Natural History of Morquio B and Late-Onset GM1 Gangliosidosis
试验速览
- 阶段
- 不适用
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- CNS involvement
研究概览
简要总结
Mucopolysaccharidosis type IVB (Morquio-B disease, MBD) is an autosomal-recessive lysosomal disease caused by mutations in a gene called GLB1. Clinically, Morquio B presents with progressive skeletal deformities involving mostly long bones and spine. While the information on GLB1 mutations associated with MBD is limited, there is a significant overlap in clinical presentation between Morquio B and late-onset GM1 gangliosidosis with both conditions being caused by mutations in the same GLB1 gene. In this study, the investigators plan to collect retrospective data from patients' medical charts, as well as, information from the prospective follow up clinic visits. There will be two study visits with the interval of one year. The study procedures will include a detailed physical exam, bone scans, heart and lung function, physical endurance tests, hearing test, laboratory tests and quality of life surveys.
The purpose of this study is to collect data on the natural history of Morquio B and to create a biobank of laboratory samples (blood, urine and skin cells) for future research. This information will improve the understanding of the natural progression of Morquio B disease.
详细描述
The primary objective of this study is to establish the natural history of Morquio B (Mucopolysaccharidosis type IVB, MBD) disease through the collection and analysis of retrospective and prospective data on patients diagnosed with Morquio B. Because of significant overlap in clinical presentation, patients with late-onset GM1 will also be included.
Upon consent, data from clinical, laboratory, functional and quality of life studies, and data from review of medical records will be collected and analyzed descriptively. In addition, the samples of blood, urine and fibroblasts will be collected and stored at BC Children Hospital Research Institute Biobank for future research. The prospective follow up will include two clinic visits, one year apart. The following data will be collected during the prospective observational part of the study (as per study protocol) and retrospective part (whether such data are available from the medical chart):
- Medical history: Morquio B / Late-onset GM1 gangliosidosis diagnosis, presentation, treatments and symptom progression
- Physical exam, including neurological and ophthalmological assessments
- Standard Grip Strength Evaluation
- Range of motion
- Six-minute walk test (6MWT)
- 3-Minute Stair Climb Test
- Gait and Motion assessment
- Pulmonary function testing
- Hearing test
- Echocardiography
- EKG
- X-ray (lumbar spine, upper & lower limbs, hip)
- DXA scan
- Brain MRI
- Laboratory tests (GAGs assay and pro-inflammatory cytokine panel)
- Blood, urine and fibroblast samples for biobanking
- Genetic test (if not done per standard of care)
Additional assessments and evaluations:
• Patient-reported outcomes: quality of life SF-36, MPS HAQ and the interview on personally meaningful outcomes
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of beta-galactosidase deficiency via demonstration of deficient enzyme activity and/or demonstration of homozygous/compound heterozygous pathogenic GLB1 variants;
- •Patients diagnosed with beta-galactosidase deficiency and who present with "MPSIVB skeletal phenotype" with or without primary CNS involvement;
- •Patient / parent or legal guardian is able to read, understand, and sign the informed consent.
排除标准
- •Previous Hematopoietic Stem Cell Transplant procedure (HSCT);
- •Concurrent disease or condition that would interfere with participation in the study and/or travel to the site (for the prospective follow up);
- •Previous or current casual treatments that might affect the natural course of the disease;
- •Patient's (guardian's) not understanding and/or not agreeing to the informed consent form;
- •GM1-gangliosidosis patients who present without "MPSIVB skeletal phenotype"
结局指标
主要结局
CNS involvement
时间窗: Through study completion, an average of 1 year
Neurological assessments, Brain MRI
Physical Development
时间窗: Through study completion, an average of 1 year
Growth rate
Range of Motion Scale
时间窗: Through study completion, an average of 1 year
Assessments: shoulder, elbow, wrist, hip, knee, ankle
Physical Endurance
时间窗: 1 year
Standard Grip Strength evaluation
Skeletal involvement
时间窗: Through study completion, an average of 1 year
X-ray studies, pQCT (where available), DXA of lateral distal femur, x-ray and/or MRI of cervical spine to assess spinal stenosis and spinal cord compression; X-ray of cervical spine to assess odontoid hypoplasia and atlantoaxial instability
Surrogate biomarkers
时间窗: Baseline and 1 year
Comprehensive pro-inflammatory cytokine panel with markers of bone turnover
Personally Meaningful Outcomes
时间窗: Baseline and 1 year
PMO Questionnaire
Health-related Quality of Life (HRQoL)
时间窗: Baseline and 1 year
SF-36
Health-related Quality of Life (HRQoL) and Activities of Daily living (ADLs)
时间窗: Baseline and 1 year
MPS-HAQ
次要结局
未报告次要终点
研究者
Sylvia Stockler
MD, PhD, MBA, FRCPC
University of British Columbia