Motor Neurone Disease - Systematic Multi-Arm Adaptive Randomised Trial

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.

Conditions

• Motor Neuron Disease, Amyotrophic Lateral Sclerosis

Interventions

DRUG

Memantine Hydrochloride Oral Solution

Memantine hydrocholoride taken once daily

DRUG

Trazodone Hydrochloride oral solution

Trazodone Hydrochloride taken once daily

DRUG

Placebo oral solution

Placebo taken once daily

DRUG

Amantadine Hydrochloride Oral Solution

Amantadine Hydrochloride taken once daily

DRUG

Tacrolimus 1Mg Cap

Tacrolimus 1Mg overencapsulated tablet taken once daily

DRUG

Placebo capsule

Placebo taken once daily

Sponsors & Collaborators

• University College, London

  collaborator OTHER

• University of Warwick

  collaborator OTHER

• NHS Lothian

  collaborator OTHER_GOV

• University of Edinburgh

  lead OTHER

Principal Investigators

• Professor Chandran · University of Edinburgh

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-02-27

Primary Completion

2030-12-31

Completion

2030-12-31

Countries

• United Kingdom

Study Locations