Motor Neurone Disease - Systematic Multi-Arm Adaptive Randomised Trial
概览
- 阶段
- 2 期
- 干预措施
- Memantine Hydrochloride Oral Solution
- 疾病 / 适应症
- Motor Neuron Disease, Amyotrophic Lateral Sclerosis
- 发起方
- University of Edinburgh
- 入组人数
- 1150
- 试验地点
- 22
- 主要终点
- Change in decline of ALS-FRS(R) over 18months
- 状态
- 招募中
- 最后更新
- 上个月
概览
简要总结
MND-SMART is investigating whether selected drugs can slow down the progression of motor neuron disease (MND) and improve survival.
The study is 'multi-arm' meaning more than one treatment will be tested at the same time. The trial started with 3 arms; drug 1 (memantine), drug 2 (trazodone) and placebo (dummy drug). A third drug, amantadine, was added in April 2023. A fourth drug, tacrolimus, was added in March 2025 in Edinburgh and across all sites in April 2025. The first two drugs, memantine and trazodone, were removed from the trial in September 2023 due to lack of benefit. The trial currently has 4 recruiting arms; amantadine, liquid placebo (matched to amantadine), tacrolimus, and tablet placebo (matched to tacrolimus). This allows the evaluation of each drug versus placebo. Participants will be randomly allocated between the treatment arms they are eligible for. Medicines being tested are already approved for use in other conditions.
MND-SMART has an 'adaptive' design. This means medicines being studied can change according to emerging results. Treatments shown to be ineffective can be dropped and new drugs can be added over the duration of the study. This will allow many treatments, over time, to be efficiently and definitively evaluated.
The medicines being tested have been selected following a rigorous process involving a systematic, unbiased, and comprehensive review of past clinical trials data, as well as information from pre-clinical research (studies in laboratories), for MND and other related neurodegenerative disorders. Drugs have been ranked for inclusion in MND-SMART by a group of independent MND experts according to set criteria. These include consideration of how the drugs work, their safety profiles, and the quality of previous studies.
New drugs will be selected for investigation in MND-SMART based on continuous review of constantly updated scientific evidence as well as findings from state-of-the-art human stem cell based drug discovery platforms. These can be added by substantial amendment to the protocol.
详细描述
For further information, please visit: https://mnd-smart.org/
研究者
入排标准
入选标准
- •Participants will be considered eligible for randomisation if they fulfil all the core inclusion criteria and none of the
排除标准
- •as defined below. In addition, investigators must simultaneously check and ensure participants do not meet any of the drug specific exclusion criteria. If exclusion criteria are met for an arm, participants can still be considered for other arms and randomised accordingly to eligible arms.
- •Core inclusion criteria:
- •Confirmed diagnosis of MND. This includes the following subtypes: ALS by El Escorial Criteria (possible, probable, and definite) or Gold Coast Criteria, Primary Lateral Sclerosis, and Progressive Muscular Atrophy
- •Women of childbearing potential according to CTFG guidelines must have a negative pregnancy test within 7 days prior to, or at, the baseline visit
- •Women of childbearing potential and fertile men must be using an appropriate method of contraception to avoid any unlikely teratogenic effects of the selected drugs from time of consent, to 4 weeks after treatment inclusive
- •Willing and able to comply with the trial protocol and ability to understand and complete questionnaires
- •Written informed consent (in the case of limb dysfunction verbal consent can be given in the presence of a witness who can sign)
- •Core Exclusion Criteria:
- •Patients diagnosed with Frontotemporal Dementia (FTD-MND) or any other significant psychiatric disorder that prevents informed consent being given.
- •Alcoholism (current self-reported - at the investigator's discretion)
研究组 & 干预措施
Memantine
干预措施: Memantine Hydrochloride Oral Solution
Trazodone
干预措施: Trazodone Hydrochloride oral solution
Placebo (liquid)
干预措施: Placebo oral solution
Amantadine
干预措施: Amantadine Hydrochloride Oral Solution
Tacrolimus
干预措施: Tacrolimus 1Mg Cap
Placebo (tablet)
干预措施: Placebo capsule
结局指标
主要结局
Change in decline of ALS-FRS(R) over 18months
时间窗: 18 months
Co-primary outcome measure
Survival
时间窗: 18 months
Co-primary outcome measure
次要结局
- Cognition and behaviour(18 months)
- Respiratory function - Forced vital capacity(18 months)
- King's ALS Clinical stage(18 months)
- Changes in anxiety and depression(18 months)
- Changes in Quality of Life(18 months)
- Safety and tolerability of IMPs(18 months)