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

NCT03897101 | Unknown DMC

• 1 other identifier: 639/2018/Sper/AOUFe
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 2

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 .

Conditions

Neonatal Encephalopathy; Cell Damage; Metabolic Acidosis; Inflammation

Keywords

mild neonatal encephalopathy; birth asphyxia; metabolic acidosis; Autophagy; Mitophagy; inflammation

Outcome Measures

Primary Outcomes (1)

• 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

  birth, 72 hours, 7 days of life

Secondary Outcomes (1)

• change from baseline Parkin and Pink1 Plasma concentration at 7 days of life

  birth, 72 hours, 7 days of life

Other Outcomes (2)

• change from baseline Plasma Concentration of Melatonin at 7 days of life

  birth, 72 hours, 7 days of life

• change from baseline of inflammatory cytokines at 7 days of life

  birth, 72 hours, 7 days of life

Study Arms (3)

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

Eligibility Criteria

• Age: 15 Minutes - 6 Hours
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• 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

You may qualify if:

• 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

You may not qualify if:

• suspected inborn errors of metabolism
• major chromosomal congenital defects

Sponsors & Collaborators

• University Hospital of Ferrara: lead
• AUSL Romagna Rimini: collaborator

Study Sites (2)

University Hospital "Sant'Anna" of Ferrara

Ferrara, 44124, Italy

RECRUITING

Infermi Hospital Rimini

Rimini, 47923, Italy

RECRUITING

Related Publications (9)

• 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.

  PMID: 21138487 BACKGROUND

• 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.

  PMID: 29681183 BACKGROUND

• 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.

  PMID: 26063194 BACKGROUND

• 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.

  PMID: 27524449 BACKGROUND

• 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.

  PMID: 29031859 BACKGROUND

• 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.

  PMID: 28389438 BACKGROUND

• 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.

  PMID: 29478510 BACKGROUND

• 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.

  PMID: 29095433 BACKGROUND

• 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.

  PMID: 35551488 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

plasma

MeSH Terms

Conditions

Acidosis; Inflammation; Asphyxia Neonatorum

Condition Hierarchy (Ancestors)

Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Anna Tarocco, MD

  University Hospital s. Anna Ferrara

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anna Tarocco, MD

CONTACT

+39 0532236014; anna.tarocco@unife.it

Paolo Pinton, Prof

CONTACT

0532455802; paolo.pinton@unife.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 7 Days
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor, Principal Investigator

Study Record Dates

• First Submitted: March 27, 2019
• First Posted: April 1, 2019
• Study Start: March 1, 2019
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2020
• Last Updated: March 25, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)