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

This study has been completed.
Sponsor:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00094172
First received: October 14, 2004
Last updated: June 4, 2014
Last verified: June 2014
  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 2

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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • The Occurrence of ≥ 3 New T2 Lesions With or Without Gd+ Enhancement or Clinical Exacerbation Through 12 Months. [ Time Frame: 12 months post-randomization ] [ Designated as safety issue: Yes ]

    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

    1. A new T2 lesion is an abnormal, hyperintense white-matter area visible on T2 weighted images that were not present on the baseline scan
    2. A Gd+ enhancement is defined as a contrast enhancement visible on a new T2 lesion
    3. 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


Secondary Outcome Measures:
  • Proportion of Participants Who Are Diagnosed With Multiple Sclerosis According to the McDonald Criteria [ Time Frame: 12 months post-randomization ] [ Designated as safety issue: Yes ]

    Number of participants diagnosed with Multiple Sclerosis (MS) according to the McDonald criteria[1]

    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
    2. 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

  • Proportion of Participants Diagnosed With Multiple Sclerosis According to the McDonald Criteria [ Time Frame: 18 months post-randomization ] [ Designated as safety issue: Yes ]

    Number of participants diagnosed with Multiple Sclerosis (MS) according to the McDonald criteria[1]

    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
    2. 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


Enrollment: 82
Study Start Date: May 2005
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atorvastatin
80 mg/day
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
Other Name: Lipitor
Placebo Comparator: Placebo 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Keck School of Medicine
Los Angeles, California, United States, 90033
University of California, San Francisco
San Francisco, California, United States, 94143
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
Jacobs Neurological Institute
Buffalo, New York, United States, 14203
Mount Sinai School of Medicine
New York, New York, United States, 10029
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
Immune Tolerance Network (ITN)
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:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00094172     History of Changes
Other Study ID Numbers: DAIT ITN020AI
Study First Received: October 14, 2004
Results First Received: September 29, 2011
Last Updated: June 4, 2014
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

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Atorvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2014