Gaucherite - A study to classify Gaucher disease
Research type
Research Study
Full title
Predictive measures to stratify clinical outcomes in children and adults with Gaucher disease and responses to specific therapies
IRAS ID
146801
Contact name
Timothy M. Cox
Contact email
Sponsor organisation
Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge
Clinicaltrials.gov Identifier
A093165, Cambridge University R&D
Duration of Study in the UK
5 years, 0 months, 2 days
Research summary
Gaucher disease, the most common inborn lysosomal disorder, is due to deficiency of ß-glucosylceramidase encoded by the GBA1 gene. Life-quality is impaired, survival is reduced and crippling skeletal disease, marrow failure, visceromegaly, cancers, disabling neurological effects, including late-onset Parkinsonism, supervene. Diverse manifestations, discrepant between siblings, twins and even monozygotic twin sets, show that clinical disease and treatment responses are not determined by GBA1 genotype alone: in-depth clinical phenotyping is critical for robust stratification and for therapeutic advance.
The overarching aim of the research is to improve treatment of Gaucher disease using clinical stratification and severity categories based on therapeutic responses.
National specialized centres for Gaucher disease will recruit =85% of UK patients (~250). Beyond limited clinical nomenclature (types 1-3), study cohorts defined by high-resolution stratification of clinical phenotypes will use validated disease severity and life-quality scores to annotate therapeutic responses; we will explore the predictive value of the activated inflammasome and bioactive lipids, as well as established plasma enzymatic and chemokine biomarkers. Partner biostatisticians (MRC external staff) will conduct time-to-event and regression modelling analyses to develop treatment cohorts based on dosing studies and stage of intervention; serial biological samples will be stored and data entered on the custom-designed national Gaucher register at all centres.
We will focus on two research strands (neurological and osseous disease) in adults and children, and seek determinants of outcome. The neurological research strand aims to identify factors that predispose to progressive (e.g. myoclonic) epilepsy (often fatal) and in adults seek added risk factors for Parkinsonism - clinical characteristics, family history and genetic variation (including GBA1). The osseous disease research strand will add paediatric data and expand the pre-existing joint database of 100 adults with skeletal growth, mobility and pain scores.
Stratification will lead to a dynamic platform for advancing therapy and further understanding of disease causation.REC name
East of England - Essex Research Ethics Committee
REC reference
14/EE/1168
Date of REC Opinion
19 Dec 2014
REC opinion
Further Information Favourable Opinion