Magnetic Resonance Biomarkers in Neonatal Encephalopathy (MARBLE)
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.
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||A Multicentre Prospective Study on Magnetic Resonance Biomarkers in Neonatal Encephalopathy|
- Prognostic accuracy of [NAA] [ Time Frame: 18 months ] [ Designated as safety issue: No ]Assessed by BSID 3
Biospecimen Retention: Samples With DNA
Blood and urine
|Study Start Date:||March 2011|
|Estimated Study Completion Date:||March 2016|
|Estimated Primary Completion Date:||March 2016 (Final data collection date for primary outcome measure)|
Moderate of severe neonatal encephalopathy
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01309711
|Contact: Sudhin Thayyil, PhDfirstname.lastname@example.org|
|London, United Kingdom|
|Contact: Sudhin Thayyil, PhD|