What is MND SMART?

MND SMART (Motor Neurone Disease - Systematic Multi-Arm Adaptive Randomised Trial) is 'multi-arm' meaning more than one treatment will be tested at the same time.The trial will initially test medicines that are already approved as treatments for other disorders in the UK. Trial participants taking the different treatments will be compared with a single group who receive a placebo (a dummy drug). This means that people in MND-SMART are more likely to receive an active treatment when compared to standard clinical trials where half of participants receive the placebo and half the active treatment.

The trial started out with 3 arms; drug 1 (Memantine Hydrochloride - phase 2), drug 2 (Trazodone Hydrochloride - phase 3) and placebo (dummy drug). This allows the evaluation of drug 1 versus placebo and separately drug 2 versus placebo. Participants will be randomly allocated to either drug 1, drug 2 or placebo. Medicines being tested are already approved for use in other conditions. Currently recruiting in trial centres across the UK.

A new drug, called Amantadine Hydrochloride, was added to the trial in April 2023. In September 2023, Memantine and Trazodone were removed from the trial due to lack of benefit. A further 3 drugs are expected to be added to the trial in 2024/2025.

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. You can find out more about the trial here

What do the drugs do?

Memantine hydrochloride

Memantine hydrochloride is a drug which is already used to treat Alzheimer’s disease. It works by reducing the action of glutamate. Glutamate is a neurotransmitter, meaning it helps nerve cells to communicate. However, in MND it is thought that the over activity of glutamate can be toxic and cause cells to die.

Trazodone Hydrochloride

Trazodone Hydrochloride is a drug which is already used to treat anxiety and depression. It works by slowing the production of faulty proteins in nerve cells. The accumulation of these faulty proteins is though to cause cells to die in MND.

Amantadine Hydrochloride

Amantadine Hydrochloride is a drug which is already use in the management of Parkinson’s disease, treatment of fatigue in MS and as an antiviral medicine in the treatment of Type A influenza. It has a number of mechanisms of actions including boosting dopamine activity and reducing glutamate. In MND, it is thought that over activity of glutamate can be toxic and cause cells to die. Dopamine is an important neurotransmitter involved in motor control and neuron signalling.

How can I take part in the trial?

Recruiting Sites

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

  • Edinburgh
  • Dundee
  • Glasgow
  • Salford
  • Aberdeen
  • Inverness
  • Southampton
  • Exeter
  • Norfolk
  • St George's London
  • West Suffolk
  • Birmingham
  • Ipswich
  • Newcastle
  • Cambridge
  • Barts/Royal London
  • Craigavon, Northern Ireland
  • Poole
  • Cardiff
  • Sheffield
  • Brighton
  • Kings College London

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

Trial Results

Memantine Hydrochloride

The memantine arm was ended early after the trail 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. 

Trazodone Hydrochloride

The trazodone arm was ended early after the trail 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. 

Latest News

2023

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.

2022

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.

Last updated: 28/09/2023