Magnetic Resonance Biomarkers in Neonatal Encephalopathy (MARBLE)
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ClinicalTrials.gov Identifier: NCT01309711 |
Recruitment Status
:
Completed
First Posted
: March 7, 2011
Last Update Posted
: January 12, 2018
|
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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.
Condition or disease |
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Neonatal Encephalopathy |

Study Type : | Observational |
Estimated Enrollment : | 180 participants |
Observational Model: | Cohort |
Time Perspective: | Prospective |
Official Title: | A Multicentre Prospective Study on Magnetic Resonance Biomarkers in Neonatal Encephalopathy |
Actual Study Start Date : | March 30, 2011 |
Actual Primary Completion Date : | August 13, 2017 |
Actual Study Completion Date : | December 31, 2017 |
Group/Cohort |
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HIE
Moderate of severe neonatal encephalopathy
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- Prognostic accuracy of [NAA] [ Time Frame: 18 months ]Assessed by BSID 3
Biospecimen Retention: Samples With DNA

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Ages Eligible for Study: | up to 45 Years (Child, Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
Sampling Method: | Non-Probability Sample |
Inclusion Criteria:
- 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].
Exclusion Criteria:
- Life threatening congenital malformations
- Syndromic infants
- Metabolic disorders
- Meningitis or encephalitis

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01309711
United Kingdom | |
Sudhin Thayyil | |
London, United Kingdom |
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Sudhin Thayyil, Consultant Neonatologist, Thayyil, Sudhin |
ClinicalTrials.gov Identifier: | NCT01309711 History of Changes |
Other Study ID Numbers: |
MARBLE |
First Posted: | March 7, 2011 Key Record Dates |
Last Update Posted: | January 12, 2018 |
Last Verified: | January 2018 |
Keywords provided by Sudhin Thayyil, Thayyil, Sudhin:
MRI Biomarkers Neonatal encephalopathy Therapeutic hypothermia |
Additional relevant MeSH terms:
Brain Diseases Central Nervous System Diseases Nervous System Diseases |