Atorvastatin (Lipitor) Therapy in Patients With Clinically Isolated Syndrome (CIS) at Risk for Multiple Sclerosis - Full Text View

Sponsors and Collaborators:	National Institute of Allergy and Infectious Diseases (NIAID) Immune Tolerance Network
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00094172

Purpose

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.

Condition	Intervention	Phase
Multiple Sclerosis	Drug: Atorvastatin Drug: Placebo	Phase II

MedlinePlus related topics: Multiple Sclerosis

Drug Information available for: Atorvastatin Atorvastatin calcium

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	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

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Ability of atorvastatin to decrease or delay clinical and MRI disease activity in patients with clinically isolated syndrome (CIS) and MRI findings suggestive of MS compared with placebo [ Time Frame: Start of study to end of study;18 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Incidence of adverse events [ Time Frame: Start of study to end of study;18 months ] [ Designated as safety issue: Yes ]
time to first treated clinical event typical of MS after randomization [ Time Frame: Start of study to end of study;18 months ] [ Designated as safety issue: Yes ]
proportion of participants who are diagnosed with MS according to the McDonald criteria during treatment phase (Months 1 to 12) and follow-up phase (Months 12 to 18) [ Time Frame: Start of study to end of study;18 months ] [ Designated as safety issue: Yes ]
number of clinical exacerbations [ Time Frame: Start of study to end of study;18 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	152
Study Start Date:	May 2005
Estimated Study Completion Date:	March 2009
Estimated Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: Atorvastatin 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
2: Placebo Comparator	Drug: Placebo tablet form

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00094172

Locations

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

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Immune Tolerance Network

Investigators

Study Chair:	Scott Zamvil, MD, PhD	University of California, San Francisco
Study Chair:	Emmanuelle Waubant, MD, PhD	University of California, San Francisco

More Information

Additional Information:

Click here for the Immune Tolerance Network Web site This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	DAIT/NIAID ( Associate Director, Clinical Research Program )
Study ID Numbers:	ITN020AI
Study First Received:	October 14, 2004
Last Updated:	March 26, 2009
ClinicalTrials.gov Identifier:	NCT00094172 History of Changes
Health Authority:	United States: Food and Drug Administration; United States: Institutional Review Board

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Early Multiple Sclerosis
MS
Clinically Isolated Syndrome

Study placed in the following topic categories:

Antimetabolites
Autoimmune Diseases
Multiple Sclerosis
Demyelinating Diseases
Antilipemic Agents
Demyelinating Autoimmune Diseases, CNS

Sclerosis
Anticholesteremic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Atorvastatin
Autoimmune Diseases of the Nervous System

Additional relevant MeSH terms:

Antimetabolites
Autoimmune Diseases
Disease
Molecular Mechanisms of Pharmacological Action
Demyelinating Diseases
Immune System Diseases
Antilipemic Agents
Nervous System Diseases
Enzyme Inhibitors
Sclerosis

Anticholesteremic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pharmacologic Actions
Multiple Sclerosis
Pathologic Processes
Therapeutic Uses
Syndrome
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Atorvastatin

ClinicalTrials.gov processed this record on May 07, 2009