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

Inflammation Clinical Trial

— AGAIN  

Official title:

Autophagy, Mitophagy, Inflammation and Plasmatic Concentration of Melatonin in Newborn With Metabolic Acidosis at Birth

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03897101
• Other study ID #: 639/2018/Sper/AOUFe
• Status: Recruiting
• Start date: March 1, 2019
• Est. completion date: December 31, 2020

Study information

• Verified date: March 2020
• Source: University Hospital of Ferrara
• Contact: Anna Tarocco, MD
• Phone: +39 0532236014
• Email: anna.tarocco[@]unife.it
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical 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 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 .

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 6 Hours

Eligibility

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

Related Conditions & MeSH terms

• Acidosis
• Brain Diseases
• Cell Damage
• Inflammation
• Metabolic Acidosis
• Neonatal Encephalopathy

Locations

Country	Name	City	State
Italy	University Hospital "Sant'Anna" of Ferrara	Ferrara
Italy	Infermi Hospital Rimini	Rimini

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital of Ferrara	AUSL Romagna Rimini

Country where clinical trial is conducted

Italy, 

References & Publications (8)

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. Review. — View Citation

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. Review. — View Citation

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. — View 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. — View Citation

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. Review. — View 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. — View 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, Sánchez 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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	change from baseline Plasma Concentration of Melatonin at 7 days of life	UPLC-Massa Acquity-Xevo TQD (Waters) will be used to measure plasma melatonin concentration.	birth, 72 hours, 7 days of life
Other	change from baseline of inflammatory cytokines at 7 days of life	correlation between metabolic acidosis at birth and inflammatory cytokines. ELISA test will be used to measure plasma levels inflammatory cytokines.	birth, 72 hours, 7 days of life
Primary	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	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	birth, 72 hours, 7 days of life