Magnetic Resonance Biomarkers in Neonatal Encephalopathy

NCT01309711 | Completed

• 1 other identifier: MARBLE
• Study Type: observational
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

N-acetylaspartate (NAA) is a surrogate neuronal marker and its proton magnetic resonance spectroscopy (1H MRS) signal decreases with increasing neuronal mortality associated with cerebral hypoxia-ischaemia. The MRS lactate (Lac)/NAA peak-area ratio increases during and after severe cerebral hypoxia-ischaemia reflecting mitochondrial injury and impaired oxidative phosphorylation. Aims: (1) To establish normative ranges for thalamic 1H MRS NAA concentration and Lac/NAA in healthy newborn infants (2) To examine the accuracies of thalamic 1H MRS NAA concentration and Lac/NAA for predicting adverse neurodevelopmental outcome in neonatal encephalopathy (NE) Design: Prospective observational study Methods: Year 1: Following 1H MRS methodology optimisation 40 healthy control infants will be recruited to collect normative data. Year 2 to 3: 115 infants with NE, undergoing therapeutic hypothermia will be recruited. MRS will be performed aged less than 4 days and 7 to 14 days and thalamic NAA levels and Lac/NAA will be quantified; Qualitative interviews to evaluate parental understanding of this biomarker. Year 4, 5: Outcome assessment by BSID III at 18 months. Outcomes: Mean thalamic NAA levels and Lac/NAA and appropriate confidence intervals in normal infants, and thalamic NAA levels and Lac/NAA in infants with NE according to neurodevelopmental outcome. Areas under curves for thalamic NAA and Lac/NAA will be examined separately for early \& late MRS. Accuracy of early MRS will inform utility of this investigation in decisions about withdrawal of life support; late MRS will inform about efficacy as a surrogate end point in clinical trials. Qualitative interviews will be thematically analysed and reported.

Conditions

Neonatal Encephalopathy

Keywords

MRI; Biomarkers; Neonatal encephalopathy; Therapeutic hypothermia

Outcome Measures

Primary Outcomes (1)

• Prognostic accuracy of [NAA]

  Assessed by BSID 3

  18 months

Study Arms (1)

HIE

Moderate of severe neonatal encephalopathy

Eligibility Criteria

• Age: 1 Day - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Healthy control infants, Infants with Neonatal encephalopathy, Healthy adult volunteers

You may qualify if:

• Group I (Controls): Healthy newborn infants (gestation 36 to 43 weeks, birth weight \>2.7 kg)
• Group II (NE): Infants 36 to 43 weeks gestation with at least one of the following:
• Evidence of perinatal asphyxia as indicated by
• Apgar score of \<5 at 5 minutes after birth
• Continued need for resuscitation, including endotracheal or mask ventilation, at 5 minutes after birth
• Acidosis defined as pH \<7.00 and/or base deficit \>16 mmol/L in umbilical cord blood sample or any blood sample within 60 minutes of birth (arterial or venous blood) AND
• Moderate to severe encephalopathy consisting of altered state of consciousness (reduced or absent response to stimulation) and hypotonia, and abnormal primitive reflexes (weak or absent suck or Moro response). Clinical NE severity will be assessed by Thompson encephalopathy score.
• Group III (Healthy adult volunteers): Same individual will be scanned multiple times at each of the centres to examine intra and inter-centre variability of thalamic \[NAA\].

You may not qualify if:

• Life threatening congenital malformations
• Syndromic infants
• Metabolic disorders
• Meningitis or encephalitis

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

Sudhin Thayyil

London, United Kingdom

Location

Related Publications (3)

• Lally PJ, Pauliah S, Montaldo P, Chaban B, Oliveira V, Bainbridge A, Soe A, Pattnayak S, Clarke P, Satodia P, Harigopal S, Abernethy LJ, Turner MA, Huertas-Ceballos A, Shankaran S, Thayyil S. Magnetic Resonance Biomarkers in Neonatal Encephalopathy (MARBLE): a prospective multicountry study. BMJ Open. 2015 Sep 30;5(9):e008912. doi: 10.1136/bmjopen-2015-008912.

  PMID: 26423856 BACKGROUND

• Lally PJ, Montaldo P, Oliveira V, Soe A, Swamy R, Bassett P, Mendoza J, Atreja G, Kariholu U, Pattnayak S, Sashikumar P, Harizaj H, Mitchell M, Ganesh V, Harigopal S, Dixon J, English P, Clarke P, Muthukumar P, Satodia P, Wayte S, Abernethy LJ, Yajamanyam K, Bainbridge A, Price D, Huertas A, Sharp DJ, Kalra V, Chawla S, Shankaran S, Thayyil S; MARBLE consortium. Magnetic resonance spectroscopy assessment of brain injury after moderate hypothermia in neonatal encephalopathy: a prospective multicentre cohort study. Lancet Neurol. 2019 Jan;18(1):35-45. doi: 10.1016/S1474-4422(18)30325-9. Epub 2018 Nov 15.

  PMID: 30447969 DERIVED

• Lally PJ, Montaldo P, Oliveira V, Swamy RS, Soe A, Shankaran S, Thayyil S. Residual brain injury after early discontinuation of cooling therapy in mild neonatal encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2018 Jul;103(4):F383-F387. doi: 10.1136/archdischild-2017-313321. Epub 2017 Sep 21.

  PMID: 28935718 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood and urine

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2011
• First Posted: March 7, 2011
• Study Start: March 30, 2011
• Primary Completion: August 13, 2017
• Study Completion: December 31, 2017
• Last Updated: March 19, 2024

Record last verified: 2024-03

Locations

GB (1)