Central and Peripheral Nervous System Changes as Markers of Disease Progression in Multiple Sclerosis
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 49
- 试验地点
- 1
- 主要终点
- Timed 25-Foot Walk Test (T25FW)
研究概览
简要总结
OBJECTIVE To investigate neurodegeneration and demyelination in the central and peripheral nervous system in multiple sclerosis linked to disease progression and mechanisms that can explain different responses to Fampridine treatment in MS patients with walking disability.
METHOD The study is a prospective cohort follow-up study with 98 participants with MS and walking disability. Participants are identified as responders or non-responders to Fampridine treatment prior to the study. Participants will undergo MRI of the cerebrum with lesion load quantification, neurophysiological tests comprised of motor evoked potentials and electroneurographic examination, blood samples examining KIR4.1 antibodies, brain derived neurotrophic factor (BDNF), myelin protein zero (MPZ), peripheral myelin protein 22 (PMP22), p75-nerve growth factor receptor (p75NGFR) and anti-myelin associated glycoprotein (anti-MAG). The presence of SORCS-3 gene mutation will also be examined, as will cerebrospinal fluid levels of myelin basic protein, neurofilament heavy and light chains. Functional test of Timed 25-foot walk test (T25FW) will identify response to Fampridine treatment. A functional test battery will further detail function of upper extremities and cognition.
CONCLUSION This study will add to the understanding of neurodegeneration and demyelination in CNS and PNS in patients with MS having walking disability. This will impact clinical decision-making by improving organization of immunomodulatory treatment, identifying biomarkers thus facilitating earlier treatment and improving patient control, information and education.
详细描述
BACKGROUND Multiple Sclerosis (MS) is an autoimmune, inflammatory demyelinating disease targeting myelinated axons in the Central Nervous System (CNS). It is the most common nontraumatic cause of disability in young people. Most MS patients are diagnosed between the ages of 20 and 40 years. Denmark has a prevalence of approximately 155 MS patients per 100,000 inhabitants, which is among the highest in the world. The etiology of MS is not known, however, a combination of genetic and environmental factors is likely to be involved in triggering the disease.
CLINICAL PRESENTATION MS damages the CNS and causes progressive disability. Clinical symptoms of the patient depend on the location of the lesions that can occur anywhere in the CNS. Consequently the neurological impairments are very variable and consist of sensory, motor, visual, urinary, coordination and cognitive deficits. MS is divided into several categories based on disease progression: relapse-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS) and primary progressive multiple sclerosis (PPMS). Clinically isolated syndrome (CIS) is a single relapse compatible with MS accompanied by paraclinical evidence of demyelination with more than 80 percent of patients with CIS developing MS at a later stage.
WORKUP
McDonald criteria are used for diagnosing MS. They are based on clinical findings supported by paraclinical tests mentioned below. The aim is to demonstrate neurological impairments disseminated in time (lesions in the CNS are of different age) and localization in the CNS, while excluding other conditions:
- Magnetic Resonance Imaging (MRI) of the brain and spinal cord is used to demonstrate lesions in the CNS.
- Lumbar puncture is performed in order to demonstrate inflammation in the CNS. Analysis of the CSF can also exclude infection in the CNS.
- Blood Samples are drawn to assess IgG, glucose and albumin in order to assess levels on both sides of the blood brain barrier (BBB) and to exclude other conditions.
- Evoked Potentials are useful at identifying subclinical lesions.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants are diagnosed with MS according to the McDonald criteria.
- •Categorized as responder or non-responder to Fampridine treatment.
- •Age in the range of 18-65 years.
- •Extended Disability Status Scale (EDSS) 4-7 points.
- •Pyramidal Functions Score ≥ 2 in the Kurtzke Functional Systems Scores (FSS).
排除标准
- •MS-attack and/or change in immunomodulatory treatment within 60 days before inclusion.
- •Simultaneous use of medications that inhibit the organic cation transporter (OCT2).
- •History of epileptic seizures.
- •Clinically manifest heart-, liver-, kidney- (glomerular filtration rate < 80 ml/min), pulmonary disease, diabetes, alcohol intake exceeding the National Institute of Health's recommendations and pregnancy.
结局指标
主要结局
Timed 25-Foot Walk Test (T25FW)
时间窗: Baseline up to 6, 12 and 18 months.
The patient walks 25 feet as fast as possible. The test is repeated twice and the mean is used as the test result. This functional test measures walking speed and acceleration. This functional test has a high inter-rater and test-retest reliability and shows evidence of good concurrent validity. Hobart et al. have estimated the MCID for T25FW as an improvement \>20% and Jensen et al. have recently estimated it to 17.8% when based on data distribution approach.
次要结局
- Twelve Item MS Walking Scale (MSWS-12)(Baseline up to 6, 12 and 18 months.)
- 5-Times-Sit-to-Stand Test (5-STS)(Baseline up to 6, 12 and 18 months.)
- 9-Hole Peg Test (9-HPT)(Baseline up to 6, 12 and 18 months.)
- Guys Neurological Disability Scale (GNDS)(Baseline up to 6, 12 and 18 months.)
- The Six Spot Step Test (SSST)(Baseline up to 6, 12 and 18 months.)
- Antibodies(Baseline up to 12 months.)
- Symbol Digit Modalities Test (SDMT)(Baseline up to 6, 12 and 18 months.)
- MRI of the brain(Baseline up to 12 months.)
- Neurophysiologic examinations(Baseline up to 12 months.)
研究者
Sepehr Mamoei
M.D., Ph.D.-Fellow
University of Southern Denmark