Relapsing-Remitting Multiple SclerosisNCT00391352
fMRI Study of Treatment Recommendations Comparing Recently Diagnosed Multiple Sclerosis (MS) Patients to Controls
An observational study of Relapsing-Remitting Multiple Sclerosis, run by Waukesha Memorial Hospital at 1 site in United States.
Trial summary
Impaired short term memory, attention and concentration lapses, and slower processing of information occur in up to 40-65% of patients with Multiple Sclerosis (MS). The quality of life of individuals with MS is impacted to the degree with which they experience these symptoms. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Relapsing-Remitting Multiple Sclerosis
- What is being tested?
- IFN-β-1a (Rebif®)
- Type of treatment
- Injection or infusion
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2008to Aug 2012
- Phase
- Observational
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: ProHealth Care, Waukesha Memorial Hospital Neuroscience Center
Who may be able to join
- Written informed consent and HIPAA authorization.
- Age between 18 and 65 years
- Male and female subjects with clinically definite or laboratory-supported definite relapsing-remitting multiple sclerosis in accordance with the refined McDonald • Diagnosed with Relapsing-Remitting Multiple Sclerosis for ≤ 1 year
- Naive to disease-modifying treatments
- Expanded Disability Status Score (EDSS) of 0 to ≤ 5.5, inclusive
- Willingness and ability to comply with the protocol for the duration of the study
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- If female, she must either:
- be post-menopausal or surgically sterilized; or
- use a hormonal contraceptive, intra uterine device, diaphragm with spermicide, or condom with spermicide, for the duration of the study; and
- be neither pregnant nor breast-feeding.
- confirmation that if the subject can still have children, that she is not pregnant must be established by a negative urine pregnancy test within 30 days of Study Day o.
Who cannot join
- Pregnant or lactating women, or women of childbearing potential not using an acceptable method of contraception
- Progressive forms of MS (Primary progressive, Secondary progressive)
- Subjects who have been on DMTs or other previous treatment for MS
- Participation in any other studies involving investigational or marketed products, concomitantly or within 30 days prior to screening
- Treatment with oral or systemic corticosteroids or ACTH within 4 weeks of screening or ongoing chronic treatment with systemic corticosteroids.
- Have taken intravenous immunoglobulin or any other investigational drug or taken part in any experimental procedure in the 6 months prior to screening
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- Psychiatric disorder either unstable or would preclude safe participation in the study
- Cognitive impairment which impairs ability to understand or comply with the protocol procedures
- Significant leucopenia (white blood cell count <0.5 times the lower limit of normal) as assessed during the course of routine standard of care
- Elevated liver function tests (ALT, AST, alkaline phosphatase or total bilirubin >2.5 times the upper limit of normal) as assessed during the course of routine standard of care
- Specific systemic diseases, (including insulin-dependent diabetes, Lyme disease, clinically significant cardiac disease, HIV, HTLV-1, and Hepatitis B or C), or other uncontrolled major medical conditions (depression, seizure disorder) that would interfere with the participant's safety, compliance or evaluation
- Unable and/or unlikely to follow the protocol for any reason
- Alcohol and/or any other drug abuse
- Likelihood of requiring treatment during the study period with drugs not permitted by the study protocol.
- Abnormal baseline clinical findings considered by the investigator to be indicative of conditions that might affect study results
- Subjects whose high-resolution anatomic MR scans reveal the presence of a structural abnormality (other than MS)
- Specific exclusion criteria are required for MRI scanning:
- Ferrous objects within the body
- Pregnancy
- Weight inappropriate for height
- Low visual acuity that cannot be corrected with glasses
- History of claustrophobia
- Standard protocol for monitoring based on FDA approved medication will be followed
Trial locations and contacts
1 site in 1 country.
United States1 site
Waukesha Memorial Hospital ProHealth Care
Waukesha, Wisconsin, 53188
About this study
Official title: A Phase 4, fMRI Study of Treatment Recommendations Comparing Patients Taking IFN-β-1a 44 mcg Tiw SC (Rebif®) to Controls of Patients Recently Diagnosed With Relapsing Remitting Multiple Sclerosis Currently Naive to Disease-Modifying Therapy.
Impaired short term memory, attention and concentration lapses, and slower processing of information occur in up to 40-65% of patients with Multiple Sclerosis (MS). The quality of life of individuals with MS is impacted to the degree with which they experience these symptoms.
There are several medications approved by the United States Food and Drug Administration (FDA) to treat MS symptoms and to modify (slow) disease course. Traditional approaches to determining the effectiveness of medications used in treating MS rely on reports of the number of relapses an individual experiences, as well as standard clinical tests, such as the Kurtzke Expanded Disability Status Scale (EDSS).
This research study will look at whether the functional magnetic resonance imaging (fMRI) scan can be used as a tool for measuring changes in the brain associated with treatment in MS patients. Unlike a typical MRI which provides structural information about the brain, the fMRI provides information about brain activity during performance of cognitive or motor tasks.
Read the detailed description
The development of the immunomodulatory, disease-modifying therapies (DMT) represents a major advance for the treatment of multiple sclerosis (MS). To date, immunomodulatory agents approved for the treatment of MS in the United States include two forms of recombinant interferon-beta (IFN-beta-1a [Avonex, Rebif] and IFN-beta-1b [Betaseron]) and synthetic glatiramer acetate [Copaxone]. These drugs have been shown to favorably alter the natural history of relapsing remitting MS by slowing the progression of disability, reducing relapse rate, and decreasing brain inflammation as measured by MRI. There is evidence that the treatment effects of both IFN-beta and glatiramer acetate are related to their properties in regulating various components of the immune system, in particular, the T cell functions (e.g. proliferation and migratory behavior) and cytokine production.
Though demonstrating clear efficacy on a number of short-term clinical measures, these agents are not cures and most patients with MS continue to experience disease activity in spite of treatment. Over the last ten years, clinicians have become comfortable initiating therapy with DMT. Now, attention is focused on monitoring the results of a chosen therapy and deciding whether or not a patient is responding optimally to treatment. At present, however, clinicians lack criteria for defining optimal response to DMT as well as evidence-based recommendations on how to improve treatment outcomes for individual patients.
Using a recently published model generated by an advisory board from the United States, as a framework, The Canadian Multiple Sclerosis Working Group (CMSWG) developed practical, evidence-based recommendations on how neurologists can assess the status of patients on DMT and decide when it may be necessary to modify treatment in order to optimize outcomes. The CMSWG's recommendations are based on monitoring relapses, neurological progression and MRI activity. These recommendations have yet to be implemented in a prospective, randomized, comparative Phase IV clinical trial.
Traditional measures do not provide critical information about the neural systems that underlie change in behavioral performance. The goal of developing a surrogate biological marker of drug efficacy is to be able to measure the extent to which a drug reaches its intended targeted neural system, and to understand and predict the impact of treatment on existing neuropathology. Ideally, relevant clinical outcome measures should be well correlated with the biomarker.
fMRI is a new tool for noninvasive imaging of human brain function. Without the use of contrast agents, fMRI detects regional MR signal increases that have been hypothesized to reflect decreases in deoxyhemoglobin due to local increases in blood flow/volume during task activation. fMRI has higher spatial and temporal resolution than other existing functional imaging techniques, making it ideal for the study of complex cognitive functions in patient populations.
- Conditions
- Relapsing-Remitting Multiple Sclerosis
- Being tested
- IFN-β-1a (Rebif®)
- Keywords
- Multiple Sclerosis, Disease Modifying Therapy
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IFN-β-1a (Rebif®)Drug
44 mcg Three times a week, subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| MS | MS patient is matched to healthy volunteer Receives: Drug: IFN-β-1a (Rebif®) | |
| Control | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary: Examine the change in task-activated fMRI response as a function of disease modifying therapy assigned to MS as compared to controls
Measured: Week 24
Secondary outcomes (1)
Neuropsychological and Neurological outcome measures.
Measured: Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2006 (estimated)
- Study startFeb 2008
- Primary completionAug 2012
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsing-Remitting 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Waukesha Memorial Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- The Cleveland Clinic
- Investigators
- Michael McCrea, PhD, Principal investigator, Waukesha Memorial HospitalStephen Rao, PhD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00391352
- Sponsor's protocol ID
- MSR12006
- Status last verified
- May 2008
- First submitted
- 19 Oct 2006
- Last updated
- 4 Jun 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 4, fMRI Study of Treatment Recommendations Comparing Patients Taking IFN-β-1a 44 mcg Tiw SC (Rebif®) to Controls of Patients Recently Diagnosed With Relapsing Remitting Multiple Sclerosis Currently Naive to Disease-Modifying Therapy.
- ClinicalTrials.gov ID
- NCT00391352
- Acronym / sponsor ID
- MSR12006
- Conditions
- Relapsing-Remitting Multiple Sclerosis
- Keywords
- Multiple Sclerosis, Disease Modifying Therapy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Waukesha Memorial HospitalUniversity, hospital or other
- Collaborators
- The Cleveland Clinic
- Study start
- Feb 2008
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 23 Oct 2006 (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.
Impaired short term memory, attention and concentration lapses, and slower processing of information occur in up to 40-65% of patients with Multiple Sclerosis (MS). The quality of life of individuals with MS is impacted to the degree with which they experience these symptoms.
There are several medications approved by the United States Food and Drug Administration (FDA) to treat MS symptoms and to modify (slow) disease course. Traditional approaches to determining the effectiveness of medications used in treating MS rely on reports of the number of relapses an individual experiences, as well as standard clinical tests, such as the Kurtzke Expanded Disability Status Scale (EDSS).
This research study will look at whether the functional magnetic resonance imaging (fMRI) scan can be used as a tool for measuring changes in the brain associated with treatment in MS patients. Unlike a typical MRI which provides structural information about the brain, the fMRI provides information about brain activity during performance of cognitive or motor tasks.
Detailed description
The development of the immunomodulatory, disease-modifying therapies (DMT) represents a major advance for the treatment of multiple sclerosis (MS). To date, immunomodulatory agents approved for the treatment of MS in the United States include two forms of recombinant interferon-beta (IFN-beta-1a [Avonex, Rebif] and IFN-beta-1b [Betaseron]) and synthetic glatiramer acetate [Copaxone]. These drugs have been shown to favorably alter the natural history of relapsing remitting MS by slowing the progression of disability, reducing relapse rate, and decreasing brain inflammation as measured by MRI. There is evidence that the treatment effects of both IFN-beta and glatiramer acetate are related to their properties in regulating various components of the immune system, in particular, the T cell functions (e.g. proliferation and migratory behavior) and cytokine production.
Though demonstrating clear efficacy on a number of short-term clinical measures, these agents are not cures and most patients with MS continue to experience disease activity in spite of treatment. Over the last ten years, clinicians have become comfortable initiating therapy with DMT. Now, attention is focused on monitoring the results of a chosen therapy and deciding whether or not a patient is responding optimally to treatment. At present, however, clinicians lack criteria for defining optimal response to DMT as well as evidence-based recommendations on how to improve treatment outcomes for individual patients.
Using a recently published model generated by an advisory board from the United States, as a framework, The Canadian Multiple Sclerosis Working Group (CMSWG) developed practical, evidence-based recommendations on how neurologists can assess the status of patients on DMT and decide when it may be necessary to modify treatment in order to optimize outcomes. The CMSWG's recommendations are based on monitoring relapses, neurological progression and MRI activity. These recommendations have yet to be implemented in a prospective, randomized, comparative Phase IV clinical trial.
Traditional measures do not provide critical information about the neural systems that underlie change in behavioral performance. The goal of developing a surrogate biological marker of drug efficacy is to be able to measure the extent to which a drug reaches its intended targeted neural system, and to understand and predict the impact of treatment on existing neuropathology. Ideally, relevant clinical outcome measures should be well correlated with the biomarker.
fMRI is a new tool for noninvasive imaging of human brain function. Without the use of contrast agents, fMRI detects regional MR signal increases that have been hypothesized to reflect decreases in deoxyhemoglobin due to local increases in blood flow/volume during task activation. fMRI has higher spatial and temporal resolution than other existing functional imaging techniques, making it ideal for the study of complex cognitive functions in patient populations.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MS | – | Drug: IFN-β-1a (Rebif®)MS patient is matched to healthy volunteer |
| Control | – | – |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- ProHealth Care, Waukesha Memorial Hospital Neuroscience Center
Key inclusion criteria (11 listed)
- Written informed consent and HIPAA authorization.
Key exclusion criteria (23 listed)
- Pregnant or lactating women, or women of childbearing potential not using an acceptable method of contraception
- Progressive forms of MS (Primary progressive, Secondary progressive)
- Subjects who have been on DMTs or other previous treatment for MS
- Participation in any other studies involving investigational or marketed products, concomitantly or within 30 days prior to screening
- Treatment with oral or systemic corticosteroids or ACTH within 4 weeks of screening or ongoing chronic treatment with systemic corticosteroids.
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 |
|---|---|---|
| IFN-β-1a (Rebif®)44 mcg Three times a week, subcutaneous injection | Drug | MS |
Primary outcome
Primary: Examine the change in task-activated fMRI response as a function of disease modifying therapy assigned to MS as compared to controls
Time frame: Week 24
1 secondary outcome
Neuropsychological and Neurological outcome measures.
Time frame: Week 24
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 4 Jun 2014.
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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.
Michael McCrea, PhD principal investigator
Waukesha Memorial Hospital
Stephen Rao, PhD principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Relapsing-Remitting Multiple Sclerosis, run by Waukesha Memorial Hospital 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 11 inclusion and 23 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 4 Jun 2014. 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.
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?
Primary: Examine the change in task-activated fMRI response as a function of disease modifying therapy assigned to MS as compared to controls (time frame: Week 24). 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 4 Jun 2014.