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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
82
atorvastatin at the dose of 80 mg/day. Participants will be allowed to decrease the daily dose to 40 mg/day if the higher dose is not well-tolerated
tablet form
Barrow Neurological Institute
Phoenix, Arizona, United States
Keck School of Medicine
Los Angeles, California, United States
University of California, San Francisco
San Francisco, California, United States
Yale MS Research Center
New Haven, Connecticut, United States
Johns Hopkins
Baltimore, Maryland, United States
Washington University Multiple Sclerosis Center
St Louis, Missouri, United States
Jacobs Neurological Institute
Buffalo, New York, United States
Mount Sinai School of Medicine
New York, New York, United States
University of Rochester
Rochester, New York, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
...and 4 more locations
The Occurrence of ≥ 3 New T2 Lesions With or Without Gd+ Enhancement or Clinical Exacerbation Through 12 Months.
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
Time frame: 12 months post-randomization
Proportion of Participants Who Are Diagnosed With Multiple Sclerosis According to the McDonald Criteria
Number of participants diagnosed with Multiple Sclerosis (MS) according to the McDonald criteria\[1\] 1. The McDonald criteria uses dissemination in time and space\[2\] established by Magnetic Resonance Image (MRI) findings to provide a clinical diagnosis for MS 2. Dissemination in time is established by a new T2 or gadolinium-enhancing (Gd+) lesion found on a repeat MRI. The presence of any 3 of the following establishes dissemination in space: 1 Gd+ lesion or 9 T2 bright lesions if there is no enhancement; ≥1 infratentorial lesion; ≥1 juxtacortical lesion; ≥3 periventricular lesions
Time frame: 12 months post-randomization
Proportion of Participants Diagnosed With Multiple Sclerosis According to the McDonald Criteria
Number of participants diagnosed with Multiple Sclerosis (MS) according to the McDonald criteria\[1\] 1. The McDonald criteria uses dissemination in time and space\[2\] established by Magnetic Resonance Image (MRI) findings to provide a clinical diagnosis for MS 2. Dissemination in time is established by a new T2 or gadolinium-enhancing (Gd+) lesion found on a repeat MRI. The presence of any 3 of the following establishes dissemination in space: 1 Gd+ lesion or 9 T2 bright lesions if there is no enhancement; ≥1 infratentorial lesion; ≥1 juxtacortical lesion; ≥3 periventricular lesions
Time frame: 18 months post-randomization
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