Multiple SclerosisPhase 4NCT00146068
EARLY IFNB-1a and Simvastatin Combination Therapy in Clinically Isolated Syndrome Suggestive of Multiple Sclerosis
A Phase 4 study testing Avonex/Zocor in people with Multiple Sclerosis, run by University of North Carolina at 1 site in United States.
Trial summary
The purpose of this study is to determine the safety, tolerability and efficacy of a combination therapy interferon beta-1a(Avonex) plus simvastatin (Zocor) vs. interferon beta-1a plus placebo in patients with clinically isolated syndrome suggestive of Multiple Sclerosis. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Avonex/Zocor
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2004to Dec 2007
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Subject has a diagnosis of CIS suggestive of MS involving optic nerve (unilateral optic neuritis), spinal cord (incomplete transverse myelitis), brain stem or cerebellum syndrome confirmed by ophthalmologic or neurological examinations. (Onset of CIS symptoms must occur within twelve months of randomization).
- At baseline, subject will be between the ages of 18 and 60, inclusive.
- Subject has a baseline EDSS score between 0.0 and 5.5, inclusive.
- MRI findings on the brain scan should reveal at least three out the four following findings: one Gd-enhancing lesion or nine T2 hyperintense lesions; or at least one infratentorial lesion; or at least one juxtacortical lesion and or at least three periventricular lesions.
- Subject has signed informed consent and HIPAA forms.
Who cannot join
- Subject has a diagnosis of CD RRMS according to Poser criteria, definitive MS according McDonald criteria, secondary progressive, or primary progressive MS.
- Subject has been treated with statins in the previous three months. Subject has history of severe side effects related to statin therapy.
- Subject has had a clinically significant infectious illness (e.g., cellulitis, abscess, pneumonia, septicemia) within 30 days prior to randomization.
- Subject has a history of, or abnormal laboratory results indicative of, any significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, gastrointestinal, dermatologic, psychiatric, renal, and/or other major disease.
- Subject has a history of severe allergic or anaphylactic reactions or known drug hypersensitivity.
- Subject has an abnormal screening blood test, performed at the screening visit, exceeding any of the limits defined below:
Show all 37Show fewer
- alanine transaminase (ALT) or aspartate transaminase (AST) > 1.5 times the upper limit of normal (1.5x ULN)
- total white blood cell count < 2,300/mm^3
- CPK level > 2 x ULN on two consecutive occasions tested at least one week apart.
- Platelets less than 150,00/mm3
- Creatinine > 1.5mg/dl.
- prothrombin time (PT) > ULN
- Subject has history of treatment with either interferon-beta 1a or 1b, or glatiramer acetate.
- Subject has had any prior treatment with any of the following medications:
- total lymphoid irradiation
- intravenous immunoglobulins IVIg, or plasma exchange
- natalizumab or any other therapeutic monoclonal antibody
- Subject has had treatment with any of the following medications within 1 year prior to randomization:
- mitoxantrone
- cyclophosphamide
- Subject has had treatment with any of the following medications:
- cyclosporine
- azathioprine
- methotrexate
- glatiramer acetate
- interferon beta-1b or INF beta-1a
- intravenous immunoglobulin (IVIG)
- plasmapheresis or cytapheresis
- Subject has had treatment with any of the following medications within 50 days prior to randomization:
- intravenous corticosteroid treatment
- oral corticosteroid treatment
- Subject has a history of alcohol abuse within 2 years prior to randomization.
- Subject is a female who is not postmenopausal for at least one year, surgically sterile, or willing to practice effective contraception (as defined by the investigator) during the study. The rhythm method is not to be used as the sole method of contraception.
- Subject is a nursing mother, pregnant woman, or planning to become pregnant while on study.
- Subject has had participation in any other investigational study within 6 months prior to randomization.
- Subject is unwilling or is unable to comply with the requirements of this protocol including the presence of any condition (physical, mental, or social) that is likely to affect the subject's ability to comply with the study protocol.
- Subject is determined unsuitable for enrollment into this study for any other reason in the opinion of the Investigator and/or the Sponsor.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of North Carolina-Chapel Hill MS clinic within the Neuroscience Hospital
Chapel Hill, North Carolina, 27599
About this study
Official title: Phase IV Double-Blind Randomized Study to Evaluate Safety and Efficacy of Interferon Beta-1a (Avonex) Plus Simvastatin (Zocor) Combination Therapy in Clinically Isolated Syndrome Suggestive of Multiple Sclerosis Over a One Year Period
The purpose of this study is to determine the safety, tolerability and efficacy of a combination therapy interferon beta-1a(Avonex) plus simvastatin (Zocor) vs. interferon beta-1a plus placebo in patients with clinically isolated syndrome suggestive of Multiple Sclerosis.
Read the detailed description
Interferon beta-1a (IFNB-1a), a FDA approved therapy for relapsing-remitting (RR) MS has several mechanisms of action. It lowers proinflammatory cytokine production and inhibits antigen presentation by class II major histocompatibility complex (MHC) molecule. It also reduces metalloproteinase activity, which all lead to decreased migration of T-lymphocytes into the central nervous system (CNS), and subsequent inhibition of inflammatory lesion formation. We propose that combination therapy during early stages of the disease with second immunomodulatory agent that targets different steps in the pathogenesis of the disease may add to the effectiveness of IFNB-1a. IFNB-1a administered intramuscularly at 30 mg per week is particularly suitable for combination therapy due to its proven efficacy in Clinically Isolated Syndrome (CIS),favorable safety profile and low frequency of neutralizing antibodies (NABs) against IFNB-1a in comparison to other forms of IFNB-1a. Recent studies have reported a significant anti-inflammatory and neuroprotective effects of statins, cholesterol-lowering agents. Statins disrupt cellular membrane lipid rafts, which inhibit the clustering of T-cell receptor (TCR), co-stimulatory, and adhesion molecules, required for optimal T-cell activation. Along with inhibiting T-cell activation, statins decrease IFNB inducible MHC class II expression, suppressing an effective antigen presentation. They block migration of activated mononuclear cells from peripheral circulation into the CNS by blocking LFA-1 adhesion molecule and by reducing metalloproteinase type 9 secretion. While their anti-inflammatory effects at tolerable oral doses may not justify their use as monotherapy for RR MS, their pleiotropic mechanisms of action showed synergistic effects with IFNB-1a in studies in vitro. We propose that simvastatin may enhance the immunomodulatory effects of INFB-1a in patients with CIS suggestive of MS and that this combination may even more effectively prevent further disease activity if administered early in the course of the disease.
- Conditions
- Multiple Sclerosis
- Being tested
- Avonex/Zocor
- Keywords
- 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.
Avonex/ZocorDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary objective of this study is to determine whether combination therapy with IFNb-1a plus simvastatin, when compared to IFNb-1a plus placebo decreases or delays additional clinical or MRI activity.
We will use the following outcome measures:
Relapse rates, Time to first relapse,Number of new T2 lesions, Number of new Gd-enhancing lesions
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2005 (estimated)
- Study startSep 2004
- Primary completionDec 2007
- Study completionDec 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 30 participants
Sponsor and investigators
- Lead sponsor
- University of North Carolina
- Sponsor type
- University, hospital or other
- Investigators
- Silva Markovic-Plese, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00146068
- Sponsor's protocol ID
- 04-NEUR-387
- Status last verified
- Feb 2008
- First submitted
- 1 Sep 2005
- Last updated
- 5 Mar 2008
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IV Double-Blind Randomized Study to Evaluate Safety and Efficacy of Interferon Beta-1a (Avonex) Plus Simvastatin (Zocor) Combination Therapy in Clinically Isolated Syndrome Suggestive of Multiple Sclerosis Over a One Year Period
- ClinicalTrials.gov ID
- NCT00146068
- Acronym / sponsor ID
- 04-NEUR-387
- Conditions
- Multiple Sclerosis
- Keywords
- Clinically Isolated Syndrome
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants
- Lead sponsor
- University of North CarolinaUniversity, hospital or other
- Study start
- Sep 2004
- Primary completion
- Dec 2007 (actual)
- Study completion
- Dec 2007 (actual)
- First posted
- 5 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the safety, tolerability and efficacy of a combination therapy interferon beta-1a(Avonex) plus simvastatin (Zocor) vs. interferon beta-1a plus placebo in patients with clinically isolated syndrome suggestive of Multiple Sclerosis.
Detailed description
Interferon beta-1a (IFNB-1a), a FDA approved therapy for relapsing-remitting (RR) MS has several mechanisms of action. It lowers proinflammatory cytokine production and inhibits antigen presentation by class II major histocompatibility complex (MHC) molecule. It also reduces metalloproteinase activity, which all lead to decreased migration of T-lymphocytes into the central nervous system (CNS), and subsequent inhibition of inflammatory lesion formation. We propose that combination therapy during early stages of the disease with second immunomodulatory agent that targets different steps in the pathogenesis of the disease may add to the effectiveness of IFNB-1a. IFNB-1a administered intramuscularly at 30 mg per week is particularly suitable for combination therapy due to its proven efficacy in Clinically Isolated Syndrome (CIS),favorable safety profile and low frequency of neutralizing antibodies (NABs) against IFNB-1a in comparison to other forms of IFNB-1a. Recent studies have reported a significant anti-inflammatory and neuroprotective effects of statins, cholesterol-lowering agents. Statins disrupt cellular membrane lipid rafts, which inhibit the clustering of T-cell receptor (TCR), co-stimulatory, and adhesion molecules, required for optimal T-cell activation. Along with inhibiting T-cell activation, statins decrease IFNB inducible MHC class II expression, suppressing an effective antigen presentation. They block migration of activated mononuclear cells from peripheral circulation into the CNS by blocking LFA-1 adhesion molecule and by reducing metalloproteinase type 9 secretion. While their anti-inflammatory effects at tolerable oral doses may not justify their use as monotherapy for RR MS, their pleiotropic mechanisms of action showed synergistic effects with IFNB-1a in studies in vitro. We propose that simvastatin may enhance the immunomodulatory effects of INFB-1a in patients with CIS suggestive of MS and that this combination may even more effectively prevent further disease activity if administered early in the course of the disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Subject has a diagnosis of CIS suggestive of MS involving optic nerve (unilateral optic neuritis), spinal cord (incomplete transverse myelitis), brain stem or cerebellum syndrome confirmed by ophthalmologic or neurological examinations. (Onset of CIS symptoms must occur within twelve months of randomization).
- At baseline, subject will be between the ages of 18 and 60, inclusive.
- Subject has a baseline EDSS score between 0.0 and 5.5, inclusive.
- MRI findings on the brain scan should reveal at least three out the four following findings: one Gd-enhancing lesion or nine T2 hyperintense lesions; or at least one infratentorial lesion; or at least one juxtacortical lesion and or at least three periventricular lesions.
- Subject has signed informed consent and HIPAA forms.
Key exclusion criteria (37 listed)
- Subject has a diagnosis of CD RRMS according to Poser criteria, definitive MS according McDonald criteria, secondary progressive, or primary progressive MS.
- Subject has been treated with statins in the previous three months. Subject has history of severe side effects related to statin therapy.
- Subject has had a clinically significant infectious illness (e.g., cellulitis, abscess, pneumonia, septicemia) within 30 days prior to randomization.
- Subject has a history of, or abnormal laboratory results indicative of, any significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, gastrointestinal, dermatologic, psychiatric, renal, and/or other major disease.
- Subject has a history of severe allergic or anaphylactic reactions or known drug hypersensitivity.
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 |
|---|---|---|
| Avonex/Zocor | Drug | – |
Primary outcome
The primary objective of this study is to determine whether combination therapy with IFNb-1a plus simvastatin, when compared to IFNb-1a plus placebo decreases or delays additional clinical or MRI activity.
We will use the following outcome measures:
Relapse rates, Time to first relapse,Number of new T2 lesions, Number of new Gd-enhancing lesions
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2008.
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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.
Silva Markovic-Plese principal investigator
University of North Carolina, Chapel Hill
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Avonex/Zocor in people with Multiple Sclerosis, run by University of North Carolina at 1 site in United States.
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 37 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 5 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 primary objective of this study is to determine whether combination therapy with IFNb-1a plus simvastatin, when compared to IFNb-1a plus placebo decreases or delays additional clinical or MRI activity.. The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Mar 2008.