Clinical trial NCT03240653: Gaucherite - A Study to Stratify Gaucher Disease
Official title: Predictive Measures to Stratify Clinical Outcomes in Children and Adults With Gaucher Disease and Responses to Specific Therapies
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Gaucher Disease, Type I
Gaucher Disease, Type III
Lead sponsor: Cambridge University Hospitals NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Medical Research Council
name: National Institute for Health Research, United Kingdom
First posted: 2017-08-07
Enrollment: 250
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Seven (previously eight) specialized centres for Gaucher disease in England will recruit approximately 280 patients.

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.

Eligibility criteria: Inclusion Criteria:

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

1. Confirmed biochemical diagnosis of Type I, Type II or Type III 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, no age limitation
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. 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
3. If determined unsuitable for the study by the investigator

Primary outcomes:
measure: Neurological outcome
timeFrame: 2029
measure: Fragility Fracture
timeFrame: 2029
measure: Disease Severity
timeFrame: 2029
measure: Bone Marrow Involvement
timeFrame: 2029
measure: Bone avascular necrosis
timeFrame: 2029
measure: Cognitive Function
timeFrame: 2019
measure: Cognitive Function
timeFrame: 2029
measure: Neurological Physical Assessment
timeFrame: 2029
measure: Multiple Myeloma
timeFrame: 2029
Secondary outcomes:
measure: Quality of life and disease severity measures
timeFrame: 2029
measure: Quality of life and disease severity measures
timeFrame: 2029
measure: Quality of life and disease severity measures
timeFrame: 2029
measure: Quality of life and disease severity measures
timeFrame: 2029
measure: Quality of life and disease severity measures
timeFrame: 2029
measure: Parkinson severity
timeFrame: 2029
measure: Biobank
timeFrame: 2020
measure: EyeSeeCam
timeFrame: 2029
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: Birmingham Childrens Hospital
city: Birmingham
country: United Kingdom
facility: New Queen Elizabeth Hospital
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
city: London
country: United Kingdom
facility: National Hospital for Neurology and Neurosurgery
city: London
country: United Kingdom
facility: Royal Free Hospital
city: Manchester
country: United Kingdom
facility: Royal Manchester Childrens Hospital
city: Salford
country: United Kingdom
facility: Salford Royal NHS Foundation Trust
Study officials:
affiliation: University of Cambridge
name: Timothy M Cox, MD
role: PRINCIPAL_INVESTIGATOR
References:
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: 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: 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.
citation: 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.
citation: 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.