Phase I-II Randomized, Placebo-Controlled, Single-Blinded, Single-Site Clinical Trial of Atorvastatin in the Treatment of Cavernous Angiomas With Symptomatic Hemorrhage Exploratory Proof of Concept (AT CASH EPOC)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Percent Change in Mean Lesional QSM (QSM Change Score)
研究概览
简要总结
This phase I/II randomized, placebo-controlled, double-blinded, single-site clinical trial is designed to investigate the effect of a prolonged course of atorvastatin versus placebo on CCM lesional iron deposition assessed by validated quantitative susceptibility mapping (QSM) MRI studies in patients who suffered a symptomatic bleed within the preceding one year.
详细描述
This phase I/II randomized, placebo-controlled, double-blinded, single-site clinical trial is designed to investigate the effect of a prolonged course of atorvastatin versus placebo on CCM lesional iron deposition assessed by validated quantitative susceptibility mapping (QSM) MRI studies in patients who suffered a symptomatic bleed within the preceding one year. Subjects will also be assessed by lesional and brain vascular permeability MRI using dynamic contrast enhanced quantitative perfusion (DCEQP) and a number of clinical evaluation tools. Subjects shall be followed for 2 years from randomization, the period of highest likelihood of rebleed after a recent CCM hemorrhage. Subjects will undergo clinical and MRI evaluations at baseline, and at 12 and 24 months during the study period. Enrolled subjects and the treating team will be blinded to treatment group allocation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of CCM of any genotype supported by relevant imaging studies.
- •Symptomatic CCM bleeding event within 1 year prior to enrollment.
- •Must be willing/able to travel to the study site for all study visits (baseline, 12 months, and 24 months) over the course of the study period.
排除标准
- •Pre-menopausal women who are breastfeeding, pregnant or likely to get pregnant during the study period.
- •Previous cranial irradiation or surgical/radiosurgical treatment of CCM lesion.
- •Failure to pass MRI safety screening (claustrophobia, metal implant . . . etc)
- •Known allergy or intolerance to gadolinium.
- •Severely impaired renal function (eGFR < 60ml/min), active renal disease or status post-kidney transplants.
- •Statin therapy, for any indication, for more than 7 continuous days or greater than 14 total days within 12 months preceding enrollment.
- •Indication to use statin medication for current approved indication, unrelated to CCM
- •Known allergy or intolerance to statins
- •Liver dysfunction or active liver disease (including chronic viral hepatitis) defined as baseline serum transaminases levels twice the upper range of normal.
- •Previous diagnosis of skeletal muscle disorders of any cause (myopathy), or baseline creatine kinase level five times the upper range of normal.
- •Currently treated with or likely to need treatment with one or more of prohibited medications listed in the protocol.
- •Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- •Serious illness (requiring systemic treatment and/or hospitalization) until subject either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 30 days prior to study entry.
- •Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated, including conditions resulting in or precipitating myopathy (e.g. HIV, uncontrolled hypothyroidism).
- •In the investigator's opinion, the patient is unstable, and would benefit from a specific intervention rather than treatment with atorvastatin.
- •Inability or unwillingness of subject or legal guardian/representative to give written informed consent.
- •No documentation of valid healthcare insurance.
- •No medical record confirmation of primary care physician.
研究组 & 干预措施
Treatment
Atorvastatin 80mg OD (optimal dose). Treatment dose will be de-escalated to 40mg based on reported adverse events.
干预措施: Atorvastatin (Drug)
Placebo
Identically looking capsules containing no active ingredient
干预措施: Placebo (Other)
结局指标
主要结局
Percent Change in Mean Lesional QSM (QSM Change Score)
时间窗: 2 years of follow-up
QSM change score is the Percentage Change in mean lesional iron deposition per year (QSM score) according to assigned treatment (modified intention-to-treat cohort), presented as a mean value across all participants from baseline to year 1 and year 1 to year 2 follow-up MRIs. Quantitative susceptibility mapping (QSM) is a noninvasive MRI technique that assesses iron content by quantifying the magnetic susceptibility of local tissues. A higher QSM value corresponds to a larger amount of iron in the lesion, which means more blood is present in the lesion.
次要结局
- Compare the Changes in Modified Rankin Score Between Atorvastatin and Placebo Groups at the Year 1 Follow-up Visit(1 year of follow-up)
- Compare the Changes in Modified Rankin Score Between Atorvastatin and Placebo Groups at the Year 2 Follow-up Visit.(1 year of follow-up (from year 1 to year 2))
- Mean Score of European Quality of Life Visual Analogue Scale (EQ-VAS) at the Year 2 Follow-up Visit(1 year of follow up (from year 1 to year 2))
- Compare Rate of Drug Compliance in Atorvastatin vs Placebo Group(2 years of follow-up)
- Mean Percent Change in Rho-associated Protein Kinase (ROCK) Activity in Peripheral Blood Leukocytes From Baseline to Year 2(2 year follow-up)
- Percent Change in Dynamic Contrast-enhanced Quantitative Perfusion (DCEQP) Value (Vascular Permeability) in Index Lesion (Lesional DCEQP Change Score)(2 years of follow-up)
- Mean Score of European Quality of Life Visual Analogue Scale (EQ-VAS) at the Year 1 Follow-up Visit.(1 year of follow up)
- Mean Percent Change in Rho-associated Protein Kinase (ROCK) Activity in Peripheral Blood Leukocytes From Baseline to Year 1(1 year of follow-up)