Atorvastatin (Lipitor) Therapy in Patients With Clinically Isolated Syndrome (CIS) at Risk for Multiple Sclerosis
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Multiple Sclerosis
Intervention: Atorvastatin (Drug); Placebo (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s): Scott Zamvil, MD, PhD, Study Chair, Affiliation: University of California, San Francisco Emmanuelle Waubant, MD, PhD, Study Chair, Affiliation: University of California, San Francisco
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.
Clinical Details
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)
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
Primary outcome: The Occurrence of ≥ 3 New T2 Lesions With or Without Gd+ Enhancement or Clinical Exacerbation Through 12 Months.
Secondary outcome: Proportion of Participants Who Are Diagnosed With Multiple Sclerosis According to the McDonald CriteriaProportion of Participants Diagnosed With Multiple Sclerosis According to the McDonald Criteria
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
Minimum age: 18 Years.
Maximum age: 55 Years.
Gender(s): 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 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
Locations and Contacts
Barrow Neurological Institute, Phoenix, Arizona 85013, United States
Keck School of Medicine, Los Angeles, California 90033, United States
University of California, San Francisco, San Francisco, California 94143, United States
Yale MS Research Center, New Haven, Connecticut 06510, United States
Johns Hopkins, Baltimore, Maryland 21287, United States
Washington University Multiple Sclerosis Center, St Louis, Missouri 63110, United States
Jacobs Neurological Institute, Buffalo, New York 14203, United States
Mount Sinai School of Medicine, New York, New York 10029, United States
University of Rochester, Rochester, New York 14642, United States
Cleveland Clinic Foundation, Cleveland, Ohio 44195, United States
Oregon Health Sciences University, Portland, Oregon 97201, United States
Montreal Neurological Institute, Montreal, Quebec H3A 2B4, Canada
University of Texas Southwestern Medical Center, Dallas, Texas 75930, United States
Virginia Mason MS Center, Seattle, Washington 98111, United States
Additional Information
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
Starting date: May 2005
Last updated: June 4, 2014
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