Multiple SclerosisNCT00325988
Biomarkers in Multiple Sclerosis
An observational study of Multiple Sclerosis, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
This study will identify biomarkers (genes and proteins) in patients with relapsing-remitting multiple sclerosis (MS) and link them with clinical disease parameters, such as the extent of inflammation and rate of disease progression, to try to better understand the disease. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Multiple Sclerosis
- How many people
- 858 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Dec 2004to 3 Feb 2014
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- To be eligible for entry into this study, candidates must meet the following eligibility criteria at the time of enrollment:
- Between the ages of 18 and 60 years, inclusive.
- Diagnosis of Relapsing-Remitting MS.
- Expanded Disability Status Scale (EDSS) score between 0 and 5.5, inclusive.
- At least 2 exacerbations in the prior three years; one exacerbation may utilize the McDonald MRI criteria for dissemination in time (a new Gd-enhancing lesion demonstrated on a scan done at least 3 months following onset of a clinical attack or a new T2 lesion or Gd-enhancing lesions on a follow-up scan after an additional 3 months).
- Give written informed consent prior to any testing under this protocol, including screening tests and evaluations that are not considered part of the subject's routine care.
- 18 to 60 years inclusive.
Who cannot join
- Candidates will be excluded from study entry if any of the following exclusion criteria exist at the time of screening (prior to randomization):
- Prior use of interferon beta or glatiramer acetate.
- Acute exacerbation within 30 days of screening.
- Steroids for acute exacerbations (greater than 100 mg/day) within 30 days of study entrance or chronic systemic steroid use.
- Evidence of progressive MS.
- Use of immunosuppressive or chemotherapeutic agents or IVIg.
Show all 28Show fewer
- Inability to perform the MSFC (Time 25-Foot Walk, 9HPT, and PASAT3).
- Inability to undergo baseline MRI scan.
- History of any significant cardiac, hepatic, pulmonary, or renal disease; immune deficiency; or other medical conditions that would preclude therapy with interferon beta or glatiramer acetate.
- Known history of sensitivity to gadopentate dimeglumine or mannitol.
- History of a seizure within the 3 months prior to randomization.
- History of suicidal ideation or an episode of severe depression within the 3 months prior to randomization.
- Abnormal screening blood tests exceeding any of the limits defined below:
- Alanine transaminase (ALT) or aspartate transaminase (AST) greater than two times the upper limit of normal (i.e., greater than 2 times the ULN).
- Total white blood cell count less than 2,300/mm(3).
- Platelet count less than 80,000/mm(3).
- Creatinine greater than 2 times the ULN.
- Participation in another experimental clinical trial, without formal approval.
- Previous participation after randomization in this study.
- History of alcohol or drug abuse within the 2 years prior to randomization.
- Female subjects who are currently pregnant, breast-feeding, or plan to become pregnant.
- For female subjects, unless postmenopausal or surgically sterile, unwillingness 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.
- Unwillingness or inability to comply with the requirements of this protocol including the presence of any condition that is likely to affect the subject's returning for scheduled follow-up visits on schedule (any physical, mental, or social condition, including history of any episode of suicidal ideation or severe depression defined as any episode that required hospitalization within the previous 3 months).
- Any significant acute or chronic illness, particularly no autoimmune or chronic inflammatory, -infectious disease.
- HIV positive.
- No treatment with immunomodulatory, immunosuppressive or chemotherapeutic drugs.
- Pregnancy.
- Nursing mothers.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: NINDS Biomarkers in Multiple Sclerosis Study (BioMS)
This study will identify biomarkers (genes and proteins) in patients with relapsing-remitting multiple sclerosis (MS) and link them with clinical disease parameters, such as the extent of inflammation and rate of disease progression, to try to better understand the disease. It will examine how the biomarkers may be related to disease development and progression and differences among patients' symptoms and response to treatment.
Patients with relapsing-remitting MS between 18 and 60 years of age who are enrolled in the multi-institutional MS-CombiRx trial may be eligible for this sub-study. Participants have blood tests when they enter the MS-CombiRx study and again after 6 months, 1 year, and 3 years for analysis for genetic and protein analysis.
Read the detailed description
OBJECTIVE: To identify biomarkers (by gene- and protein expression profiling, single nucleotide polymorphism (SNP) haplotype determination, HLA typing) and link these with clinical- and MRI phenotypes in a large cohort of relapsing-remitting (RR-) MS patients. To identify biomarkers that separate MS patients and healthy, matched controls.
STUDY POPULATION: Up to 1000 patients who are enrolled in and treated under a multi-center trial of combination therapy (MS-CombiRx) using two approved disease-modifying therapies (interferon-beta, IFN-b, Avonex; glatiramer-acetate, GA) as single treatments or in combination. 200 healthy, matched control individuals.
DESIGN: Samples of serum and white blood cells will be obtained on each patient prior to randomization in the MS-CombiRx study and then at 6 months 1, and 3 years following randomization. Samples will be analyzed for SNP haplotype, gene and protein expression, and HLA haplotype. Samples from controls will be analyzed in the same fashion, however, only one time point will be analyzed, and there will be no treatment of controls.
OUTCOME MEASURES: The results of the biomarker studies will be assessed in relationship to both the clinical and MRI phenotype at baseline and to change in disability, relapse rate, response to therapy and change in MRI measures of disease during the 3-year treatment period. Each of the biomarker study components will be analyzed with respect to biomarkers that discriminate between MS patients and controls.
SIGNIFICANCE: Similar to rheumatoid arthritis or autoimmune diabetes multiple sclerosis (MS) is considered a complex disease with autoimmune pathogenesis as well as vulnerability of the target tissue, i.e. the central nervous system (CNS). The results of the biomarker study should provide a better understanding of the disease pathogenesis, of the inter-individual disease heterogeneity, and finally identify biomarkers such as gene- and protein expression signatures and individual genes and proteins that are correlated with responsiveness or non-responsiveness to single drug treatment or the combination of the two drugs. The three years duration of the combination therapy trial will further allow us to gather information on the longitudinal evolution of the identified biomarkers under treatment of MS.
- Conditions
- Multiple Sclerosis
- Keywords
- Neuroimmunology, Demyelinating Disease, Genetics, Proteins
- Medical subject headings
- Multiple Sclerosis, Demyelinating Diseases
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2006 (estimated)
- Study start17 Dec 2004
- Study completion3 Feb 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- 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
- Observational
- Enrolment
- 858 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)
- Sponsor type
- US National Institutes of Health
- Investigators
- Steven Jacobson, Ph.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00325988
- Sponsor's protocol ID
- 050063
- Other IDs
- 05-N-0063
- Status last verified
- 3 Feb 2014
- First submitted
- 15 May 2006
- Last updated
- 17 Dec 2019
- Results posted
- No
Publications
Wynn DR, Rodriguez M, O'Fallon WM, Kurland LT. A reappraisal of the epidemiology of multiple sclerosis in Olmsted County, Minnesota. Neurology. 1990 May;40(5):780-6. doi: 10.1212/wnl.40.5.780.
PubMed 2082944Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med. 2000 Sep 28;343(13):938-52. doi: 10.1056/NEJM200009283431307. No abstract available.
PubMed 11006371Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology. 1996 Apr;46(4):907-11. doi: 10.1212/wnl.46.4.907.
PubMed 8780061
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NINDS Biomarkers in Multiple Sclerosis Study (BioMS)
- ClinicalTrials.gov ID
- NCT00325988
- Acronym / sponsor ID
- 050063
- Conditions
- Multiple Sclerosis
- Keywords
- Neuroimmunology, Demyelinating Disease, Genetics, Proteins
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 858 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 17 Dec 2004
- Study completion
- 3 Feb 2014
- First posted
- 15 May 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.
This study will identify biomarkers (genes and proteins) in patients with relapsing-remitting multiple sclerosis (MS) and link them with clinical disease parameters, such as the extent of inflammation and rate of disease progression, to try to better understand the disease. It will examine how the biomarkers may be related to disease development and progression and differences among patients' symptoms and response to treatment.
Patients with relapsing-remitting MS between 18 and 60 years of age who are enrolled in the multi-institutional MS-CombiRx trial may be eligible for this sub-study. Participants have blood tests when they enter the MS-CombiRx study and again after 6 months, 1 year, and 3 years for analysis for genetic and protein analysis.
Detailed description
OBJECTIVE: To identify biomarkers (by gene- and protein expression profiling, single nucleotide polymorphism (SNP) haplotype determination, HLA typing) and link these with clinical- and MRI phenotypes in a large cohort of relapsing-remitting (RR-) MS patients. To identify biomarkers that separate MS patients and healthy, matched controls.
STUDY POPULATION: Up to 1000 patients who are enrolled in and treated under a multi-center trial of combination therapy (MS-CombiRx) using two approved disease-modifying therapies (interferon-beta, IFN-b, Avonex; glatiramer-acetate, GA) as single treatments or in combination. 200 healthy, matched control individuals.
DESIGN: Samples of serum and white blood cells will be obtained on each patient prior to randomization in the MS-CombiRx study and then at 6 months 1, and 3 years following randomization. Samples will be analyzed for SNP haplotype, gene and protein expression, and HLA haplotype. Samples from controls will be analyzed in the same fashion, however, only one time point will be analyzed, and there will be no treatment of controls.
OUTCOME MEASURES: The results of the biomarker studies will be assessed in relationship to both the clinical and MRI phenotype at baseline and to change in disability, relapse rate, response to therapy and change in MRI measures of disease during the 3-year treatment period. Each of the biomarker study components will be analyzed with respect to biomarkers that discriminate between MS patients and controls.
SIGNIFICANCE: Similar to rheumatoid arthritis or autoimmune diabetes multiple sclerosis (MS) is considered a complex disease with autoimmune pathogenesis as well as vulnerability of the target tissue, i.e. the central nervous system (CNS). The results of the biomarker study should provide a better understanding of the disease pathogenesis, of the inter-individual disease heterogeneity, and finally identify biomarkers such as gene- and protein expression signatures and individual genes and proteins that are correlated with responsiveness or non-responsiveness to single drug treatment or the combination of the two drugs. The three years duration of the combination therapy trial will further allow us to gather information on the longitudinal evolution of the identified biomarkers under treatment of MS.
Study design
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- To be eligible for entry into this study, candidates must meet the following eligibility criteria at the time of enrollment:
- Between the ages of 18 and 60 years, inclusive.
- Diagnosis of Relapsing-Remitting MS.
- Expanded Disability Status Scale (EDSS) score between 0 and 5.5, inclusive.
- At least 2 exacerbations in the prior three years; one exacerbation may utilize the McDonald MRI criteria for dissemination in time (a new Gd-enhancing lesion demonstrated on a scan done at least 3 months following onset of a clinical attack or a new T2 lesion or Gd-enhancing lesions on a follow-up scan after an additional 3 months).
Key exclusion criteria (28 listed)
- Candidates will be excluded from study entry if any of the following exclusion criteria exist at the time of screening (prior to randomization):
- Prior use of interferon beta or glatiramer acetate.
- Acute exacerbation within 30 days of screening.
- Steroids for acute exacerbations (greater than 100 mg/day) within 30 days of study entrance or chronic systemic steroid use.
- Evidence of progressive MS.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
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 17 Dec 2019.
- Background: PubMed 2082944Wynn DR, Rodriguez M, O'Fallon WM, Kurland LT. A reappraisal of the epidemiology of multiple sclerosis in Olmsted County, Minnesota. Neurology. 1990 May;40(5):780-6. doi: 10.1212/wnl.40.5.780.
- Background: PubMed 11006371Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med. 2000 Sep 28;343(13):938-52. doi: 10.1056/NEJM200009283431307. No abstract available.
- Background: PubMed 8780061Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology. 1996 Apr;46(4):907-11. doi: 10.1212/wnl.46.4.907.
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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.
Steven Jacobson, Ph.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
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 Multiple Sclerosis, run by National Institute of Neurological Disorders and Stroke (NINDS) 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 7 inclusion and 28 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 17 Dec 2019. 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00325988, which also lists 3 linked publications.
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 17 Dec 2019.