<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03240653</url>
  </required_header>
  <id_info>
    <org_study_id>MR/K015338/1</org_study_id>
    <nct_id>NCT03240653</nct_id>
  </id_info>
  <brief_title>Gaucherite - A Study to Stratify Gaucher Disease</brief_title>
  <acronym>Gaucherite</acronym>
  <official_title>Predictive Measures to Stratify Clinical Outcomes in Children and Adults With Gaucher Disease and Responses to Specific Therapies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cambridge University Hospitals NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Medical Research Council</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute for Health Research, United Kingdom</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Cambridge University Hospitals NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research is to review data already collected and to collect new data from&#xD;
      adults and children in England with Gaucher Disease to determine clinical factors which&#xD;
      predict severity and response to therapy of Gaucher disease especially in the areas of bone,&#xD;
      cancer and brain conditions.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Gaucher disease is part of a rare group of genetic metabolic diseases which are caused by an&#xD;
      inherited deficiency of the enzyme glucocerebrosidase. The most common form, Type 1 affects 1&#xD;
      in 40,000 to 60,000 individuals in the general population. In Type 1 symptoms may appear at&#xD;
      any time from infancy to old age. The disease is associated with anaemia (a decrease in the&#xD;
      amount of red blood cells), fatigue (tiredness), bruising and an increased tendency to bleed.&#xD;
      An enlarged spleen and liver with stomach swelling may also occur as well as bone pain,&#xD;
      fractures and bone deterioration. Type 1 was formerly considered not to affect the brain or&#xD;
      nervous system. Some patients with Type 1 Gaucher disease have no symptoms, while others&#xD;
      develop serious symptoms that can be life threatening; latterly Parkinsonism and Dementia&#xD;
      with Lewy bodies has been noted to occur with increased frequency in patients with this&#xD;
      variant of Gaucher disease compared with healthy control subjects in an age-matched&#xD;
      population.&#xD;
&#xD;
      In Gaucher Disease Type 3 the brain and spinal cord are affected. Type 3 is rare and affects&#xD;
      fewer than 1 in 100,000 people. The brain and spinal cord symptoms in Type 3 are less severe&#xD;
      than in those who have evidence of florid neurologocal disease in infancy years of age. The&#xD;
      symptoms of the brain and spinal cord appear in early to late childhood, and patients with&#xD;
      Type 3 Gaucher disease live often, but not always, well into adulthood.&#xD;
&#xD;
      Gaucher disease is not gender-specific and its signs and symptoms may appear in affected&#xD;
      individuals at any age, with Type 3 being commonly diagnosed in childhood. Although&#xD;
      individuals from any ethnic background may develop Gaucher disease, Type 1 Gaucher disease is&#xD;
      most common among Jews of Ashkenazi (Eastern European) descent. Among this group, about 1 in&#xD;
      900 people are at risk of Gaucher disease.&#xD;
&#xD;
      There are approximately 280 people in England diagnosed with Gaucher Disease, who receive&#xD;
      treatment or management at one of the treating hospitals.&#xD;
&#xD;
      Patients with Gaucher disease have an increased risk of developing myeloma and Parkinson's&#xD;
      disease. Myeloma, also known as multiple myeloma, is a type of bone marrow cancer affecting&#xD;
      the white blood cells of the immune system which generate antibodies. Approximately 1 in 10&#xD;
      Gaucher patients have a specific blood protein - a monoclonal antibody called a paraprotein,&#xD;
      which is found in both malignant and non-malignant conditions, including myeloma.&#xD;
&#xD;
      Parkinson disease is a neurological condition which develops over time as specific brain&#xD;
      cells that control movement, die. The failure to produce less of a chemical called dopamine,&#xD;
      reduces communication between brain cells involved in the coordination of movement,&#xD;
      behaviour, learning and memory.&#xD;
&#xD;
      The investigators will collect information from patients diagnosed with Gaucher disease and&#xD;
      any of the conditions mentioned above (for which the patient is already being monitored).&#xD;
      Further information required about their clinical status will be obtained from their past and&#xD;
      on-going medical records; this will be done as the participants attend hospital as part of&#xD;
      their routine care for Gaucher disease. The information we need for the research is no&#xD;
      different from the information which is already recorded and will be recorded in their&#xD;
      medical notes when they come to the hospital for their routine care, every 6 months.&#xD;
&#xD;
      For the purpose of this study, the investigators will take a few extra blood samples from the&#xD;
      participant. These samples will be used to conduct biochemical and cellular analysis solely&#xD;
      for the purpose of this research.&#xD;
&#xD;
      The Investigators also request permission from participants to allow access and use for the&#xD;
      purpose of the research any archived biological material (blood serum and/or tissue) which&#xD;
      may be available from the medical procedures that has been received in the past.&#xD;
&#xD;
      In addition, for the purpose of this research, at each visit, investigators request that the&#xD;
      participant also completes questionnaires about physical and social abilities, mental health&#xD;
      and quality of life.&#xD;
&#xD;
      All the research-specific procedures (i.e. procedures that the participant would not normally&#xD;
      receive during their standard of care hospital visits) can be carried out at either their&#xD;
      routine clinic appointments or at another time that the participant would find convenient.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 1, 2014</start_date>
  <completion_date type="Anticipated">December 31, 2028</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2028</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Neurological outcome</measure>
    <time_frame>2029</time_frame>
    <description>Presence of saccadic ocular deficits</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Fragility Fracture</measure>
    <time_frame>2029</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Disease Severity</measure>
    <time_frame>2029</time_frame>
    <description>Biochemical biomarkers (PARC/CCL18 ng/ml and Chitotriosidase umol/L/h) will be used to perform decease severity and follow-up response to treatment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Bone Marrow Involvement</measure>
    <time_frame>2029</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Bone avascular necrosis</measure>
    <time_frame>2029</time_frame>
    <description>MRI will allow us to assess new avascular necrosis events (osteonecrosis).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cognitive Function</measure>
    <time_frame>2019</time_frame>
    <description>Frontal Assessment Battery (FAB) is used to assess early cognitive impairment in Type III patients and patients with diagnosis of Parkinson disease.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cognitive Function</measure>
    <time_frame>2029</time_frame>
    <description>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</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Neurological Physical Assessment</measure>
    <time_frame>2029</time_frame>
    <description>Modified Severity Scoring Tool (MSSt) is used to monitor neurological manifestations of NGD (Type III).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Multiple Myeloma</measure>
    <time_frame>2029</time_frame>
    <description>Characterisation of new biomarkers in the peripheral blood mononuclear cells. (PBMCs), lipid analysis and Metabolomics screen.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Quality of life and disease severity measures</measure>
    <time_frame>2029</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life and disease severity measures</measure>
    <time_frame>2029</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life and disease severity measures</measure>
    <time_frame>2029</time_frame>
    <description>Hospital anxiety &amp; depression scale (HADs); Assist researchers in detection of emotional disorder in patients under investigation and treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life and disease severity measures</measure>
    <time_frame>2029</time_frame>
    <description>PedsQL (multidimensional fatigue scale); Enable researcher to assess if there is a link to level of patient reported fatigue and disease severity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life and disease severity measures</measure>
    <time_frame>2029</time_frame>
    <description>PedsQL qual of life for paediatric ages. To assess participant reported quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Parkinson severity</measure>
    <time_frame>2029</time_frame>
    <description>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)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biobank</measure>
    <time_frame>2020</time_frame>
    <description>Biobank storage of historical and prospective human samples.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EyeSeeCam</measure>
    <time_frame>2029</time_frame>
    <description>Objective quantifiable eye examination measuring eye movement</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">250</enrollment>
  <condition>Gaucher Disease, Type I</condition>
  <condition>Gaucher Disease, Type III</condition>
  <arm_group>
    <arm_group_label>Patients Type III</arm_group_label>
    <description>Stratified response to EnzymeTherapy Substrate Reduction Therapy (expected) Splenectomy (and interactions)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients Type I</arm_group_label>
    <description>Stratified response to Enzyme Therapy and Substrate Reduction Therapy- Splenectomy (and interactions)</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Stratified response to Enzyme Therapy</intervention_name>
    <description>Observational study involves review of retrospective and prospective data of participants' medical history, pathology, imaging and health questionnaires.</description>
    <arm_group_label>Patients Type I</arm_group_label>
    <arm_group_label>Patients Type III</arm_group_label>
    <other_name>Stratified response to Substrate Reduction Therapy</other_name>
    <other_name>Splenectormy</other_name>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Urine, Blood (Plasma, Serum, EDTA) Fresh Tissue, Biopsy, Bone Marrow Aspiration &amp;&#xD;
      Cerebro-spinal fluid (rarely).&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Seven (previously eight) specialized centres for Gaucher disease in England will recruit&#xD;
        approximately 280 patients.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Each patient must meet all of the following criteria to be enrolled in this study:&#xD;
&#xD;
          1. Confirmed biochemical diagnosis of Type I, Type II or Type III Gaucher disease&#xD;
&#xD;
          2. Written Ethics Committee (EC) approved informed consent obtained from the patient, or&#xD;
             patient's parent or legal guardian and patient assent if appropriate&#xD;
&#xD;
          3. Male or Female patients, no age limitation&#xD;
&#xD;
          4. Willing and able to comply with study schedule and procedures&#xD;
&#xD;
          5. Deceased patients for whom the EC determines that patient data can be collected&#xD;
             without a new consent from the patient&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients meeting any of the following criteria will be excluded from the study:&#xD;
&#xD;
          1. Unrelated co-morbid condition limiting life expectancy to less than 6 months&#xD;
&#xD;
          2. Patient or if applicable, parent or legal guardian is unable to comprehend, sign and&#xD;
             date the EC approved informed consent form and patient assent as appropriate&#xD;
&#xD;
          3. If determined unsuitable for the study by the investigator&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Timothy M Cox, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Cambridge</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Elizabeth M MORRIS, RN</last_name>
    <phone>+441223274634</phone>
    <email>liz.morris@addenbrookes.nhs.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Chong Y TAN, MB PhD</last_name>
    <phone>+441223274634</phone>
    <email>chongyew.tan@addenbrookes.nhs.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Birmingham Childrens Hospital</name>
      <address>
        <city>Birmingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>New Queen Elizabeth Hospital</name>
      <address>
        <city>Birmingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kathy Page, BSc(Hons)</last_name>
      <phone>01223 767899</phone>
      <email>kp429@medschl.cam.ac.uk</email>
    </contact>
    <investigator>
      <last_name>Tarekegn Hiwot</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Cambridge University Hospital</name>
      <address>
        <city>Cambridge</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Liz M Morris, RN</last_name>
      <phone>+441223-274634</phone>
      <email>Liz.morris@addenbrookes.nhs.uk</email>
    </contact>
    <investigator>
      <last_name>Patrick Deegan, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Great Ormond Street Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kathy Page, BSc (Hons)</last_name>
      <phone>01223767899</phone>
      <email>kp429@medschl.cam.ac.uk</email>
    </contact>
    <investigator>
      <last_name>Anupam Chakrapani</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>National Hospital for Neurology and Neurosurgery</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kathy Page, BSc(Hons)</last_name>
      <phone>01223 767899</phone>
      <email>kp429@medschl.cam.ac.uk</email>
    </contact>
    <investigator>
      <last_name>Robin Lachmann</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Royal Free Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kathy Page, BSc (Hons)</last_name>
      <phone>01223767899</phone>
      <email>kp429@medschl.cam.ac.uk</email>
    </contact>
    <investigator>
      <last_name>Derralynn Hughes</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Royal Manchester Childrens Hospital</name>
      <address>
        <city>Manchester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kathy Page, BSc (Hons)</last_name>
      <phone>01223 767899</phone>
      <email>kp429@medschl.cam.ac.uk</email>
    </contact>
    <investigator>
      <last_name>Simon Jones</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Salford Royal NHS Foundation Trust</name>
      <address>
        <city>Salford</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kathy Page, BSc(Hons)</last_name>
      <phone>01223 767899</phone>
      <email>kp429@medschl.cam.ac.uk</email>
    </contact>
    <investigator>
      <last_name>Reena Sharma</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>D'Amore S, Page K, Donald A, Taiyari K, Tom B, Deegan P, Tan CY, Poole K, Jones SA, Mehta A, Hughes D, Sharma R, Lachmann RH, Chakrapani A, Geberhiwot T, Santra S, Banka S, Cox TM; MRC GAUCHERITE Consortium. In-depth phenotyping for clinical stratification of Gaucher disease. Orphanet J Rare Dis. 2021 Oct 14;16(1):431. doi: 10.1186/s13023-021-02034-6.</citation>
    <PMID>34649574</PMID>
  </reference>
  <reference>
    <citation>Donald A, Bjorkvall CK, Vellodi A; GAUCHERITE Consortium; Cox TM, Hughes D, Jones SA, Wynn R, Machaczka M. Thirty-year clinical outcomes after haematopoietic stem cell transplantation in neuronopathic Gaucher disease. Orphanet J Rare Dis. 2022 Jun 18;17(1):234. doi: 10.1186/s13023-022-02378-7.</citation>
    <PMID>35717194</PMID>
  </reference>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>July 12, 2017</study_first_submitted>
  <study_first_submitted_qc>August 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2017</study_first_posted>
  <last_update_submitted>May 5, 2023</last_update_submitted>
  <last_update_submitted_qc>May 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cambridge University Hospitals NHS Foundation Trust</investigator_affiliation>
    <investigator_full_name>Timothy Cox MD</investigator_full_name>
    <investigator_title>Professor of Medicine Emeritus, Director of Research, Honorary Consultant</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gaucher Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_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.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>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.</ipd_time_frame>
    <ipd_access_criteria>Individual applications made to Data Monitoring Committee and appropriate guarantees of confidentiality and ethical approval.</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03240653
org study id: MR/K015338/1
nct id: NCT03240653
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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 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.
observational model: Cohort
time perspective: Retrospective
measure: Neurological outcome
time frame: 2029
description: Presence of saccadic ocular deficits
measure: Fragility Fracture
time frame: 2029
description: 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.
measure: Disease Severity
time frame: 2029
description: Biochemical biomarkers (PARC/CCL18 ng/ml and Chitotriosidase umol/L/h) will be used to perform decease severity and follow-up response to treatment.
measure: Bone Marrow Involvement
time frame: 2029
description: 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.
measure: Bone avascular necrosis
time frame: 2029
description: MRI will allow us to assess new avascular necrosis events (osteonecrosis).
measure: Cognitive Function
time frame: 2019
description: Frontal Assessment Battery (FAB) is used to assess early cognitive impairment in Type III patients and patients with diagnosis of Parkinson disease.
measure: Cognitive Function
time frame: 2029
description: 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
measure: Neurological Physical Assessment
time frame: 2029
description: Modified Severity Scoring Tool (MSSt) is used to monitor neurological manifestations of NGD (Type III).
measure: Multiple Myeloma
time frame: 2029
description: Characterisation of new biomarkers in the peripheral blood mononuclear cells. (PBMCs), lipid analysis and Metabolomics screen.
measure: Quality of life and disease severity measures
time frame: 2029
description: 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.
measure: Quality of life and disease severity measures
time frame: 2029
description: 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.
measure: Quality of life and disease severity measures
time frame: 2029
description: Hospital anxiety & depression scale (HADs); Assist researchers in detection of emotional disorder in patients under investigation and treatment
measure: Quality of life and disease severity measures
time frame: 2029
description: PedsQL (multidimensional fatigue scale); Enable researcher to assess if there is a link to level of patient reported fatigue and disease severity
measure: Quality of life and disease severity measures
time frame: 2029
description: PedsQL qual of life for paediatric ages. To assess participant reported quality of life.
measure: Parkinson severity
time frame: 2029
description: 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)
measure: Biobank
time frame: 2020
description: Biobank storage of historical and prospective human samples.
measure: EyeSeeCam
time frame: 2029
description: Objective quantifiable eye examination measuring eye movement
arm group label: Patients Type III
description: Stratified response to EnzymeTherapy Substrate Reduction Therapy (expected) Splenectomy (and interactions)
arm group label: Patients Type I
description: Stratified response to Enzyme Therapy and Substrate Reduction Therapy- Splenectomy (and interactions)
intervention type: Other
intervention name: Stratified response to Enzyme Therapy
description: Observational study involves review of retrospective and prospective data of participants' medical history, pathology, imaging and health questionnaires.
arm group label: Patients Type I
arm group label: Patients Type III
other name: Stratified response to Substrate Reduction Therapy
other name: Splenectormy
Urine, Blood (Plasma, Serum, EDTA) Fresh Tissue, Biopsy, Bone Marrow Aspiration &
      Cerebro-spinal fluid (rarely).
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Timothy M Cox, MD
role: Principal Investigator
affiliation: University of Cambridge
last name: Elizabeth M MORRIS, RN
phone: +441223274634
email: liz.morris@addenbrookes.nhs.uk
last name: Chong Y TAN, MB PhD
phone: +441223274634
email: chongyew.tan@addenbrookes.nhs.uk
facility: 
status: Terminated
facility: 
status: Recruiting
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country: United Kingdom
citation: D'Amore S, Page K, Donald A, Taiyari K, Tom B, Deegan P, Tan CY, Poole K, Jones SA, Mehta A, Hughes D, Sharma R, Lachmann RH, Chakrapani A, Geberhiwot T, Santra S, Banka S, Cox TM; MRC GAUCHERITE Consortium. In-depth phenotyping for clinical stratification of Gaucher disease. Orphanet J Rare Dis. 2021 Oct 14;16(1):431. doi: 10.1186/s13023-021-02034-6.
PMID: 34649574
citation: Donald A, Bjorkvall CK, Vellodi A; GAUCHERITE Consortium; Cox TM, Hughes D, Jones SA, Wynn R, Machaczka M. Thirty-year clinical outcomes after haematopoietic stem cell transplantation in neuronopathic Gaucher disease. Orphanet J Rare Dis. 2022 Jun 18;17(1):234. doi: 10.1186/s13023-022-02378-7.
PMID: 35717194
responsible party type: Principal Investigator
investigator affiliation: Cambridge University Hospitals NHS Foundation Trust
investigator full name: Timothy Cox MD
investigator title: Professor of Medicine Emeritus, Director of Research, Honorary Consultant
mesh term: Gaucher Disease
sharing ipd: Yes
ipd 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.
ipd info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd time frame: 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.
ipd access criteria: Individual applications made to Data Monitoring Committee and appropriate guarantees of confidentiality and ethical approval.