gov ID
- NCT04235673
- Acronym / sponsor ID
- 20180004210 17/01/2018
- Conditions
- Malondialdehyde, Melatonin
- Keywords
- Preterm neonate, Neuroprotection, Malondialdehyde, Melatonin
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Francesca GarofoliUniversity, hospital or other
- Collaborators
- IRCCS National Neurological Institute "C. Mondino" Foundation, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
- Study start
- 25 May 2020 (actual)
- Primary completion
- 1 Oct 2022 (actual)
- Study completion
- 11 Oct 2022 (actual)
- First posted
- 22 Jan 2020 (actual)
- 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.
Preterm newborns survival rates are improved, but long-term disabilities are still common. Major destructive focal lesions became less common, the most predominant lesion at present is diffuse white matter (WM damage). Melatonin (ME) serves as a neuroprotectant cerebral ischemia through its potent anti-oxidant/-inflammatory effect. Preclinical studies demonstrated that protects the developing brain by preventing abnormal myelination and inflammatory glial reaction. Clinical studies demonstrated ME ability in reducing brain damage after neonatal Hypoxic Ischemic Encephalopathy (HIE) or preventing neonatal impairments due to antenatal/ post-natal injuries: preeclampsia, IntraUterineGrowthRestriction (IUGR), ventilation, Bronchopulmonary Dysplasia (BPD). ME has a good safety profile with no known adverse effects. This study aims to highlight that ME can prevent brain impairment due to premature birth. ME will be administered orally (3 mg/kg/die for 15 days to neonates born before 29+6 week gestation, in a prospective double blind, randomized vs placebo study, 2 parallel arms. ME and malondialdehyde (MDA), a lipid peroxidation product) levels before and at the end of treatment will be measured . Other outcomes: Cerebral ultrasounds (cUS); cerebral magnetic resonance imaging (cMRI), " Fagan test " eye tracking, ophthalmological, auditory, neurological/cognitive child assessments. Monitoring parental distress, which can influence the neurodevelopmental outcome in preterms.
Detailed description
About 552.000 infants are born in Italy each year, 1% of them with gestational age under 30 weeks. Survival rates are improved, but long-term disabilities are still common. Major destructive focal lesions became less common, the most predominant lesion at present is diffuse white matter (WM damage). The prevention of neurodevelopmental impairment is a major public health challenge and efforts are needed to test neuroprotective strategies. Melatonin (ME) serves as a neuroprotectant cerebral ischemia through its potent anti-oxidant/-inflammatory effect. Preclinical studies demonstrated that protects the developing brain by preventing abnormal myelination and inflammatory glial reaction. Clinical studies demonstrated ME ability in reducing brain damage after neonatal Hypoxic Ischemic Encephalopathy (HIE) or preventing neonatal impairments due to antenatal/ post-natal injuries: preeclampsia, IntraUterineGrowthRestriction (IUGR), ventilation, Bronchopulmonary Dysplasia (BPD). Ongoing studies are testing in premature neonates and pregnant women its neuroprotective properties. ME has a good safety profile with no known adverse effects.
This study aims to highlight that ME can prevent brain impairment due to premature birth. ME will be administered orally (3 mg/kg/die for 15 days within 96 hours from birth) to neonates born before 29+6 week gestation age (GA), in a prospective double blind, randomized vs placebo study, 2 parallel arms (30 preterm infants each). ME and malondialdehyde (MDA, a lipid peroxidation product) levels will be measured before and at the end of treatment. At birth, within 40 weeks of neonatal age, at 4-6 and at 24 months of age the following examinations are performed: Cerebral ultrasounds (cUS); cerebral magnetic resonance imaging (cMRI), during natural sleep (i.e. adopting sleep deprivation and/or feeding protocols); "Fagan test"eye tracking, ophthalmological, auditory brain stem evoked response (ABR), neurological/cognitive child assessments. Monitoring parental distress, which can influence the neurodevelopmental outcome in preterms.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| melatonin | Experimental | Dietary Supplement: melatoninmelatonin oral drops; 3 mg/kg/day for 15 days |
| placebo | Placebo comparator | Drug: placebooral drops manufactured to mimic melatonin |
Who may qualify
- Ages
- 25 to 30 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- preterm newborns gestational age GA < 29+6 weeks + day
- able to receive min 20ml/kg/day enteral nutrition, within 96 hours from birth
- written informed consent by both the parents.
Key exclusion criteria (5 listed)
- preterm newborns GA > 29+6 weeks + days
- not able to receive enteral nutrition (min 20 ml/kg/die) within 96 hours of life
- infants with genetic and/or congenital metabolic or chronic diseases
- intraventricular hemorrhage (IVH) ≥ III,
- parents refusing to sign a written informed consent
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 |
|---|---|---|
| melatoninAlso: not reportedorally administered drops | Dietary supplement | melatonin |
| placeboAlso: not reportedorally administered drops | Drug | placebo |
Primary outcome
Malondialdehyde
Time frame: 15 days
plasmatic concentration pg/ml
Melatonin
Time frame: 15 days
plasmatic concentration pg/ml
3 secondary outcomes
Cranial ultrasound (cUS) Assessment
Time frame: up to 40 weeks
Brain Magnetic Resonance Immaging (cMRI) Assessment
Time frame: up to 40 weeks
Auditory brain stem evoked response (ABR) Assessments
Time frame: up to 40 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2024.
- Derived from this study: PubMed 42138165Garofoli F, Asteggiano C, Minniti ML, Accorsi P, Albertini R, Angelini M, Aversa S, Ballante E, Cabini RF, Caporali C, Cociglio S, Franco V, Longo S, Malerba L, Materia V, Mazzocchi L, Naboni C, Palmisani M, Pullega C, Pisoni C, Preda L, Riboli A, Risso FM, Rognone E, Savini G, Simoncelli AM, Villani P, Tzialla C, Pinelli L, Fazzi E, Chiapparini L, Borgatti R, Ghirardello S, Pichiecchio A, Orcesi S. Early Oral Melatonin Supplementation Supports White Matter Maturation in Preterm Infants: Neuroprotective Insights of an Antioxidant Molecule. J Pineal Res. 2026 May;78(3):e70147. doi: 10.1111/jpi.70147.
- Derived from this study: PubMed 33482894Garofoli F, Longo S, Pisoni C, Accorsi P, Angelini M, Aversa S, Caporali C, Cociglio S, De Silvestri A, Fazzi E, Rizzo V, Tzialla C, Zecca M, Orcesi S. Oral melatonin as a new tool for neuroprotection in preterm newborns: study protocol for a randomized controlled trial. Trials. 2021 Jan 22;22(1):82. doi: 10.1186/s13063-021-05034-w.
- Individual participant dataSharing planned: No
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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.
Chryssoula Tzialla, MD principal investigator
Fondazione IRCCS Policlinico San Matteo di Pavia
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing melatonin in people with Malondialdehyde and Melatonin, run by Francesca Garofoli at 4 sites in Italy.
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 3 inclusion and 5 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: finished, as of the sponsor's last update on 25 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Italy. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Malondialdehyde (time frame: 15 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04235673, which also lists 2 linked publications.
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 25 Jul 2024.