Modifiers of Disease Severity and Progression in Cerebral Cavernous Malformations
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 789
- 试验地点
- 11
- 主要终点
- Total CCM lesion number per patient
研究概览
简要总结
Cerebral cavernous malformations (CCMs) are clusters of abnormal blood vessels in the brain and spine. CCMs can bleed and cause strokes, seizures, and headaches. CCMs are often caused by an inherited gene mutation (alteration) in one of three CCM genes (CCM1, CCM2, or CCM3). There is a wide range of disease severity even among family members with this disease, though the natural history has not been clearly described for this particular population.
This study will continue to enroll and follow participants with familial CCM to identify factors that influence CCM disease severity and progression, focusing on barriers to clinical trial preparedness. Our long-term goal is to identify measurable outcomes and robust biomarkers that will help select high-risk patients and help monitor drug response in future clinical trials.
The specific goals of this study are to:
- Identify factors that influence lesion progression to symptomatic hemorrhage and other outcomes, including quality of life;
- Investigate the role of the gut microbiome and lesion burden in CCM disease, and
- Identify blood biomarkers predictive of CCM disease severity and progression for clinical trials.
详细描述
This study is one of three projects participating in the Brain Vascular Malformation Consortium (BVMC) funded by the Office of Rare Diseases Research, which is part of the National Center for Advancing Translational Sciences (NCATS), and the National Institute of Neurological Disorders and Stroke (NINDS).
The CCM project is a cross-sectional and longitudinal study of familial CCM patients. The study is currently in the third 5-year cycle. During the first 5 year cycle (BVMC1), the CCM project was focused on recruiting CCM1 cases with the common Hispanic mutation (CHM). In the second 5-year cycle (BVMC2), we expanded recruitment to include not only CCM1-CHM cases, but also other CCM familial patients and mutation carriers. In the third 5-year cycle (BVMC3), we will continue to recruit familial CCM cases and expand to additional recruitment sites.
We collect clinical, genetic, imaging, treatment, and outcome data in participants, and follow enrolled participants over time to understand the natural history of this disease.
For new study participants, you will be asked to:
- Give permission for study staff to access your medical records to collect clinical information and to obtain copies of MRI scans and reports.
- Fill out a questionnaire about your quality of life, family history, and medical/surgical history.
- Give a blood and/or saliva sample, and stool sample.
- Give permission to store and use your CCM resected tissue for research (if undergoing surgery).
- Participate in annual follow-ups to update medical, surgical, and neurological information.
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
- •Individual has a CCM mutation confirmed through DNA testing, or
- •Individual meets 2 or more of the following clinical criteria:
- •Clinical diagnosis of CCM
- •Multi-focal CCMs on MRI
- •Family history of CCM
排除标准
- •Individuals who are incarcerated
- •Individuals who are homeless
- •Unable or unwilling to sign the informed consent
结局指标
主要结局
Total CCM lesion number per patient
时间窗: Baseline
The number of lesions (or cavernous angiomas) located in the brain will be counted by a neuroradiologist and by an automated algorithm developed as part of this project.
Rate of symptomatic hemorrhage
时间窗: Baseline and annual assessment
Symptomatic hemorrhage is defined as diagnostic evidence of new lesional bleeding or hemorrhagic growth, in association with directly attributable symptoms. Rate of symptomatic hemorrhage and the factors that influence hemorrhage rates will be assessed.
次要结局
- Change in lesion number(Baseline, Follow up MRI)
- Modified Rankin score(Baseline and annual assessment)