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Gaucherite - A Study to Stratify Gaucher Disease (Gaucherite)

This study is currently recruiting participants.
Verified August 2017 by Prof Timothy Cox, Cambridge University Hospitals NHS Foundation Trust
Sponsor:
ClinicalTrials.gov Identifier:
NCT03240653
First Posted: August 7, 2017
Last Update Posted: August 14, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Medical Research Council
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
Prof Timothy Cox, Cambridge University Hospitals NHS Foundation Trust
July 12, 2017
August 7, 2017
August 14, 2017
January 1, 2014
September 30, 2017   (Final data collection date for primary outcome measure)
  • Neurological outcome [ Time Frame: 2020 ]
    Presence of saccadic ocular deficits
  • Fragility Fracture [ Time Frame: 2020 ]
    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.
  • Disease Severity [ Time Frame: 2020 ]
    Biochemical biomarkers (PARC/CCL18 ng/ml and Chitotriosidase umol/L/h) will be used to perform decease severity and follow-up response to treatment.
  • Bone Marrow Involvement [ Time Frame: 2020 ]
    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.
  • Bone avascular necrosis [ Time Frame: 2020 ]
    MRI will allow us to assess new avascular necrosis events (osteonecrosis).
  • Cognitive Function [ Time Frame: 2020 ]
    Frontal Assessment Battery (FAB) is used to assess early cognitive impairment in Type III patients and patients with diagnosis of Parkinson disease.
  • Cognitive Function [ Time Frame: 2020 ]
    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 [ Time Frame: 2020 ]
    Modified Severity Scoring Tool (MSSt) is used to monitor neurological manifestations of NGD (Type III).
  • Multiple Myeloma [ Time Frame: 2020 ]
    Characterisation of new biomarkers in the peripheral blood mononuclear cells. (PBMCs), lipid analysis and Metabolomics screen.
  • Neurological outcome [ Time Frame: 2020 ]
    Presence of saccadic ocular deficits
  • Fragility Fracture [ Time Frame: 2020 ]
    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.
  • Disease Severity [ Time Frame: 2020 ]
    Biochemical biomarkers (PARC/CCL18 ng/ml and Chitotriosidase umol/L/h) will be used to perform decease severity and follow-up response to treatment.
  • Bone Marrow Involvement [ Time Frame: 2020 ]
    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.
  • Bone vascular necrosis [ Time Frame: 2020 ]
    MRI will allow us to assess new vascular necrosis events.
  • Cognitive Function [ Time Frame: 2020 ]
    Frontal Assessment Battery (FAB) is used to assess early cognitive impairment in Type III patients and patients with diagnosis of Parkinson disease.
  • Cognitive Function [ Time Frame: 2020 ]
    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 [ Time Frame: 2020 ]
    Modified Severity Scoring Tool (MSSt) is used to monitor neurological manifestations of NGD (Type III).
  • Multiple Myeloma [ Time Frame: 2020 ]
    Characterisation of new biomarkers in the peripheral blood mononuclear cells. (PBMCs), lipid analysis and Metabolomics screen.
Complete list of historical versions of study NCT03240653 on ClinicalTrials.gov Archive Site
  • Quality of life and disease severity measures [ Time Frame: 2020 ]
    SF36; will be used to assess the patient reported quality of life. It is a generic measure of health status, as opposed to one that targets a specific age, disease, or treatment group. It has proven useful for conducting surveys of general and specific populations, comparing the relative burden of diseases, and differentiating the health benefits produced by a wide range of treatments.
  • Quality of life and disease severity measures [ Time Frame: 2020 ]
    EQ5D5L; the dimensions are (mobility, self care, usual activities, pain/discomfort, anxiety/depression). it provides a simple descriptive profile and a single index value for health status that can be used in the clinical and economic evaluation of health. This tool will help facilitating the calculation of quality-adjusted life years (QALYs) that are used to inform economic evaluations of health care interventions.
  • Quality of life and disease severity measures [ Time Frame: 2020 ]
    Hospital anxiety & depression scale (HADs); Assist researchers in detection of emotional disorder in patients under investigation and treatment
  • Quality of life and disease severity measures [ Time Frame: 2020 ]
    PedsQL (multidimensional fatigue scale); Enable researcher to assess if there is a link to level of patient reported fatigue and disease severity
  • Quality of life and disease severity measures [ Time Frame: 2020 ]
    PedsQL qual of life for paediatric ages. To assess participant reported quality of life.
  • Parkinson severity [ Time Frame: 2020 ]
    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)
  • Biobank [ Time Frame: 2020 ]
    Biobank storage of historical and prospective human samples.
Same as current
Not Provided
Not Provided
 
Gaucherite - A Study to Stratify Gaucher Disease
Predictive Measures to Stratify Clinical Outcomes in Children and Adults With Gaucher Disease and Responses to Specific Therapies
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.

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 Types 2 and 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 Type 2 Gaucher disease where children rarely survive beyond two 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 Types 2 and 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.

Observational
Observational Model: Cohort
Time Perspective: Retrospective
Not Provided
Retention:   Samples With DNA
Description:
Urine, Blood (Plasma, Serum, EDTA) Fresh Tissue, Biopsy, Bone Marrow Aspiration & Cerebral Spinal fluid (rarely).
Probability Sample
Eight specialized centres for Gaucher disease in England will recruit approximately 250 patients.
  • Gaucher Disease, Type 1
  • Gaucher Disease, Type 3
Other: Stratified response to Enzyme Therapy
Observational study involving reviewing retrospective and prospective data of participants medical history, pathology, imaging and health questionnaires.
Other Name: Stratified response to Substrate Reduction Therapy
  • Patients Type III
    Stratified response to EnzymeTherapy
    Intervention: Other: Stratified response to Enzyme Therapy
  • Patients Type I
    Stratified response to Enzyme Therapy and Substrate Reduction Therapy
    Intervention: Other: Stratified response to Enzyme Therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
250
September 30, 2020
September 30, 2017   (Final data collection date for primary outcome measure)

Inclusion Criteria:

Each patient must meet all of the following criteria to be enrolled in this study:

  1. Confirmed biochemical diagnosis of Type 1 or Type 3 Gaucher disease
  2. Written Ethics Committee (EC) approved informed consent obtained from the patient, or patient's parent or legal guardian and patient assent if appropriate
  3. Male or Female patients ≥ 5 years of age
  4. Willing and able to comply with study schedule and procedures
  5. Deceased patients for whom the EC determines that patient data can be collected without a new consent from the patient

Exclusion Criteria:

Patients meeting any of the following criteria will be excluded from the study:

  1. Unrelated co-morbid condition limiting life expectancy to less than 6 months
  2. Confirmed Type 2 Gaucher Disease
  3. 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
  4. If determined unsuitable for the study by the investigator
Sexes Eligible for Study: All
5 Years and older   (Child, Adult, Senior)
No
Contact: Kathy K Page, BSc (Hons) 01223767899 kp429@medschl.cam.ac.uk
United Kingdom
 
 
NCT03240653
MR/K015338/1
No
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: Yes
Plan Description: A Data sharing policy will be developed at the end of the study. Researchers will be able to make ethically approved requests to the Data owners for specific data (a charge will be made). What data sets will be available has yet to be decided by the Gaucherite Consortium Group.
Supporting Materials: Study Protocol
Supporting Materials: Informed Consent Form (ICF)
Time Frame: 3 to 4 at completion of study: however given the value of this cohort, efforts will be made to ensure permanence within the National Health Service and the context of NIHR.
Access Criteria: Individual applications made to Data Monitoring Committee and appropriate guarantees of confidentiality and ethical approval.
Prof Timothy Cox, Cambridge University Hospitals NHS Foundation Trust
Cambridge University Hospitals NHS Foundation Trust
  • Medical Research Council
  • National Institute for Health Research, United Kingdom
Principal Investigator: Timothy M Cox University of Cambridge
Cambridge University Hospitals NHS Foundation Trust
August 2017