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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
Sponsor:
Information provided by (Responsible Party):
Sudhin Thayyil, Thayyil, Sudhin

Study Description
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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.


Condition or disease
Neonatal Encephalopathy

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Study Design
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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
Groups and Cohorts
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Group/Cohort
HIE
Moderate of severe neonatal encephalopathy


Outcome Measures
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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Prognostic accuracy of [NAA] [ Time Frame: 18 months ]
    Assessed by BSID 3


Biospecimen Retention:   Samples With DNA
Blood and urine

Eligibility Criteria
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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

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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
Study Population
Healthy control infants, Infants with Neonatal encephalopathy, Healthy adult volunteers
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

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


Locations
United Kingdom
Sudhin Thayyil
London, United Kingdom
Sponsors and Collaborators
Thayyil, Sudhin
More Information
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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

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