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

Multiple Sclerosis Clinical Trial

— STAYCIS  

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 (ITN020AI)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00094172
• Other study ID #: DAIT ITN020AI
• Status: Completed
• Phase: Phase 2
• First received: October 14, 2004
• Last updated: June 4, 2014
• Start date: May 2005
• Est. completion date: May 2009

Study information

• Verified date: June 2014
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: May 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

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
• Placebo
tablet form

Locations

Country	Name	City	State
Canada	Montreal Neurological Institute	Montreal	Quebec
United States	Johns Hopkins	Baltimore	Maryland
United States	Jacobs Neurological Institute	Buffalo	New York
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Keck School of Medicine	Los Angeles	California
United States	Yale MS Research Center	New Haven	Connecticut
United States	Mount Sinai School of Medicine	New York	New York
United States	Barrow Neurological Institute	Phoenix	Arizona
United States	Oregon Health Sciences University	Portland	Oregon
United States	University of Rochester	Rochester	New York
United States	University of California, San Francisco	San Francisco	California
United States	Virginia Mason MS Center	Seattle	Washington
United States	Washington University Multiple Sclerosis Center	St Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Immune Tolerance Network (ITN)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

Waubant E, Pelletier D, Mass M, Cohen JA, Kita M, Cross A, Bar-Or A, Vollmer T, Racke M, Stüve O, Schwid S, Goodman A, Kachuck N, Preiningerova J, Weinstock-Guttman B, Calabresi PA, Miller A, Mokhtarani M, Iklé D, Murphy S, Kopetskie H, Ding L, Rosenberg — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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; A new T2 lesion is an abnormal, hyperintense white-matter area visible on T2 weighted images that were not present on the baseline scan; A Gd+ enhancement is defined as a contrast enhancement visible on a new T2 lesion; 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	12 months post-randomization	Yes
Secondary	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]; The McDonald criteria uses dissemination in time and space[2] established by Magnetic Resonance Image (MRI) findings to provide a clinical diagnosis for MS; 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	12 months post-randomization	Yes
Secondary	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]; The McDonald criteria uses dissemination in time and space[2] established by Magnetic Resonance Image (MRI) findings to provide a clinical diagnosis for MS; 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	18 months post-randomization	Yes

External Links

•   Click here for the Immune Tolerance Network Web site
•   Immune Tolerance Network (ITN) TrialShare: open public access to participant-level data available for this trial