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

NCT ID: NCT00094172

Last Updated: 2017-04-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-05-31
• Study Completion Date: 2009-05-31

Brief Summary

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.

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.

Conditions

Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Atorvastatin

80 mg/day

Group Type: EXPERIMENTAL

Atorvastatin

Intervention Type: DRUG

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

Placebo

Once daily.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

tablet form

Interventions

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

Intervention Type: DRUG

Placebo

tablet form

Intervention Type: DRUG

Other Intervention Names

Lipitor; Placebo Treatment

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Immune Tolerance Network (ITN)

NETWORK

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Scott Zamvil, MD, PhD

Role: STUDY_CHAIR

University of California, San Francisco

Emmanuelle Waubant, MD, PhD

Role: STUDY_CHAIR

University of California, San Francisco

Locations

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

Oregon Health Sciences University

Portland, Oregon, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Virginia Mason MS Center

Seattle, Washington, United States

Montreal Neurological Institute

Montreal, Quebec, Canada

Countries

United States; Canada

References

Waubant E, Pelletier D, Mass M, Cohen JA, Kita M, Cross A, Bar-Or A, Vollmer T, Racke M, Stuve O, Schwid S, Goodman A, Kachuck N, Preiningerova J, Weinstock-Guttman B, Calabresi PA, Miller A, Mokhtarani M, Ikle D, Murphy S, Kopetskie H, Ding L, Rosenberg E, Spencer C, Zamvil SS; ITN STAyCIS Study Group; ITN020AI Study Management Team. Randomized controlled trial of atorvastatin in clinically isolated syndrome: the STAyCIS study. Neurology. 2012 Apr 10;78(15):1171-8. doi: 10.1212/WNL.0b013e31824f7fdd. Epub 2012 Mar 28.

Reference Type: RESULT

PMID: 22459680 (View on PubMed)

Study Documents

Document Type: Individual Participant Data Set

TrialShare study identifier is ITN020AI

View Document

Document Type: Study overview with synopsis, -navigator, -schedule of assessments, data and reports, -manuscripts and abstracts et al.

TrialShare is the research portal of the Immune Tolerance Network (ITN) that makes data from the consortium's studies publicly available.

View Document

Related Links

https://www.niaid.nih.gov/

National Institute of Allergy and Infectious Diseases (NIAID) website

http://www.immunetolerance.org

Immune Tolerance Network website

Other Identifiers

DAIT ITN020AI

Identifier Type: -

Identifier Source: org_study_id