Clinical Trial Ceftriaxone in Subjects With Amyotrophic Lateral Sclerosis (ALS)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 513
- 试验地点
- 58
- 主要终点
- Survival
研究概览
简要总结
The purpose of the study is to evaluate the safety and efficacy of ceftriaxone treatment in amyotrophic lateral sclerosis (ALS).
详细描述
It is known that nerve cells called motor neurons die in the brains and spinal cords of people with amyotrophic lateral sclerosis (ALS). However, the cause of this cell death is unknown. Researchers think that increased levels of a chemical called "glutamate" may be related to the cell death. For this reason researchers want to study drugs that decrease glutamate levels near nerves. Ceftriaxone-a semi-synthetic, third generation cephalosporin antibiotic-may increase the level of a protein that decreases glutamate levels near nerves. Studies of ceftriaxone in the laboratory suggest that it may protect motor neurons from injury.
Ceftriaxone is approved by the U.S. Food and Drug Administration (FDA) for treating bacterial infections but not for treating ALS. Also, ceftriaxone has not been given to people over a long period of time, such as months or years. The goals of this study are to evaluate the safety and effectiveness of ceftriaxone as a treatment for ALS, and to determine the safety and effectiveness of long-term use of the drug in people with ALS.
A total of 600 eligible people with ALS will be enrolled in this multi-center research study. Participants will be randomly assigned to receive treatment with ceftriaxone (2/3 of participants) or placebo (1/3 of participants) for at least 12 months.
The study consists of three stages. The first stage, which has completed enrollment, will look at whether ceftriaxone enters the cerebrospinal fluid (the fluid that surrounds the spinal cord, also called CSF) in amounts that are high enough to be of possible benefit. The second stage, which has also completed enrollment, will look at the safety and side effects of the study drug when taken daily for at least 20 weeks. The study is currently enrolling subjects for the third stage, which began in Spring 2009, and will determine whether the study drug prolongs survival and slows decline in function due to ALS.
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 (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants will be people with ALS, at least 18 years of age.
- •Participants must be medically able to undergo the study procedures and have a caregiver or other individual who will be available to help with daily study medication administration.
- •Participants should live within a reasonable distance of the study site, due to frequent study visits.
排除标准
- •Participants cannot be taking any other experimental medications for ALS, or have a history of sensitivity to cephalosporin antibiotics (such as Ancef, Keflex, Ceclor, Ceftin, Lorabid, Suprax, or Fortaz).
研究组 & 干预措施
Ceftriaxone
Two thirds of participants were assigned to 4 grams of ceftriaxone per day. This is a blinded study, so neither participants nor study staff will know which treatment a participant is receiving.
Ceftriaxone is a cephalosporin antibiotic and was administered intravenously via a central venous catheter twice a day.
干预措施: ceftriaxone (Drug)
Placebo
One third of participants were assigned to placebo, or an inactive substance. This is a blinded study, so neither participants nor study staff will know which treatment a participant is receiving.
Pediatric multivitamin solution was used as the placebo in this study and was administered intravenously via a central venous catheter twice a day.
干预措施: placebo (Other)
结局指标
主要结局
Survival
时间窗: From date of randomization until date of death, tracheostomy, or the initiation of permanent assisted ventilation (PAV). This was assessed at time of each participant's drug discontinuation and every 2 months thereafter for the life of the study (6 yrs)
Survival is presented as median day of survival for each group. Survival is defined as time to death, tracheostomy or the initiation of permanent assisted ventilation (PAV).
Change From Baseline in ALS Functional Rating Scale, Revised (ALSFRS-R) at One Year
时间窗: Every 8 weeks for one year
Amyotrophic Lateral Sclerosis Functional Rating Scale, Revised (ALSFRS-R) is a quickly administered (five minute) ordinal rating scale used to determine patients' assessment of their capability and independence in 12 functional activities/questions. The 12 functional activities/questions are rated on a scale of 0 to 4 for a total scoring range of 0-48, with 48 representing optimal function. All 12 activities are relevant in ALS. This outcome measure calculation is based on measurements every 8 weeks from the Baseline Visit up until one year.
次要结局
- Change From Baseline in the ALS-Specific Quality of Life Scale (ALSQOL) at One Year(Every 12 weeks for one Year)
- Change in % Vital Capacity From Screening to One Year(Every 12 weeks for one Year)
- Change From Baseline in Evaluation of Multiple Lower Extremity Muscles Using Hand Held Dynamometry at One Year(Every 12 weeks for one Year)
- Change From Baseline in Evaluation of Multiple Upper Extremity Muscles Using Hand Held Dynamometry at One Year(Every 12 weeks for one Year)
研究者
Merit E. Cudkowicz, MD
Professor of Neurology
Massachusetts General Hospital