A Pilot Trial to Investigate the Safety and Efficacy of Intestinal Microbiome Transplant (MTT) in People With Amyotrophic Lateral Sclerosis
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- ALS Quality of Life (ALSAQ-5)
研究概览
简要总结
This is a 24-week study of intestinal microbiome transplant in people with ALS. All participants will be evaluated clinically in person for 4 visits. Blood and mailed/ fresh stool samples will also be collected. Blood samples will be used to determine changes in neurofilament light chain over time. Stool samples will be processed for microbiome analysis. Participants will have phone visits to further evaluate safety and tolerability. They will then undergo antibiotic conditioning and a standard bowel preparation before being assigned to the investigational product, MTP-101C .
详细描述
This is a 24-week Phase I/II study of MTT in people with Amyotrophic Lateral Sclerosis. All participants will be evaluated clinically in person at weeks 0, 4, 12, and 24 visits. Blood and mailed/ fresh stool samples will be collected at weeks 0, 4, 8, 12, and 24. Blood samples will be used to determine changes in neurofilament light chain over time. Stool samples from weeks 0, 4,8, 12, and 24 will be processed by molecular methods (metagenomics and metatranscriptomics) for microbiome analysis. Participants will also have phone visits at weeks 1, 8, 16, and 20, which will be used to further evaluate safety and tolerability and the ALSFRS-R score.
Participants will first undergo antibiotic conditioning with oral vancomycin 250 mg twice daily for 10 days. Neomycin 500 mg twice daily will be added to the last 3 days of vancomycin. This will be followed by ingestion of a standard bowel preparation with magnesium citrate. Participants will then ingest 2 capsules of MTP-101C daily for 3 days, then 1 capsule of MTP-101C daily for 8 weeks.
All participants will be assigned to the investigational product.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Diagnosis of ALS according to Gold Coast Criteria
- •Age: 18+ years at enrollment
- •Fast-progressing (ALSFRS-R change of at least 1.5 points per month between last 2 measurements at screening)
- •Modestly but not severely affected (ALSFRS-R score at or above 24 at screening)
- •Able to swallow capsules and expected to be able to for the duration of the trial (ALSFRS-R "swallowing" score of 3 or 4 at screening)
- •Expected to survive for the duration of the trial
- •Taking any combination of riluzole, edaravone, and/or tofersen at a stable dose for 30 days prior to screening, or not taking any of these and not expected to during the study.
- •Capable of giving written consent.
- •If sexually active, must agree to use contraceptive or abstinence for duration of treatment.
- •Females of child-bearing age must have negative pregnancy test at screening.
排除标准
- •Concurrent illness or laboratory abnormalities that could confound the measurement of ALS progression or the microbiome or interfere with the ability to complete the study.
- •Taking probiotics, nutraceuticals, or herbal remedies within 2 weeks of screening
- •Taking antibiotics within 3 months of screening.
- •Taking any investigational study drug within 30 days of screening or five half-lives of the prior agent.
- •Previous exposure to MTT.
- •Pregnancy.
- •Known specific food allergy with anaphylaxis
- •Other co-morbid conditions that, in the opinion of the study investigator, place the participant at increased risk of complications, interfere with study participation or compliance, or confound study objectives.
研究组 & 干预措施
MTP-101C administration
MTP-101C is a freeze-dried encapsulated universal donor microbiome-based formulation. Participants will ingest 2 capsules daily for 3 days then 1 capsule daily. This is preceded by antibiotic conditioning with a combination of vancomycin and neomycin, followed by a bowel purgative with magnesium citrate depending upon underlying comorbidities.
干预措施: MTP-101C (Drug)
结局指标
主要结局
ALS Quality of Life (ALSAQ-5)
时间窗: Weeks 0, 4, 12, and 24
The overall ALSAQ-5 score ranges from 0 (best imaginable health state) to 100 (worst imaginable health state).
ALS Functional Rating Scale, Revised (ALSFRS-R)
时间窗: Weeks 0, 4, 8, 12, 16, 20 and 24
The ALSFRS-R is a quickly administered (five minute) ordinal rating scale (ratings 0-4) used to determine patients' assessments of their capability and independence in 12 functional activities. The total score ranges from 0 to 48, where higher scores indicate better function.
Neurofilament Light Chain levels
时间窗: Weeks 0, 4, 12 and 24
Neurofilament light chain levels are elevated in the spinal fluid and the blood of patients with ALS and other neurodegenerative diseases, and higher levels predict more severe disease progression.
The Gastrointestinal Symptom Rating Scale (GSRS)
时间窗: Weeks 0, 4, 12, and 24
The Gastrointestinal Symptom Rating Scale (GSRS) is a 15-item questionnaire that can be used weekly to assess the severity of gastrointestinal symptoms experienced over the past week. The GSRS is designed to evaluate symptoms associated with common gastrointestinal disorders, such as reflux, abdominal pain, indigestion, diarrhea, and constipation. The questionnaire uses a seven-point Likert-type scale, with 1 representing no symptoms and 7 representing very troublesome symptoms. Higher scores on the subscales indicate more discomfort.
次要结局
- Microbiome composition(Screening/Baseline, Week 4, Week 12, and Week 24)