RecruitingPhase 2/3

Motor Neurone Disease - Systematic Multi-Arm Adaptive Randomised Trial

United Kingdom1,150 participantsStarted 2020-02-27

Plain-language summary

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.

Who can participate

Age range

18 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Participants will be considered eligible for randomisation if they fulfil all the core inclusion criteria and none of the exclusion criteria 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 * Over 18 * 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…

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Change in decline of ALS-FRS(R) over 18months

Timeframe: 18 months

Survival

Timeframe: 18 months

Trial details

NCT IDNCT04302870

SponsorUniversity of Edinburgh

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2030-12

Contact for this trial

Professor Chandran

0131 465 9612 siddharthan.chandran@ed.ac.uk

View on ClinicalTrials.gov More Motor Neuron Disease, Amyotrophic Lateral Sclerosis trials