Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting
Text Size

Magnetic Resonance Biomarkers in Neonatal Encephalopathy (MARBLE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2015 by Thayyil, Sudhin
Sponsor:
Information provided by (Responsible Party):
Sudhin Thayyil, Thayyil, Sudhin
ClinicalTrials.gov Identifier:
NCT01309711
First received: March 3, 2011
Last updated: November 2, 2015
Last verified: November 2015
History of Changes
  Purpose

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
Neonatal Encephalopathy

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Multicentre Prospective Study on Magnetic Resonance Biomarkers in Neonatal Encephalopathy

Resource links provided by NLM:

MedlinePlus related topics: Brain Diseases
U.S. FDA Resources

Further study details as provided by Thayyil, Sudhin:

Primary Outcome Measures:
  • 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

Estimated Enrollment: 180
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)
Groups/Cohorts
HIE
Moderate of severe neonatal encephalopathy

  Show Detailed Description

  Eligibility
Ages Eligible for Study:   up to 45 Years   (Child, Adult)
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01309711

Contacts
Contact: Sudhin Thayyil, PhD 00447912888700 s.thayyil@imperial.ac.uk

Locations
United Kingdom
Sudhin Thayyil Recruiting
London, United Kingdom
Contact: Sudhin Thayyil, PhD         
Sponsors and Collaborators
Thayyil, Sudhin
  More Information

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 
Study First Received: March 3, 2011
Last Updated: November 2, 2015
Health Authority: United Kingdom: National Institute for Health Research

Keywords provided by Thayyil, Sudhin:
MRI
Biomarkers
Neonatal encephalopathy
Therapeutic hypothermia

Additional relevant MeSH terms:
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on September 30, 2016