Gaucherite - A Study to Stratify Gaucher Disease
- Conditions
- Gaucher Disease, Type IIIGaucher Disease, Type I
- Interventions
- Other: Stratified response to Enzyme Therapy
- Registration Number
- NCT03240653
- Brief Summary
The purpose of this research is to review data already collected and to collect new data from adults and children in England with Gaucher Disease to determine clinical factors which predict severity and response to therapy of Gaucher disease especially in the areas of bone, cancer and brain conditions.
- Detailed Description
Gaucher disease is part of a rare group of genetic metabolic diseases which are caused by an inherited deficiency of the enzyme glucocerebrosidase. The most common form, Type 1 affects 1 in 40,000 to 60,000 individuals in the general population. In Type 1 symptoms may appear at any time from infancy to old age. The disease is associated with anaemia (a decrease in the amount of red blood cells), fatigue (tiredness), bruising and an increased tendency to bleed. An enlarged spleen and liver with stomach swelling may also occur as well as bone pain, fractures and bone deterioration. Type 1 was formerly considered not to affect the brain or nervous system. Some patients with Type 1 Gaucher disease have no symptoms, while others develop serious symptoms that can be life threatening; latterly Parkinsonism and Dementia with Lewy bodies has been noted to occur with increased frequency in patients with this variant of Gaucher disease compared with healthy control subjects in an age-matched population.
In Gaucher Disease Type 3 the brain and spinal cord are affected. Type 3 is rare and affects fewer than 1 in 100,000 people. The brain and spinal cord symptoms in Type 3 are less severe than in those who have evidence of florid neurologocal disease in infancy years of age. The symptoms of the brain and spinal cord appear in early to late childhood, and patients with Type 3 Gaucher disease live often, but not always, well into adulthood.
Gaucher disease is not gender-specific and its signs and symptoms may appear in affected individuals at any age, with Type 3 being commonly diagnosed in childhood. Although individuals from any ethnic background may develop Gaucher disease, Type 1 Gaucher disease is most common among Jews of Ashkenazi (Eastern European) descent. Among this group, about 1 in 900 people are at risk of Gaucher disease.
There are approximately 280 people in England diagnosed with Gaucher Disease, who receive treatment or management at one of the treating hospitals.
Patients with Gaucher disease have an increased risk of developing myeloma and Parkinson's disease. Myeloma, also known as multiple myeloma, is a type of bone marrow cancer affecting the white blood cells of the immune system which generate antibodies. Approximately 1 in 10 Gaucher patients have a specific blood protein - a monoclonal antibody called a paraprotein, which is found in both malignant and non-malignant conditions, including myeloma.
Parkinson disease is a neurological condition which develops over time as specific brain cells that control movement, die. The failure to produce less of a chemical called dopamine, reduces communication between brain cells involved in the coordination of movement, behaviour, learning and memory.
The investigators will collect information from patients diagnosed with Gaucher disease and any of the conditions mentioned above (for which the patient is already being monitored). Further information required about their clinical status will be obtained from their past and on-going medical records; this will be done as the participants attend hospital as part of their routine care for Gaucher disease. The information we need for the research is no different from the information which is already recorded and will be recorded in their medical notes when they come to the hospital for their routine care, every 6 months.
For the purpose of this study, the investigators will take a few extra blood samples from the participant. These samples will be used to conduct biochemical and cellular analysis solely for the purpose of this research.
The Investigators also request permission from participants to allow access and use for the purpose of the research any archived biological material (blood serum and/or tissue) which may be available from the medical procedures that has been received in the past.
In addition, for the purpose of this research, at each visit, investigators request that the participant also completes questionnaires about physical and social abilities, mental health and quality of life.
All the research-specific procedures (i.e. procedures that the participant would not normally receive during their standard of care hospital visits) can be carried out at either their routine clinic appointments or at another time that the participant would find convenient.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 250
Each patient must meet all of the following criteria to be enrolled in this study:
- Confirmed biochemical diagnosis of Type I, Type II or Type III Gaucher disease
- Written Ethics Committee (EC) approved informed consent obtained from the patient, or patient's parent or legal guardian and patient assent if appropriate
- Male or Female patients, no age limitation
- Willing and able to comply with study schedule and procedures
- Deceased patients for whom the EC determines that patient data can be collected without a new consent from the patient
Patients meeting any of the following criteria will be excluded from the study:
- Unrelated co-morbid condition limiting life expectancy to less than 6 months
- Patient or if applicable, parent or legal guardian is unable to comprehend, sign and date the EC approved informed consent form and patient assent as appropriate
- If determined unsuitable for the study by the investigator
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Patients Type I Stratified response to Enzyme Therapy Stratified response to Enzyme Therapy and Substrate Reduction Therapy- Splenectomy (and interactions) Patients Type III Stratified response to Enzyme Therapy Stratified response to EnzymeTherapy Substrate Reduction Therapy (expected) Splenectomy (and interactions)
- Primary Outcome Measures
Name Time Method Bone avascular necrosis 2029 MRI will allow us to assess new avascular necrosis events (osteonecrosis).
Fragility Fracture 2029 Dual energy absorptive photiometry (DEXA) will allow us to measure the bone mineral density (BMD g/cm2) to enable stratification into treatment strands and predict and prevent future fragility fractures.
Bone Marrow Involvement 2029 MRI will allow us to assess the extent of Bone Marrow involvement and thus response to treatment by using the Bone Marrow Burden Score (BMB). The BMB is a semi quantitative MRI scoring system, using the sagittal T1 and T2 images of the lumbar spine and the coronal T1 and T2 of the femurs.
Cognitive Function 2029 Addenbrooke's Cognitive Examination - ACE-R and National Adult Reading Test are used in combinations to establish attention and orientation, memory, fluency, language and visuospatial orientation
Neurological Physical Assessment 2029 Modified Severity Scoring Tool (MSSt) is used to monitor neurological manifestations of NGD (Type III).
Multiple Myeloma 2029 Characterisation of new biomarkers in the peripheral blood mononuclear cells. (PBMCs), lipid analysis and Metabolomics screen.
Neurological outcome 2029 Presence of saccadic ocular deficits
Disease Severity 2029 Biochemical biomarkers (PARC/CCL18 ng/ml and Chitotriosidase umol/L/h) will be used to perform decease severity and follow-up response to treatment.
- Secondary Outcome Measures
Name Time Method Biobank 2020 Biobank storage of historical and prospective human samples.
EyeSeeCam 2029 Objective quantifiable eye examination measuring eye movement
Quality of life and disease severity measures 2029 PedsQL qual of life for paediatric ages. To assess participant reported quality of life.
Parkinson severity 2029 Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a clinical rating scale for Parkinson's disease (PD)
Trial Locations
- Locations (8)
Salford Royal NHS Foundation Trust
🇬🇧Salford, United Kingdom
Royal Manchester Childrens Hospital
🇬🇧Manchester, United Kingdom
Cambridge University Hospital
🇬🇧Cambridge, United Kingdom
Great Ormond Street Hospital
🇬🇧London, United Kingdom
Birmingham Childrens Hospital
🇬🇧Birmingham, United Kingdom
New Queen Elizabeth Hospital
🇬🇧Birmingham, United Kingdom
Royal Free Hospital
🇬🇧London, United Kingdom
National Hospital for Neurology and Neurosurgery
🇬🇧London, United Kingdom