A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Efficacy and Safety of Atorvastatin in Patients With Clinically Isolated Syndrome and High Risk of Conversion to Multiple Sclerosis (ITN020AI)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 82
- 试验地点
- 14
- 主要终点
- The Occurrence of ≥ 3 New T2 Lesions With or Without Gd+ Enhancement or Clinical Exacerbation Through 12 Months.
研究概览
简要总结
Patients who have been diagnosed with clinically isolated syndrome (CIS) often develop problems related to the central nervous system, which controls the nerves in the body. Some of these patients may later be diagnosed with multiple sclerosis (MS), a progressive disease of the nervous system. The purpose of this study is to determine if the drug atorvastatin is helpful to CIS patients.
Study hypothesis: Early intervention with atorvastatin in patients with CIS will result in a state of immunological tolerance.
详细描述
CIS is a single clinical event indicating temporary disruption of normal nerve function. CIS patients may have a loss of vision in one eye; trouble with balance; double vision; numbness in the face; and tingling, numbness, or weakness in the arms or legs. Some CIS patients may develop MS, but others may not. Studies have shown that when CIS is accompanied by magnetic resonance imaging (MRI)-detected brain lesions that are consistent with those seen in MS, there is a high risk of a second neurologic event and a diagnosis of MS within several years. This study will evaluate the efficacy of atorvastatin, an antihyperlipidemic, in the prevention of MS in CIS patients.
This study will last 18 months. All participants must complete a 3- to 5-day course of corticosteroids at least 28 days before the baseline evaluations. This corticosteroid therapy must be initiated within 60 days of CIS onset. Participants will be randomly assigned to receive 80 mg of either atorvastatin or placebo by mouth daily for 12 months. Study visits will occur at screening and every 3 months thereafter until the end of the 18-month study. Blood collection will occur at selected visits, and other additional evaluations will be performed at Months 1 and 2. Selected participants will undergo MRI brain scans. Participants will be offered interferon beta-1a (Avonex®), free of charge, if they develop disease activity. Participants will be instructed to report any change in their health status to their treating physician within 48 hours of the onset of symptoms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinically isolated syndrome (CIS) as defined by an acute or subacute well-defined neurological event lasting at least 48 hours and consistent with MS (i.e., optic neuritis, spinal cord syndrome, brainstem/cerebellar syndromes). Other causes for optic neuritis other than CIS must be ruled out by an ophthalmologist. Patients with other "clinically silent" abnormal findings found upon neurological examination that are not attributable to the presenting symptom are not excluded.
- •Onset of CIS symptoms occurring within 90 days of randomization
- •Abnormal, unenhanced brain MRI with 2 or more clinically silent T2 lesions greater than or equal to 3 mm in diameter, at least one of which is periventricular in location or ovoid in shape
- •Willing to use acceptable methods of contraception
- •Have received 3 to 5 days of corticosteroid therapy within 60 days of CIS onset
排除标准
- •Definite diagnosis of MS according to McDonald criteria
- •Previous history of neurological symptoms lasting more than 48 hours. Patients with a history of neurological symptoms lasting less than 48 hours will not be excluded.
- •Prior use of interferon, glatiramer acetate, cyclophosphamide, mitoxantrone, or plasmapheresis anytime prior to study entry
- •Use of interferon preparations (unless as specified by the protocol), glatiramer acetate, cyclophosphamide, mitoxantrone, or plasmapheresis during the study
- •Use of cyclosporine, fibric acid derivatives, niacin, erythromycin, or azole antifungal during the study
- •Received more than 5 g of methylprednisolone (or the equivalent of other IV corticosteroid) prior to study screening
- •Use of a cholesterol-lowering agent during the 3 months prior to study screening or need for such agents during the study
- •Previous history of severe side effects with statin therapy
- •Prior exposure to total lymphoid irradiation
- •History of substance abuse in the 12 months prior to study screening
- •History of systemic illness or medical condition that would limit the likelihood of completing the MRI procedures or would interfere with the measurement of a therapeutic effect
- •Implanted pacemakers, cochlear implants, defibrillators, or metallic objects on or inside the body
- •Uncontrolled hypertension, asthma, known malignancy other than skin cancer, symptomatic cardiac disease, epilepsy, insulin-dependent diabetes, or symptoms that can only be explained by systemic lupus erythematosus (SLE) or other autoimmune diseases
- •Active liver disease
- •Major medical illnesses or psychiatric impairment that in the investigator's opinion could interfere with the study
- •History of severe depression or suicidal ideation within 1 year of study entry
- •Pregnancy or breastfeeding
研究组 & 干预措施
Atorvastatin
80 mg/day
干预措施: Atorvastatin (Drug)
Placebo
Once daily.
干预措施: Placebo (Drug)
结局指标
主要结局
The Occurrence of ≥ 3 New T2 Lesions With or Without Gd+ Enhancement or Clinical Exacerbation Through 12 Months.
时间窗: 12 months post-randomization
The occurrence of ≥ T2 lesions\[1\] with or without gadolinium lesion (Gd+) enhancement\[2\] or clinical exacerbation\[3\] through 12 months. A higher score indicates more severe disease 1. A new T2 lesion is an abnormal, hyperintense white-matter area visible on T2 weighted images that were not present on the baseline scan 2. A Gd+ enhancement is defined as a contrast enhancement visible on a new T2 lesion 3. A clinical exacerbation is a new neurological symptom that lasts more than 48 hours in a participant who has been neurologically stable for 30 days following start of study medication
次要结局
- Proportion of Participants Who Are Diagnosed With Multiple Sclerosis According to the McDonald Criteria(12 months post-randomization)
- Proportion of Participants Diagnosed With Multiple Sclerosis According to the McDonald Criteria(18 months post-randomization)