A Double-blind, Placebo Controlled Trial of Metformin Treatment in Progressive Multiple Sclerosis
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- number of patients with new T2 lesions on MRI from baseline to conclusion (month 0 and month 12)
研究概览
简要总结
The purpose of this study is to assess the safety of metformin for treatment of progressive multiple sclerosis
详细描述
This will be a single site 1:1 randomized, placebo controlled trial of metformin treatment vs matching placebo in 44 men and women with primary progressive multiple sclerosis and secondary multiple sclerosis, without diabetes, not treated with metformin aged 30-65. The trial will last 12 months and have 3 study visits, baseline, 6 months, and 12 months. The trial will be preceded by a screening period. Over the initial 30 day titration period subjects will be titrated from 500 mg a day to 2,000 mg of metformin in increments of 500 mg every 10 days. Patients will remain on their tolerated dose and included in analysis on an intent to treat basis. Brain MRI, cognitive testing and clinical measures will be collected at baseline, month 6 and month 12. OCT will be collected at baseline and month 12. The primary outcomes are the following safety outcomes: 1) number of patients with adverse events 2) number of patients with laboratory abnormalities 3) number of patients with new T2 lesions on MRI. The secondary outcomes include reduction in localized cortical thinning on brain MRI; reduction in thalamic atrophy on brain MRI. Further exploratory outcomes include 1) improvement in SDMT-oral score, 2) improvement in CVLT-II score, 3) improvement in PACC score 4) improvement in PASAT score. Exploratory outcomes include 1) Decrease in plasma neurofilament light chain levels, 2) Reginal nerve fiber layer preservation on OCT, 3) Ganglion cell inner plexiform layer preservation, and 4) Percentage of phase rim lesions.
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
- 30 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient signed informed consent.
- •Primary Progressive Multiple Sclerosis or Secondary Progressive Multiple Sclerosis as defined by the 2017 McDonald Criteria
- •Intent to maintain current MS disease modifying treatment through the trial duration
排除标准
- •Clinical relapse in prior 12 months
- •New T2 lesion or gadolinium enhancing lesion in prior 12 months
- •Glucocorticoid use in prior six months outside the context of premedication for disease modifying treatment
- •Changes in disease modifying therapy in prior three months
- •Plans to change current disease modifying therapy
- •Contraindication to MRI, inability to tolerate MRI
- •Use of metformin for any other indication
- •Renal dysfunction (GFR < 60)
- •Hepatic dysfunction (AST or ALT > 1.5 x upper limit of normal)
- •B12 deficiency
- •Prior poor reaction to metformin
- •Congestive heart failure
- •Alcohol abuse
- •Metabolic acidosis
- •Females who are pregnant or who plan to become pregnant during the 12 months of enrollment, or who wish to breastfeed during any part of the 12 months of enrollment
- •Concomitant use of drugs with drug-drug interactions with metformin
- •Previous adverse effect with metformin treatment
研究组 & 干预措施
Metformin Treatment
Metformin 500 mg tablets up to 2,000 mg (4 tablets) a day divided into two doses. Patients will start on 500 mg Qday and a titration to maximum dose will be attempted during the first 30 day period of the study.
干预措施: Metformin 500 Mg Oral Tablet, up to 4 tablets a day (Drug)
Placebo Treatment
Placebo tablets identical to metformin 500 mg tablets divided into two doses. Patients will be started on 1 tablet a day and a titration to maximum dose (4 tablets) will be attempted during the first 30 day period of the study.
干预措施: Placebo oral tablet identical to metformin, up to 4 tablets a day (Drug)
结局指标
主要结局
number of patients with new T2 lesions on MRI from baseline to conclusion (month 0 and month 12)
时间窗: between month 0 and month 12
number of patients with new T2 lesions comparing the two treatment groups
number of patients with adverse events between baseline and conclusion (month 0 and month 12)
时间窗: between month 0 and month 12
number of patients with adverse events comparing the two treatment groups
number of patients with laboratory abnormalities between baseline and conclusion (month 0 and month 12)
时间窗: between month 0 and month 12
number of patients with laboratory abnormalities comparing the two treatment groups
次要结局
- a reduction in localized cortical thinning on brain MRI between baseline and conclusion (month 0 and month 12)(between month 0 and month 12)
- a reduction in thalamic atrophy on brain MRI between baseline and conclusion (month 0 and month 12)(between month 0 and month 12)
研究者
Kevin Patel
Assistant Professor, Department of Neurology
University of California, Los Angeles