Creation and validation of biomarkers in inflammatory neuropathies
Research type
Research Study
Full title
A pilot study to develop and validate biomarkers to monitor disease progression in POEMS syndrome and inflammatory neuropathies using a disability scale designed using Rasch statistics and magnetic resonance imaging
IRAS ID
289324
Contact name
Michael PT Lunn
Contact email
Sponsor organisation
University College London
Clinicaltrials.gov Identifier
Z6364106/2021/05/201 , UCL DPN
Duration of Study in the UK
5 years, 7 months, 1 days
Research summary
The inflammatory neuropathies are a group of conditions where nerve damage is due to direct attack by the body’s own immune system. There are very few serological biomarkers to aid with diagnosis, prognostication or treatment response. Rasch-built overall disability scales (RODS) have been designed which allow for a quantitative measurement of patient-reported disability, but importantly the scales are condition-specific. In the rare POEMS syndrome, the blood biomarker Vascular Endothelial Growth Factor (VEGF) is a highly sensitive for diagnosis but is less reflective of disease activity.
We will attempt to identify effective non-invasive biomarkers in two modalities, investigating whether patient-reported outcome measures and magnetic resonance imaging (MRI) are effective as biomarkers in POEMS syndrome and other inflammatory neuropathies:
a) We will design and validate a Rasch-built overall disability scale (RODS) specific to POEMS neuropathy. A preliminary RODS will be created and tested using a cohort of patients from the United Kingdom's national POEMS service, led by the Neuromuscular team at UCLH. After removal of poorly fitting items, and elements unreflective of disease-related disability, the updated RODS will be retested within a larger cohort, with interval testing and further Rasch analysis to ensure reliability and validity.
b) We will perform a longitudinal pilot study into the validity of MRI in POEMS syndrome and other inflammatory neuropathies. We will primarily study markers of axonal damage and fat replacement using Dixon measurements of fat fractions at serial distal-to-proximal sites in the lower limbs. We will also study pre- and post-treatment MRI brain and plexus imaging as pachymeningeal and plexus changes are recognised as part of POEMS syndrome, and investigate with MR neurography if there are any changes in the sciatic nerve on imaging in these diseases. The study aims to determine if known radiological changes correlate with disease severity, and improve with treatment.
REC name
London - Camberwell St Giles Research Ethics Committee
REC reference
21/LO/0518
Date of REC Opinion
9 Aug 2021
REC opinion
Further Information Favourable Opinion