Metformin as an add-on or Monotherapy in Treatment of Aging People With Multiple Sclerosis (MS): Randomized, Placebo-controlled Pilot Study.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
研究概览
简要总结
The goal of the study is to learn about treating older people with multiple sclerosis (MS) with metformin. Metformin may be used as a single therapy or as an add-on therapy. The investigators want to learn:
- The safety and tolerability of metformin extended release (1500 mg/day) as a single therapy or as an add-on therapy in older people with MS compared to placebo
- How well metformin protects the nervous system against injury compared with placebo measured by brain MRI over a 9 month treatment period
- The effect of metformin to protect brain tissue from age and MS related injury when compared to the placebo group over a 9 month treatment period
详细描述
Specific aims and rationale:
The main aim of this study is to determine the safety of metformin as monotherapy or as an add-on therapy to the disease modifying treatment in aging people with multiple sclerosis (pwMS). While the tolerability of metformin has been studies in the general population, data specific to the MS population is not currently available. Moreover, understanding the gastrointestinal tolerability of metformin when added on MS disease modifying treatment is needed. Secondly, the study aims at understating the potential neuroprotective properties of metformin as measured through magnetic resonance spectroscopy and change in N-acetyl-aspartate (NAA) levels over a 9-month study period. This pilot study will provide valuable insights into the efficacy and safety of add-on or monotherapy metformin therapy as a potential therapeutic approach to address the complex pathophysiology of MS and offer new avenues for promoting neuroprotection along with potential support for neural repair and remyelination in individuals with this debilitating condition. Previous pre-clinical studies have shown that metformin can promote neuroprotection by reducing oxidative stress and inflammation and is able to enhance the reparative mechanisms within the central nervous system (CNS). Currently there are no neuroprotective interventions available for pwMS that directly target the neurodegenerative component of MS, with particular emphasis for the aging MS population. The investigators hypothesize that older pwMS that are treated with metformin will have a significantly lower decline in N-acetylaspartate levels when compared to pwMS not treated with metformin.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 55 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age between 55 and 75 years old
- •having a diagnosis of MS based on the latest McDonald criteria
- •non-active disease course (no relapses and no MRI activity) in the last 2 years as determined by the MS provider and based on the 2020 revised clinical course criteria
- •EDSS score <7.0
排除标准
- •inability to undergo MRI scans
- •inability to participate in the study during the study period
- •diabetes or uncontrolled cardiovascular disease
- •unable to consent
研究组 & 干预措施
metformin
metformin
干预措施: metformin (Drug)
placebo
placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
时间窗: 1 year
The adverse events (AE) will be collected using standardized Adverse Events Form. The severity of the AE will be determined using 5-level grading system where Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of daily living (ADL); Grade 3: Severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL; Grade 4: Life-threatening consequences; urgent intervention indicated; and Grade 5: Death related to AE. Additional information regarding the relation to the study medication (related/non related), treatment required (none/drug/non-drug) and the outcome of the AE will be recorded
Percent change in N-Acetyl Aspartate (NAA) in the cortex over 9 months
时间窗: 9 months
The MRI scans will be acquired at baseline and 9-month follow-up using magnetic resonance spectroscopy (MRS).
次要结局
- Brief Visuospatial Memory Test ( BVMT)(1 year)
- Conventional MRI outcomes(9 months)
- 9-hole peg test (9HPT)(1 year)
- Symbol Digit Modality Test (SDMT)(1 year)
- California Verbal Learning Test (CVLT)(1 year)
- Timed 25-foot walk test (T25FWT)(1 year)
- Disability progression as measured with Expanded Disability Status Scale (EDSS)(1 year)
- Myelin water fraction (MWF)(9 months)
研究者
Bianca Weinstock-Guttman
Professor of Neurology
State University of New York at Buffalo