Double Blind Placebo Controlled Pilot Trial of Memantine for Cognitive Impairment in Multiple Sclerosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 82
- 试验地点
- 4
- 主要终点
- Change in the Paced Auditory Serial Addition Test and the California Verbal Learning Test II (multivariate end-point) after 15 weeks of treatment.
研究概览
简要总结
This study is designed to determine whether memantine is an effective treatment for memory and cognitive problems associated with multiple sclerosis when compared to placebo.
详细描述
Objective:
The objective of this pilot project is to conduct a clinical trial to assess the efficacy of memantine as a treatment for cognitive dysfunction in multiple sclerosis (MS). We hypothesize that MS patients with cognitive impairment treated with memantine will demonstrate an improvement in performance on a neuropsychological test battery as compared to placebo treated patients.
Background and Significance:
Cognitive dysfunction is a major cause of disability in multiple sclerosis (MS). The estimated prevalence of cognitive dysfunction in the MS population is 45% to 65%. MS patients with cognitive dysfunction have fewer social interactions, more sexual dysfunction, greater difficulty with household tasks and higher unemployment than those with normal cognition. At present, there is no effective pharmacological symptomatic treatment for the cognitive dysfunction of MS. One agent that may have some benefit in treating this condition is the N-methyl-D-aspartate (NMDA) receptor antagonist memantine.
Memantine is a NMDA antagonist that has been shown to be effective in treating Alzheimer's disease. Glutamate toxicity has been implicated in the pathogenesis of a variety of neurologic diseases, including MS. Glutamate receptor activation may be involved both in mediation of neural injury and in neuronal dysfunction. By blocking NMDA receptors, memantine may both improve neuronal function, explaining symptomatic improvement in some Alzheimer's patients, and slow progressive neuronal death, potentially resulting in a slowing of cognitive decline in Alzheimer's patients. The pathogenesis of cognitive dysfunction in MS relates at least in part to the extent of cerebral demyelination, axonal loss and atrophy. Some cognitive dysfunction is reversible. Reduction in inflammation can result in improvement in cognitive performance. What role NMDA receptors and glutamate toxicity may play in cognitive dysfunction is uncertain but, given the lack of any treatment for cognitive dysfunction in MS, performing a pilot trial of memantine in MS is clearly warranted.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double
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
- •A diagnosis of multiple sclerosis as defined by the McDonald criteria. Patients with relapsing-remitting, secondary progressive, and primary progressive forms of MS are eligible.
- •Age between 18 and 65 years.
- •Demonstrated cognitive dysfunction at screening defined as a score worse than 1.0 standard deviations below the mean on the PASAT or the CVLT-II.
排除标准
- •A history of major depression, psychosis, or a score > 19 on the Beck's Depression Inventory.
- •Corrected binocular visual acuity worse than 20/50; any impairment of binocular color vision.
- •Patients that do not speak English as a primary language (fluency may impact performance).
- •A clinically significant MS exacerbation within 30 days of the screening
- •Renal insufficiency.
- •History of seizures.
- •Patients using acetazolamide (Diamox, Ak-sol, Storzolamide), dichlorphenamide (Daranide), methazolamide (Neptazane) or topiramate (Topamax), dextromethorphan (Robitussin DM and other cold remedies), or amantadine (Symmetrel).
- •Use of medical marijuana in the prior six months.
- •History of alcohol abuse or illicit drug use in the prior six months.
结局指标
主要结局
Change in the Paced Auditory Serial Addition Test and the California Verbal Learning Test II (multivariate end-point) after 15 weeks of treatment.
次要结局
- Symbol Digit Modalities Test
- Modified Fatigue Impact Scale
- Controlled Oral Word Association Test
- Stroop Color and Word Test
- Perceived Deficit Questionnaire
- Delis-Kaplan Executive Function System
- Beck Depression Inventory
- Multiple Sclerosis Screening Neuropsychological Questionnaire
- Modified Neuropsychiatric Inventory
- MS Quality of Life Inventory
- Fatigue Severity Scale