Inflammation and Metabolic Acidosis at Birth (AGAIN: AutophaGy AcIdosis Newborn)

NCT ID: NCT03897101

Last Updated: 2020-03-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

150 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-03-01

Study Completion Date

2020-12-31

Brief Summary

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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

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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

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Neonatal Encephalopathy Cell Damage Metabolic Acidosis Inflammation

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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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

No interventions assigned to this group

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

No interventions assigned to this group

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

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* suspected inborn errors of metabolism
* major chromosomal congenital defects
Minimum Eligible Age

15 Minutes

Maximum Eligible Age

6 Hours

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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AUSL Romagna Rimini

OTHER

Sponsor Role collaborator

University Hospital of Ferrara

OTHER

Sponsor Role lead

Responsible Party

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Anna Tarocco

Medical Doctor, Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Anna Tarocco, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital s. Anna Ferrara

Locations

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University Hospital "Sant'Anna" of Ferrara

Ferrara, , Italy

Site Status RECRUITING

Infermi Hospital Rimini

Rimini, , Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Anna Tarocco, MD

Role: CONTACT

+39 0532236014

Paolo Pinton, Prof

Role: CONTACT

0532455802

Facility Contacts

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Anna Tarocco, MD

Role: primary

+390532236014

Paolo Pinton, Prof

Role: backup

+390532455802

Gina Ancora, MD PhD

Role: primary

+390541705445

Miria Natile, MD

Role: backup

+390541705445

References

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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.

Reference Type BACKGROUND
PMID: 21138487 (View on PubMed)

Wang 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.

Reference Type BACKGROUND
PMID: 29681183 (View on PubMed)

Hassell 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.

Reference Type BACKGROUND
PMID: 26063194 (View on PubMed)

McAdams 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.

Reference Type BACKGROUND
PMID: 27524449 (View on PubMed)

Parikh 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.

Reference Type BACKGROUND
PMID: 29031859 (View on PubMed)

Martinello 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.

Reference Type BACKGROUND
PMID: 28389438 (View on PubMed)

Massaro 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.

Reference Type BACKGROUND
PMID: 29478510 (View on PubMed)

Prempunpong 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.

Reference Type BACKGROUND
PMID: 29095433 (View on PubMed)

Tarocco 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.

Reference Type DERIVED
PMID: 35551488 (View on PubMed)

Other Identifiers

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639/2018/Sper/AOUFe

Identifier Type: -

Identifier Source: org_study_id

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