NCT01309711: MARBLE

Magnetic Resonance Biomarkers in Neonatal Encephalopathy

Completed Last updated 19 March 2024

What this trial tests

trial in Neonatal Encephalopathy in 180 participants. Completed in 31 December 2017.

Timeline

30 March 2011

Primary endpoint
13 August 2017

31 December 2017

Quick facts

Lead sponsor	Imperial College London
Status	Completed
Study type	OBSERVATIONAL
Enrollment	180
Start date	30 March 2011
Primary completion	13 August 2017
Estimated completion	31 December 2017
Sites	1 location across United Kingdom

Conditions studied

• Neonatal Encephalopathy — all drugs for Neonatal Encephalopathy →

Sponsor

Imperial College London

Who can join

Adults 1 Day to 45, any sex, with Neonatal Encephalopathy. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. Magnetic resonance spectroscopy assessment of brain injury after moderate hypothermia in neonatal encephalopathy: a prospective multicentre cohort study.
   Lally PJ, Montaldo P, Oliveira V, Soe A, et al · · 2019 · cited 156× · PMID 30447969 · DOI 10.1016/s1474-4422(18)30325-9
2. Residual brain injury after early discontinuation of cooling therapy in mild neonatal encephalopathy.
   Lally PJ, Montaldo P, Oliveira V, Swamy RS, et al · · 2018 · cited 22× · PMID 28935718 · DOI 10.1136/archdischild-2017-313321
3. Magnetic Resonance Biomarkers in Neonatal Encephalopathy (MARBLE): a prospective multicountry study.
   Lally PJ, Pauliah S, Montaldo P, Chaban B, et al · · 2015 · cited 17× · PMID 26423856 · DOI 10.1136/bmjopen-2015-008912
4. White matter injury after neonatal encephalopathy is associated with thalamic metabolite perturbations.
   Montaldo P, Ivain P, Lally P, Bassett P, et al · · 2020 · cited 8× · PMID 32062359 · DOI 10.1016/j.ebiom.2020.102663
5. Identifying the translational complexity of magnetic resonance spectroscopy in neonates and infants.
   Moss HG, Jenkins DD, Yazdani M, Brown TR. · · 2019 · cited 8× · PMID 30924565 · DOI 10.1002/nbm.4089