Innovative Therapeutic Strategy Targeting Neurons with Cholesterol in Huntington Disease: from Preclinical Studies to Clinical Trial Readiness
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- plasmatic 24OHC levels
研究概览
简要总结
A 2-year clinical longitudinal study to measure plasma concentrations of 24S-hydroxycholesterol, a brain-derived cholesterol catabolite, in subjects with Huntington disease, from the presymptomatic to the symptomatic stages.
详细描述
In cross-sectional studies, the plasma level of brain-derived 24S-hydroxycholesterol (24OHC) has been found to be significantly diminished in HD patients from the first stages of the disease. Furthermore, in HD gene-positive pre-symptomatic (pre-HD) the plasma levels can predict the development of motor signs of disease in subjects closer to onset, better than in subjects far from onset. These data suggest that circulating 24OHC might be a candidate biomarker for phenotypic conversion and for disease progression in different stages of the disease.
Detailed neurological, cognitive and imaging data and blood samples will be collected at baseline, and after two years to investigate the rate of changes along the longitudinal study. Isotope dilution mass spectrometry (assay performed at Istituto di Ricerche Farmacologiche Mario Negri IRCCS) will be used to measure the plasma levels of brain-derived 24OHC and other sterols reflecting peripheral cholesterol synthesis. The investigators expect to establish whether changes in plasma 24OHC mark disease progression and, eventually, phenoconversion from pre-symptomatic to symptomatic stages in combination with clinical, cognitive and imaging parameters.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Symptomatic HD subjects
- •Age ≥ 18 years
- •Known family history of HD and genetically confirmed disease by direct DNA test (CAG expansion > 35 repeats)
- •Clinical diagnostic motor features of HD, defined as score> 5 at the motor Unified Huntington Disease Rating Scale (mUHDRS)
- •Stage I or II or III HD, defined as UHDRS Total Functional Capacity (TFC) scores between 3 and 13 inclusive (Marder, 2000)
- •Presymptomatic HD subjects
- •Age ≥ 18 years
- •Known family history of HD and genetically confirmed mutation by direct DNA test (CAG expansion > 35 repeats)
- •Absence of clinical motor features of HD, defined as mUHDRS rating scale ≤ 5
- •Healthy Subjects
- •Age ≥ 18 years
- •Absence of known family history of HD or genetically confirmed negative DNA test for HD (CAG expansion ≤ 35 repeats)
- •Absence of clinical motor features of HD, defined as mUHDRS rating scale ≤ 5
排除标准
- •Participation in clinical pharmacological trials
- •Inability to undergo and tolerate MRI scans (e.g. claustrophobia, severe chorea, MRI-incompatible intrauterine devices, metal implants, ect)
- •Inability or unwillingness to undertake any of the study procedures
结局指标
主要结局
plasmatic 24OHC levels
时间窗: at baseline and after 2-years follow up visit
Changes in plasmatic 24OHC levels measured
次要结局
- Changes in the score of the Unified Huntington Disease Rating Scale (UHDRS)(after 2-years follow up visit)
- Changes in score at the Digit Symbol Modalities Test (DSMT)(after 2-years follow up visit)
- Changes in caudate nucleus volume measured at MRI(after 2-years follow up visit)