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.

Condition	Treatment or Intervention	Phase
Multiple Sclerosis Clinically Isolated Syndrome	Drug: Atorvastatin	Phase II

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-day course of intravenously (IV) administered corticosteroids at least 28 days before the start of the study. 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. Certain participants will be offered interferon beta-1a at Month 12. Participants will be instructed to report any change in their health status to their treating physician within 48 hours of the onset of symptoms.

Ages Eligible for Study:  18 Years   -   50 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• 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 48 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

Exclusion Criteria:

• 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

Jeffrey B. Matthews, PhD      604-921-6597    jmatthews@immunetolerance.org

Arizona
      Barrow Neurological Institute, Phoenix,  Arizona,  85013,  United States
California
      University of California, San Francisco, San Francisco,  California,  94143,  United States
      Keck School of Medicine, Los Angeles,  California,  90033,  United States
Connecticut
      Yale MS Research Center, New Haven,  Connecticut,  06510,  United States
Maryland
      Johns Hopkins, Baltimore,  Maryland,  21287,  United States
Massachusetts
      Brigham and Women’s Hospital, Boston,  Massachusetts,  02115,  United States
Missouri
      Washington University Multiple Sclerosis Center, St. Louis,  Missouri,  63110,  United States
New York
      Mount Sinai School of Medicine, New York,  New York,  10029,  United States
      Jacobs Neurological Institute, Buffalo,  New York,  14203,  United States
      University of Rochester, Rochester,  New York,  14642,  United States
Ohio
      Cleveland Clinic Foundation, Cleveland,  Ohio,  44195,  United States
Oregon
      Oregon Health Sciences University, Portland,  Oregon,  97201,  United States
Texas
      University of Texas Southwestern Medical Center, Dallas,  Texas,  75930,  United States
Washington
      Virginia Mason MS Center, Seattle,  Washington,  98111,  United States
Canada, Quebec
      Montreal Neurological Institute, Montreal,  Quebec,  H3A 2B4,  Canada

Study chairs or principal investigators

Scott Zamvil, MD,  Principal Investigator,  University of California, San Francisco   

Study ID Numbers:  ITN020AI
Record last reviewed:  October 2004
Record first received:  October 14, 2004
ClinicalTrials.gov Identifier:  NCT00094172
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2004-11-08