Atorvastatin (Lipitor) Therapy in Patients With Clinically Isolated Syndrome (CIS) at Risk for Multiple Sclerosis (STAYCIS)
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| ClinicalTrials.gov Identifier: NCT00094172 |
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Recruitment Status :
Completed
First Posted : October 15, 2004
Results First Posted : November 3, 2011
Last Update Posted : April 28, 2017
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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 or disease | Intervention/treatment | Phase |
|---|---|---|
| Multiple Sclerosis | Drug: Atorvastatin Drug: Placebo | Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 82 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, 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) |
| Study Start Date : | May 2005 |
| Actual Primary Completion Date : | May 2009 |
| Actual Study Completion Date : | May 2009 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Atorvastatin
80 mg/day
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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 |
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Placebo Comparator: Placebo
Once daily.
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Drug: Placebo
tablet form
Other Name: Placebo Treatment |
- The Occurrence of ≥ 3 New T2 Lesions With or Without Gd+ Enhancement or Clinical Exacerbation Through 12 Months. [ Time Frame: 12 months post-randomization ]
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
- Proportion of Participants Who Are Diagnosed With Multiple Sclerosis According to the McDonald Criteria [ Time Frame: 12 months post-randomization ]
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
- Proportion of Participants Diagnosed With Multiple Sclerosis According to the McDonald Criteria [ Time Frame: 18 months post-randomization ]
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
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, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 55 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00094172
| 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 | |
| Study Chair: | Scott Zamvil, MD, PhD | University of California, San Francisco | |
| Study Chair: | Emmanuelle Waubant, MD, PhD | University of California, San Francisco |
Study Data/Documents: Individual Participant Data Set
ImmPort study identifier is SDY547. ImmPort is the long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
ImmPort study identifier is SDY547
TrialShare is the research portal of the Immune Tolerance Network (ITN) that makes data from the consortium's studies publicly available.
Publications of Results:
| Responsible Party: | National Institute of Allergy and Infectious Diseases (NIAID) |
| ClinicalTrials.gov Identifier: | NCT00094172 |
| Other Study ID Numbers: |
DAIT ITN020AI |
| First Posted: | October 15, 2004 Key Record Dates |
| Results First Posted: | November 3, 2011 |
| Last Update Posted: | April 28, 2017 |
| Last Verified: | March 2017 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Data access is provided to the public in: 1.) the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts that also provides data analysis tools available to researchers; and 2.) TrialShare, the Immune Tolerance Network (ITN) Clinical Trials Research Portal that makes data from the consortium's clinical trials available to the public. |
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Early Multiple Sclerosis MS Clinically Isolated Syndrome |
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Multiple Sclerosis Sclerosis Pathologic Processes Demyelinating Autoimmune Diseases, CNS Autoimmune Diseases of the Nervous System Nervous System Diseases Demyelinating Diseases Autoimmune Diseases Immune System Diseases |
Atorvastatin Anticholesteremic Agents Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents Hydroxymethylglutaryl-CoA Reductase Inhibitors Enzyme Inhibitors |