MND SMART

Current status: Open for recruitment

What is the drug thought to do in the body?

Tacrolimus is an existing drug which is used to treat some immune system disorders and prevent the body from rejecting organ transplants. It works by dampening down the activity of the immune system. It is thought that the immune system might become overactive in MND and that this may play a role in driving the progression of the disease. Laboratory studies into Tacrolimus in MND have suggested that it may be able to stop faulty proteins from forming clumps in cells and reduce inflammation in the central nervous system. 

The trial is currently recruiting in the UK at the following sites:

• Aberdeen
• Birmingham
• Brighton
• Bury St Edmunds, West Suffolk
• Cambridge
• Craigavon, Northern Ireland
• Dundee
• Edinburgh
• Exeter
• Glasgow
• Hull
• Inverness
• Ipswich
• Kings College London
• Newcastle
• Norwich/Norfolk
• Poole
• Royal London
• Salford
• Sheffield
• Southampton
• South Wales
• St George's London
• University College London
• York and Scarborough Hospitals

Find out more about recruiting sites and register your interest to take part here.

Phase: Phase 2/3 - this means that if the drugs appear to be effective, they will seamlessly transition into a phase 3 trial.

Placebo Controlled: Yes - this means that people joining the trial could be randomly assigned to receive the placebo (dummy drug). 

Open-Label Extension: No - this means that participants will only receive either the treatment or the placebo throughout the trial. However, if a drug is found to not be beneficial, participants may have the opportunity to re-enter the trial. However, participants will still be randomly assigned either the treatment or placebo. 

What is the drug thought to do in the body? 

In MND, a neurotransmitter called glutamate, which helps nerve cells communicate, has been shown to be over-active. This is thought to be toxic to nerve cells. Memantine aims to reduce the action of glutamate. 

Outcome

The memantine arm was ended early after the trial was evaluated as part of the regular interim analyses. At the stage 2 interim analysis, it was found that memantine was highly unlikely to be beneficial for people living with MND. This was shown by no significant improvement in the rate of change in the ALSFRS-R scale compared to the placebo – indicating no change in the rate of progression of the disease. 

What is the drug thought to do in the body? 

In MND, proteins (which are vital for all the tasks in a cell) have been shown become faulty and form toxic clumps. Trazadone aims to reduce the production of faulty proteins. 

Outcome

The trazodone arm was ended early after the trial was evaluated as part of the regular interim analyses. At the stage 2 interim analysis, it was found that trazodone was highly unlikely to be beneficial for people living with MND. This was shown by no significant improvement in the rate of change in the ALSFRS-R scale compared to the placebo – indicating no change in the rate of progression of the disease. 

What is the drug thought to do in the body?

In MND, it is thought that over activity of a chemical called glutamate can be toxic and cause cells to die. Dopamine is an important chemical involved in communication between neurons. Amantadine Hydrochloride is thought to boost dopamine activity and reduce glutamate activity. Amantadine is also thought to help reduce the abnormal clumping of the TDP-43 protein which occurs in around 97% of people with MND.

Outcome

The Amantadine arm was ended early after the trial was evaluated as part of the regular interim analyses. At the stage 2 interim analysis, it was found that Amantadine did not slow progression for people living with MND. This was shown by no significant improvement in the rate of change in the ALSFRS-R scale compared to the placebo – indicating no change in the rate of progression of the disease. 

March 2026 - The independent trial committee decided testing should not continue for Amantadine as it did not show benefit for people with MND.

June 2025  - A new drug was added to MND SMART, called Tacrolimus.

December 2024- The independent trial committee decided testing should continue for Amantadine Hydrochloride as no safety concerns were found.

September 2023 - The independent trial committee decided testing should not continue for trazadone and memantine as it was highly unlikely either drug would show people for people with MND. It was also announced that 3 new drugs will be added to the trial in 2024/2025.  

April 2023  - A new drug was added to MND SMART, called Amantadine Hydrochloride.

April 2022 - An independent review concluded that testing for both current drugs (Memantine and Trazodone) should be continued. Find out more. 

Jan 2022  - Over 260 participants have been recruited from 16 sites across the UK.

• Keeping MND-SMART moving

MND-SMART | Clinical trials for MND