Clinical trial NCT03897101: Inflammation and Metabolic Acidosis at Birth (AGAIN: AutophaGy AcIdosis Newborn)
Official title: Autophagy, Mitophagy, Inflammation and Plasmatic Concentration of Melatonin in Newborn With Metabolic Acidosis at Birth
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Neonatal Encephalopathy
Cell Damage
Metabolic Acidosis
Inflammation
Keywords: mild neonatal encephalopathy
birth asphyxia
metabolic acidosis
Autophagy
Mitophagy
inflammation
Lead sponsor: University Hospital of Ferrara
Sponsor class: OTHER
Collaborators: name: AUSL Romagna Rimini
First posted: 2019-04-01
Enrollment: 150
Sex: ALL
Minimum age (years): 15
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: will be recruited 50 newborns with mild neonatal encephalopathy and metabolic acidosis at birth not qualified for therapeutic hypothermia

Brief 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 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.

Eligibility criteria: 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

Primary outcomes:
measure: change from baseline ATG5 Plasma concentration at 7 days of life
timeFrame: birth, 72 hours, 7 days of life
Secondary outcomes:
measure: change from baseline Parkin and Pink1 Plasma concentration at 7 days of life
timeFrame: birth, 72 hours, 7 days of life
Other outcomes:
measure: change from baseline Plasma Concentration of Melatonin at 7 days of life
timeFrame: birth, 72 hours, 7 days of life
measure: change from baseline of inflammatory cytokines at 7 days of life
timeFrame: birth, 72 hours, 7 days of life
Locations:
city: Ferrara
country: Italy
facility: University Hospital "Sant'Anna" of Ferrara
city: Rimini
country: Italy
facility: Infermi Hospital Rimini
Study officials:
affiliation: University Hospital s. Anna Ferrara
name: Anna Tarocco, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
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citation: 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.
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citation: 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.
citation: 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.
citation: 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.