Magnetic Resonance Spectroscopy in Acid Sphingomyelinase Deficiency
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 34
- 试验地点
- 2
- 主要终点
- Fat fraction in volume percentage measured with MRS-PDFF
研究概览
简要总结
The goal of this study is to assess the ability of MRI techniques to detect early stages of lipid accumulation in the liver of ASMD patients with the chronic visceral subtype compared to healthy subjects.
Participants will undergo an MRI with MR Spectroscopy (MRS) to measure lipid accumulation (steatosis) and MR Elastography (MRE) to measure liver stiffness (fibrosis).
详细描述
Rationale: Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disorder caused by a deficiency of sphingomyelinase resulting in accumulation of the sphingolipid sphingomyelin (SM) in the liver, spleen and lungs. Accumulation of SM in the liver leads to liver fibrosis in a subset of ASMD patients. Enzyme replacement therapy (ERT, olipudase alfa, Sanofi Genzyme) is currently investigated in a phase 2/3 trial and recently received market authorization by the EMA and FDA. As ASMD is a slowly progressive disease, detection of early stages of SM storage in the liver might aid in identifying patients at risk for major complications who would benefit from therapy. Two magnetic resonance (MR) based techniques might be of interest: MR Spectroscopy (MRS) to measure lipid accumulation (steatosis) and MR Elastography (MRE) to measure liver stiffness (fibrosis).
Objective: To assess the ability of MRI techniques to detect early stages of lipid accumulation in the liver of ASMD patients with the chronic visceral subtype compared to healthy subjects.
Study design: Cross-sectional pilot study in which MRS and MRE measurements of ASMD patients will be compared to measurements in healthy subjects. All ASMD patients who participate will undergo an MRI during their yearly assessments. Patients eligible for therapy will also undergo an MRI after one year of treatment.
Study population: All adult patients with ASMD visiting the outpatient clinic for metabolic disorders of the Amsterdam UMC will be invited to participate. Participating ASMD patients will be matched to healthy controls based on age, sex and BMI in a ratio of 1:1.
Main study endpoint: Fat fraction in volume percentage (%) of liver tissue of ASMD patients measured with MRS compared to values of healthy subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •The patient has biochemically proven ASMD (preferably genetically confirmed)
- •The patient is willing and able to provide written informed consent prior to the study-related procedure.
- •The patient is ≥ 18 years of age
- •Healthy controls:
- •The individual is willing and able to provide written informed consent prior to the study-related procedure
- •The individual is ≥ 18 years of age
- •General good health as determined by medical history
排除标准
- •Patients and healthy controls:
- •Inability to adhere to the study protocol
- •Inability to undergo an MRI procedure
结局指标
主要结局
Fat fraction in volume percentage measured with MRS-PDFF
时间窗: 1 year
Fat fraction in volume percentage measured with MRS-PDFF of ASMD patients compared to age-, sex, and BMI-matched healthy subjects.
次要结局
- Correlations between fat fraction and/or liver stiffness and liver parameters(1 year)
- Liver stiffness in kPa measured with MRE(1 year)
- Correlations between fat fraction and/or liver stiffness and general disease parameters(1 year)
研究者
Eline C. B. Eskes
MD
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)