Multiple SclerosisPhase 2STAYCISNCT00094172
Atorvastatin (Lipitor) Therapy in Patients With Clinically Isolated Syndrome (CIS) at Risk for Multiple Sclerosis
A Phase 2 study testing Atorvastatin in people with Multiple Sclerosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 14 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Atorvastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 82 participants
- Where
- 14 sitesin 2 countries
- Study dates
- May 2005to May 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 17Show fewer
- 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
Trial locations and contacts
14 sites in 2 countries.
14 sites in 2 countries
United States13 sites
Johns Hopkins
Baltimore, Maryland, 21287
Jacobs Neurological Institute
Buffalo, New York, 14203
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
University of Texas Southwestern Medical Center
Dallas, Texas, 75930
Keck School of Medicine
Los Angeles, California, 90033
Yale MS Research Center
New Haven, Connecticut, 06510
Mount Sinai School of Medicine
New York, New York, 10029
Barrow Neurological Institute
Phoenix, Arizona, 85013
Oregon Health Sciences University
Portland, Oregon, 97201
University of Rochester
Rochester, New York, 14642
University of California, San Francisco
San Francisco, California, 94143
Virginia Mason MS Center
Seattle, Washington, 98111
Washington University Multiple Sclerosis Center
St Louis, Missouri, 63110
About this study
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)
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.
Read the 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
- Being tested
- Atorvastatin, Placebo
- Keywords
- Early Multiple Sclerosis, MS, Clinically Isolated Syndrome
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtorvastatinDrug
Also called Lipitor
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
PlaceboDrug
Also called Placebo Treatment
tablet form
| Study group | Role | What they receive |
|---|---|---|
| Atorvastatin | Experimental | 80 mg/day Receives: Drug: Atorvastatin |
| Placebo | Placebo comparator | Once daily. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 months post-randomization
Secondary outcomes (2)
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
Measured: 12 months post-randomization
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
Measured: 18 months post-randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2004 (estimated)
- Study startMay 2005
- Primary completionMay 2009
- Study completionMay 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Immune Tolerance Network (ITN)
- Responsible party
- Sponsor
- Investigators
- Scott Zamvil, MD, PhD, Study chair, University of California, San FranciscoEmmanuelle Waubant, MD, PhD, Study chair, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00094172
- Sponsor's protocol ID
- DAIT ITN020AI
- Acronym
- STAYCIS
- Status last verified
- Mar 2017
- First submitted
- 14 Oct 2004
- Last updated
- 28 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 22459680
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00094172
- Acronym / sponsor ID
- STAYCIS / DAIT ITN020AI
- Conditions
- Multiple Sclerosis
- Keywords
- Early Multiple Sclerosis, MS, Clinically Isolated Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Immune Tolerance Network (ITN)
- Study start
- May 2005
- Primary completion
- May 2009 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 15 Oct 2004 (estimated)
- Results
- Posted 3 Nov 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Atorvastatin | Experimental | Drug: Atorvastatin80 mg/day |
| Placebo | Placebo comparator | Drug: PlaceboOnce daily. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AtorvastatinAlso: Lipitoratorvastatin 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 | Drug | Atorvastatin |
| PlaceboAlso: Placebo Treatmenttablet form | Drug | Placebo |
Primary outcome
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 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
2 secondary outcomes
Proportion of Participants Who Are Diagnosed With Multiple Sclerosis According to the McDonald Criteria
Time frame: 12 months post-randomization
Proportion of Participants Diagnosed With Multiple Sclerosis According to the McDonald Criteria
Time frame: 18 months post-randomization
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22459680Waubant 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.
- National Institute of Allergy and Infectious Diseases (NIAID) websiteLink provided by the sponsor.
- Immune Tolerance Network websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott Zamvil, MD, PhD study chair
University of California, San Francisco
Emmanuelle Waubant, MD, PhD study chair
University of California, San Francisco
14 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Atorvastatin in people with Multiple Sclerosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 14 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Nov 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Occurrence of ≥ 3 New T2 Lesions With or Without Gd+ Enhancement or Clinical Exacerbation Through 12 Months. (time frame: 12 months post-randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00094172, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2017.