Gaucherite - A Study to Stratify Gaucher Disease

NCT03240653 | Recruiting

• 1 other identifier: MR/K015338/1
• Study Type: observational
• Target: 250
• Locations: 1 country
• Sites: 8

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.

Conditions

Gaucher Disease, Type I; Gaucher Disease, Type III

Outcome Measures

Primary Outcomes (9)

• Neurological outcome

  Presence of saccadic ocular deficits

  2029

• Fragility Fracture

  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.

  2029

• Disease Severity

  Biochemical biomarkers (PARC/CCL18 ng/ml and Chitotriosidase umol/L/h) will be used to perform decease severity and follow-up response to treatment.

  2029

• Bone Marrow Involvement

  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.

  2029

• Bone avascular necrosis

  MRI will allow us to assess new avascular necrosis events (osteonecrosis).

  2029

• Cognitive Function

  Frontal Assessment Battery (FAB) is used to assess early cognitive impairment in Type III patients and patients with diagnosis of Parkinson disease.

  2019

• Cognitive Function

  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

  2029

• Neurological Physical Assessment

  Modified Severity Scoring Tool (MSSt) is used to monitor neurological manifestations of NGD (Type III).

  2029

• Multiple Myeloma

  Characterisation of new biomarkers in the peripheral blood mononuclear cells. (PBMCs), lipid analysis and Metabolomics screen.

  2029

Secondary Outcomes (8)

• Quality of life and disease severity measures

  2029

• Quality of life and disease severity measures

  2029

• Quality of life and disease severity measures

  2029

• Quality of life and disease severity measures

  2029

• Quality of life and disease severity measures

  2029

Study Arms (2)

Patients Type III

Stratified response to EnzymeTherapy Substrate Reduction Therapy (expected) Splenectomy (and interactions)

Other: Stratified response to Enzyme Therapy

Patients Type I

Stratified response to Enzyme Therapy and Substrate Reduction Therapy- Splenectomy (and interactions)

Other: Stratified response to Enzyme Therapy

Interventions

Stratified response to Enzyme Therapy OTHER

Observational study involves review of retrospective and prospective data of participants' medical history, pathology, imaging and health questionnaires.

Also known as: Stratified response to Substrate Reduction Therapy, Splenectormy

Patients Type I; Patients Type III

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Seven (previously eight) specialized centres for Gaucher disease in England will recruit approximately 280 patients.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cambridge University Hospitals NHS Foundation Trust: lead
• Medical Research Council: collaborator
• National Institute for Health Research, United Kingdom: collaborator

Study Sites (8)

Birmingham Childrens Hospital

Birmingham, United Kingdom

TERMINATED

New Queen Elizabeth Hospital

Birmingham, United Kingdom

RECRUITING

Cambridge University Hospital

Cambridge, United Kingdom

RECRUITING

Great Ormond Street Hospital

London, United Kingdom

RECRUITING

National Hospital for Neurology and Neurosurgery

London, United Kingdom

RECRUITING

Royal Free Hospital

London, United Kingdom

RECRUITING

Royal Manchester Childrens Hospital

Manchester, United Kingdom

RECRUITING

Salford Royal NHS Foundation Trust

Salford, United Kingdom

RECRUITING

Related Publications (7)

• 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 BACKGROUND

• 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 BACKGROUND

• Donald A, Tan CY, Chakrapani A, Hughes DA, Sharma R, Cole D, Bardins S, Gorges M, Jones SA, Schneider E. Eye movement biomarkers allow for the definition of phenotypes in Gaucher Disease. Orphanet J Rare Dis. 2020 Dec 17;15(1):349. doi: 10.1186/s13023-020-01637-9.

  PMID: 33334373 BACKGROUND

• Adusumilli G, Kaggie JD, D'Amore S, Cox TM, Deegan P, MacKay JW, McDonald S; GAUCHERITE Consortium. Improving the quantitative classification of Erlenmeyer flask deformities. Skeletal Radiol. 2021 Feb;50(2):361-369. doi: 10.1007/s00256-020-03561-2. Epub 2020 Jul 30.

  PMID: 32734372 BACKGROUND

• Yu B, Whitmarsh T, Riede P, McDonald S, Kaggie JD, Cox TM, Poole KES, Deegan P; MRC Gaucherite consortium. Deep learning-based quantification of osteonecrosis using magnetic resonance images in Gaucher disease. Bone. 2024 Sep;186:117142. doi: 10.1016/j.bone.2024.117142. Epub 2024 Jun 2.

  PMID: 38834102 BACKGROUND

• Donald A, Jones SA, Hughes DA, Church HJ; GAUCHERITE Consortium; Cox TM. Gaucher disease type 3: Classification of the chronic neuronopathic variant informed by genotype in a phenotypically diverse cohort. Genet Med. 2025 Sep;27(9):101502. doi: 10.1016/j.gim.2025.101502. Epub 2025 Jun 18.

  PMID: 40542647 DERIVED

• D'Amore S, Sano H, Chappell DDG, Chiarugi D, Baker O, Page K, Ramaswami U, Johannesdottir F, Cox TM, Deegan P, Poole KE; MRC Gaucherite Consortium; MRC Gaucherite Consortium Collaborators. Radiographic Cortical Thickness Index Predicts Fragility Fracture in Gaucher Disease. Radiology. 2023 Apr;307(1):e212779. doi: 10.1148/radiol.212779. Epub 2022 Dec 20.

  PMID: 36537898 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Urine, Blood (Plasma, Serum, EDTA) Fresh Tissue, Biopsy, Bone Marrow Aspiration \& Cerebro-spinal fluid (rarely).

MeSH Terms

Conditions

Gaucher Disease

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Officials

• Timothy M Cox, MD

  University of Cambridge

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elizabeth M MORRIS, RN

CONTACT

+441223274634; liz.morris@addenbrookes.nhs.uk

Chong Y TAN, MB PhD

CONTACT

+441223274634; chongyew.tan@addenbrookes.nhs.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine Emeritus, Director of Research, Honorary Consultant

Study Record Dates

• First Submitted: July 12, 2017
• First Posted: August 7, 2017
• Study Start: January 1, 2014
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: August 6, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• 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.
• Access Criteria: Individual applications made to Data Monitoring Committee and appropriate guarantees of confidentiality and ethical approval.

Locations

GB (8)