Lipoma of Spinal Cord Clinical Trial
Official title:
Developing a Biomarker for Monitoring Clinical Outcomes in Children With Spinal Lipoma
'Spinal lipoma' is a condition, present from before birth, in which fatty tissue (lipoma) is attached to the lower end of the spinal cord, tethering it within the vertebral canal. The cord normally moves up and down with respiration, whereas tethering prevents this movement, and can lead to progressive neurological deterioration. The cord and spinal nerves become stretched and their blood supply is damaged irreversibly. Disability may include weakness or pain in the lower body, and urinary disorders in young children. Treatment is surgical, to remove the lipoma and mobilise the spinal cord, with 60 such operations performed per year at Great Ormond Street Hospital. This project aims to develop lipidomic biomarkers in order to predict which children with spinal lipoma are at highest risk of neurological deterioration, and require early surgery, while providing evidence to adopt a more conservative approach for those at lower risk.
Clinical study to seek a metabolic biomarker(s), detectable by mass spectrometry, that can
be used to 'stratify' patients with asymptomatic lipoma. In view of the often extensive
nature of lipomas associated with the low spinal cord, we hypothesise that lipid components,
or metabolites derived from them, may gain entry to the child's bloodstream. The more
infiltrative lipomas carry a higher risk of symptomatic deterioration and, we argue, should
also have a higher chance of generating a lipid 'signature' in the blood and/or urine. Phase
1 ‐ Cerebrospinal fluid, blood and urine samples will be obtained from patients with spinal
lipoma undergoing surgery (n = 3 to 5). Informed consent, following appropriate ethics
committee approval, will be implemented. Blood and urine will be sampled pre‐operatively,
and intra‐operative cerebrospinal fluid samples will be obtained. Mass spectrometry analysis
will identify lipid species present in the cerebrospinal fluid of these patients, and the
extent to which these are also detectable in the patient's blood and/or urine. Any lipid
species detected in both cerebrospinal fluid and blood/urine will represent potential
biomarkers, and will form the focus of the next phase of the study. Phase 2 will then assess
the discriminatory value of these potential biomarkers by comparing their profiles in blood
and/or urine from three clinical groups: (i) Patients with spinal lipomas who have
neurological symptoms/signs, and are attending hospital for surgery (i.e. similar patients
as in Phase 1). Blood/urine samples will be taken preoperatively, to represent the 'high
risk' group. (ii) Patients with spinal lipomas who have remained asymptomatic after several
years follow‐up.
These represent the 'low risk' group; (iii) Patients with spinal conditions not involving
lipoma. These represent our 'negative' control group. Group sizes will be determined by
power calculations using variance data from the patient measurements in Phase 1. Statistical
analysis will be by 1‐way ANOVA, or non‐parametric equivalent, to test for significant
differences between the three groups. Mass spectrometry (Figure 2) will be performed in the
Institute of Child Health Centre for Proteomics, Metabolomics and Lipidomics using nano
ultra performance liquid chromatography and ultra performance convergence chromatography -
quadrupole time of flight mass spectrometry, a new mass spectral technology for lipidomic
and metabolomic analysis. Ultra performance convergence chromatography is a chromatography
technology that uses carbon dioxide present in a super critical fluid state as a mobile
phase and allows the fractionation of metabolites and lipids according to their class and
not hydrophobicity. It enables quantitation of all the major lipid classes present in a
tissue including phospholipids, free fatty acids, esterified fatty acids, cholesterol esters
and sterols. Non‐lipid molecules (e.g. choline) might also show altered abundance in lipoma
patients and so a more general metabolomics analysis will also be undertaken, if time
permits.
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Observational Model: Cohort, Time Perspective: Prospective