Neonatal EncephalopathyAGAINNCT03897101
Inflammation and Metabolic Acidosis at Birth (AGAIN: AutophaGy AcIdosis Newborn)
An observational study of Neonatal Encephalopathy and Cell Damage, run by University Hospital of Ferrara at 2 sites in Italy.
Trial summary
Protection of brain development is a major aim in the Neonatal Intensive Care Unit. Neonatal encephalopathy (NE) occurs in 1.8 to 7.7 infants per 1000 births. Over the last six years, several randomized control trials have demonstrated that therapeutic hypothermia reduces the rate of death or disability at 18 months… Read more about this study
- Who is it for?
- Ages 15 minutes to 6 hoursHealthy volunteers can take part
- Conditions the study is for
- Neonatal Encephalopathy, Cell Damage, Metabolic Acidosis
- How many people
- 150 participants
- Where
- 2 sitesItaly
- Study dates
- 1 Mar 2019to 31 Dec 2020
- How long will I take part?
- 7 Days
- Phase
- Observational
- 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 15 minutes to 6 hours
- All sexes
- Healthy volunteers accepted
- Child
Study population: will be recruited 50 newborns with mild neonatal encephalopathy and metabolic acidosis at birth not qualified for therapeutic hypothermia
Who may be able to join
- gestational age > 35 weeks and weight > 1800 gr
- Apgar score < 5 at 10 minutes o need for cardiopulmonary resuscitation at 10 minutes or evidence of base excess > 12 mmol/L or pH < 7,0 at initial blood gas analyses
- evidence of mild encephalopathy graded according to Sarnat\&Sarnat neurological evaluation
- normal amplitude integrated electroencephalography
Who cannot join
- suspected inborn errors of metabolism
- major chromosomal congenital defects
Trial locations and contacts
2 sites in 1 country.
Italy2 sites, 2 recruiting
- Recruiting
University Hospital "Sant'Anna" of Ferrara
Ferrara, 44124
Anna Tarocco, MD, +390532236014, anna.tarocco@unife.it
Paolo Pinton, Prof, +390532455802, paolo.pinton@unife.it
- Recruiting
Infermi Hospital Rimini
Rimini, 47923
Gina Ancora, MD PhD, +390541705445, gina.ancora@auslromagna.it
Miria Natile, MD, +390541705445, mirianatile@gmail.com
About this study
Official title: Autophagy, Mitophagy, Inflammation and Plasmatic Concentration of Melatonin in Newborn With Metabolic Acidosis at Birth
Protection of brain development is a major aim in the Neonatal Intensive Care Unit. Neonatal encephalopathy (NE) occurs in 1.8 to 7.7 infants per 1000 births. Over the last six years, several randomized control trials have demonstrated that therapeutic hypothermia reduces the rate of death or disability at 18 months of age among infants who survived. However, the neurodevelopmental outcome in milder NE not treated with hypothermia remains unclear.
A multicenter prospective observational study will be conducted to determine biological changes of mild neonatal encephalopathy who are not recruited for therapeutic hypothermia .
Read the detailed description
It is a prospective observational multicenter study on 50 newborns with mild neonatal encephalopathy and metabolic acidosis at birth not qualified for therapeutic hypothermia compared to healthy controls.
Infants with metabolic acidosis at birth and evidence of mild encephalopathy graded according to Sarnat\&Sarnat neurological evaluation will be recruited to evaluate plasma concentration of melatonin and levels of Autophagy, mitophagy and inflammation.
Plasmatic changes will be compared to:
- healthy control
- infants with isolated metabolic acidosis at birth and normal neurological evaluation.
- Conditions
- Neonatal Encephalopathy, Cell Damage, Metabolic Acidosis, Inflammation
- Keywords
- mild neonatal encephalopathy, birth asphyxia, metabolic acidosis, Autophagy, Mitophagy, inflammation
- Medical subject headings
- Acidosis, Inflammation, Asphyxia Neonatorum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| MILD NE | gestational age > 35 weeks and weight > 1800 gr * Apgar score < 5 at 10 minutes o need for cardiopulmonary resuscitation at 10 minutes or evidence of base excess > 12 mmol/L or pH < 7,0 at initial blood gas analyses * evidence of mild encephalopathy graded according to Sarnat\&Sarnat neurological evaluation * normal amplitude integrated electroencephalography Plasma levels of melatonin, Atg5, Parkin, Pink1, inflammatory cytokines will be evaluated | |
| ISOLATED METABOLIC ACIDOSIS | gestational age > 35 weeks and weight > 1800 gr * evidence of base excess > 12 mmol/L or pH < 7,0 at initial blood gas analyses * Normal Sarnat\&Sarnat neurological evaluation Plasma levels of melatonin, Atg5, Parkin, Pink1, inflammatory cytokines will be evaluated | |
| HEALTY CONTROLS | gestational age > 35 weeks and weight > 1800 gr Normal blood pH or base excess Plasma levels of melatonin, Atg5, Parkin, Pink1, inflammatory cytokiness will be evaluated |
What is being measured
The primary outcome is the main question the study is designed to answer.
change from baseline ATG5 Plasma concentration at 7 days of life
correlation between metabolic acidosis at birth and Autophagy. ELISA test will be used to measure plasma levels of ATG5
Measured: birth, 72 hours, 7 days of life
Secondary outcomes (1)
change from baseline Parkin and Pink1 Plasma concentration at 7 days of life
correlation between metabolic acidosis at birth and Mitophagy. ELISA test will be used to measure plasma levels of Parkin and Park1
Measured: birth, 72 hours, 7 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 posted1 Apr 2019
- Study start1 Mar 2019
- Primary completion31 Dec 2019
- Study completion31 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Neonatal 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 150 participants (estimated)
- Target duration
- 7 Days
Sponsor and investigators
- Lead sponsor
- University Hospital of Ferrara
- Sponsor type
- University, hospital or other
- Collaborators
- AUSL Romagna Rimini
- Responsible party
- Principal investigator, Anna Tarocco, University Hospital of Ferrara
- Investigators
- Anna Tarocco, MD, Principal investigator, University Hospital s. Anna Ferrara
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03897101
- Sponsor's protocol ID
- 639/2018/Sper/AOUFe
- Acronym
- AGAIN
- Status last verified
- Mar 2020
- First submitted
- 27 Mar 2019
- Last updated
- 25 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Alirezaei M, Kemball CC, Whitton JL. Autophagy, inflammation and neurodegenerative disease. Eur J Neurosci. 2011 Jan;33(2):197-204. doi: 10.1111/j.1460-9568.2010.07500.x. Epub 2010 Dec 7.
PubMed 21138487Wang 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.
PubMed 29681183Hassell 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.
PubMed 26063194McAdams 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.
PubMed 27524449Parikh 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.
PubMed 29031859Martinello 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.
PubMed 28389438Massaro AN, Wu YW, Bammler TK, Comstock B, Mathur A, McKinstry RC, Chang T, Mayock DE, Mulkey SB, Van Meurs K, Juul S. Plasma Biomarkers of Brain Injury in Neonatal Hypoxic-Ischemic Encephalopathy. J Pediatr. 2018 Mar;194:67-75.e1. doi: 10.1016/j.jpeds.2017.10.060.
PubMed 29478510Prempunpong C, Chalak LF, Garfinkle J, Shah B, Kalra V, Rollins N, Boyle R, Nguyen KA, Mir I, Pappas A, Montaldo P, Thayyil S, Sanchez PJ, Shankaran S, Laptook AR, Sant'Anna G. Prospective research on infants with mild encephalopathy: the PRIME study. J Perinatol. 2018 Jan;38(1):80-85. doi: 10.1038/jp.2017.164. Epub 2017 Nov 2.
PubMed 29095433Tarocco A, Morciano G, Perrone M, Cafolla C, Ferre C, Vacca T, Pistocchi G, Meneghin F, Cocchi I, Lista G, Cetin I, Greco P, Garani G, Stella M, Natile M, Ancora G, Savarese I, Campi F, Bersani I, Dotta A, Tiberi E, Vento G, Chiodin E, Staffler A, Maranella E, Di Fabio S, Wieckowski MR, Giorgi C, Pinton P. Increase of Parkin and ATG5 plasmatic levels following perinatal hypoxic-ischemic encephalopathy. Sci Rep. 2022 May 12;12(1):7795. doi: 10.1038/s41598-022-11870-w.
PubMed 35551488
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Autophagy, Mitophagy, Inflammation and Plasmatic Concentration of Melatonin in Newborn With Metabolic Acidosis at Birth
- ClinicalTrials.gov ID
- NCT03897101
- Acronym / sponsor ID
- AGAIN / 639/2018/Sper/AOUFe
- Conditions
- Neonatal Encephalopathy, Cell Damage, Metabolic Acidosis, Inflammation
- Keywords
- mild neonatal encephalopathy, birth asphyxia, metabolic acidosis, Autophagy, Mitophagy, inflammation
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- University Hospital of FerraraUniversity, hospital or other
- Collaborators
- AUSL Romagna Rimini
- Study start
- 1 Mar 2019 (actual)
- Primary completion
- 31 Dec 2019 (actual)
- Study completion
- 31 Dec 2020 (estimated)
- First posted
- 1 Apr 2019 (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.
Protection of brain development is a major aim in the Neonatal Intensive Care Unit. Neonatal encephalopathy (NE) occurs in 1.8 to 7.7 infants per 1000 births. Over the last six years, several randomized control trials have demonstrated that therapeutic hypothermia reduces the rate of death or disability at 18 months of age among infants who survived. However, the neurodevelopmental outcome in milder NE not treated with hypothermia remains unclear.
A multicenter prospective observational study will be conducted to determine biological changes of mild neonatal encephalopathy who are not recruited for therapeutic hypothermia .
Detailed description
It is a prospective observational multicenter study on 50 newborns with mild neonatal encephalopathy and metabolic acidosis at birth not qualified for therapeutic hypothermia compared to healthy controls.
Infants with metabolic acidosis at birth and evidence of mild encephalopathy graded according to Sarnat\&Sarnat neurological evaluation will be recruited to evaluate plasma concentration of melatonin and levels of Autophagy, mitophagy and inflammation.
Plasmatic changes will be compared to:
- healthy control
- infants with isolated metabolic acidosis at birth and normal neurological evaluation.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Target follow-up
- 7 Days
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| MILD NE | – | –gestational age > 35 weeks and weight > 1800 gr * Apgar score < 5 at 10 minutes o need for cardiopulmonary resuscitation at 10 minutes or evidence of base excess > 12 mmol/L or pH < 7,0 at initial blood gas analyses * evidence of mild encephalopathy graded according to Sarnat\&Sarnat neurological evaluation * normal amplitude integrated electroencephalography Plasma levels of melatonin, Atg5, Parkin, Pink1, inflammatory cytokines will be evaluated |
| ISOLATED METABOLIC ACIDOSIS | – | –gestational age > 35 weeks and weight > 1800 gr * evidence of base excess > 12 mmol/L or pH < 7,0 at initial blood gas analyses * Normal Sarnat\&Sarnat neurological evaluation Plasma levels of melatonin, Atg5, Parkin, Pink1, inflammatory cytokines will be evaluated |
| HEALTY CONTROLS | – | –gestational age > 35 weeks and weight > 1800 gr Normal blood pH or base excess Plasma levels of melatonin, Atg5, Parkin, Pink1, inflammatory cytokiness will be evaluated |
Who may qualify
- Ages
- 15 minutes to 6 hours
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- will be recruited 50 newborns with mild neonatal encephalopathy and metabolic acidosis at birth not qualified for therapeutic hypothermia
Key inclusion criteria (4 listed)
- gestational age > 35 weeks and weight > 1800 gr
- Apgar score < 5 at 10 minutes o need for cardiopulmonary resuscitation at 10 minutes or evidence of base excess > 12 mmol/L or pH < 7,0 at initial blood gas analyses
- evidence of mild encephalopathy graded according to Sarnat\&Sarnat neurological evaluation
- normal amplitude integrated electroencephalography
Key exclusion criteria (2 listed)
- suspected inborn errors of metabolism
- major chromosomal 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.
Primary outcome
change from baseline ATG5 Plasma concentration at 7 days of life
Time frame: birth, 72 hours, 7 days of life
correlation between metabolic acidosis at birth and Autophagy. ELISA test will be used to measure plasma levels of ATG5
1 secondary outcome
change from baseline Parkin and Pink1 Plasma concentration at 7 days of life
Time frame: birth, 72 hours, 7 days of life
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2020.
- Background: PubMed 21138487Alirezaei M, Kemball CC, Whitton JL. Autophagy, inflammation and neurodegenerative disease. Eur J Neurosci. 2011 Jan;33(2):197-204. doi: 10.1111/j.1460-9568.2010.07500.x. Epub 2010 Dec 7.
- Background: PubMed 29681183Wang 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.
- Background: PubMed 26063194Hassell 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.
- Background: PubMed 27524449McAdams 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.
- Background: PubMed 29031859Parikh 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.
- Background: PubMed 28389438Martinello 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.
- Background: PubMed 29478510Massaro AN, Wu YW, Bammler TK, Comstock B, Mathur A, McKinstry RC, Chang T, Mayock DE, Mulkey SB, Van Meurs K, Juul S. Plasma Biomarkers of Brain Injury in Neonatal Hypoxic-Ischemic Encephalopathy. J Pediatr. 2018 Mar;194:67-75.e1. doi: 10.1016/j.jpeds.2017.10.060.
- Background: PubMed 29095433Prempunpong C, Chalak LF, Garfinkle J, Shah B, Kalra V, Rollins N, Boyle R, Nguyen KA, Mir I, Pappas A, Montaldo P, Thayyil S, Sanchez PJ, Shankaran S, Laptook AR, Sant'Anna G. Prospective research on infants with mild encephalopathy: the PRIME study. J Perinatol. 2018 Jan;38(1):80-85. doi: 10.1038/jp.2017.164. Epub 2017 Nov 2.
- Derived from this study: PubMed 35551488Tarocco A, Morciano G, Perrone M, Cafolla C, Ferre C, Vacca T, Pistocchi G, Meneghin F, Cocchi I, Lista G, Cetin I, Greco P, Garani G, Stella M, Natile M, Ancora G, Savarese I, Campi F, Bersani I, Dotta A, Tiberi E, Vento G, Chiodin E, Staffler A, Maranella E, Di Fabio S, Wieckowski MR, Giorgi C, Pinton P. Increase of Parkin and ATG5 plasmatic levels following perinatal hypoxic-ischemic encephalopathy. Sci Rep. 2022 May 12;12(1):7795. doi: 10.1038/s41598-022-11870-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.
Anna Tarocco, MD principal investigator
University Hospital s. Anna Ferrara
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Neonatal Encephalopathy and Cell Damage, run by University Hospital of Ferrara at 2 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 4 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 25 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Anna Tarocco, MD (+39 0532236014, anna.tarocco@unife.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
change from baseline ATG5 Plasma concentration at 7 days of life (time frame: birth, 72 hours, 7 days of life). 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 NCT03897101, which also lists 9 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 Mar 2020.