Motor Neurone Disease - Systematic Multi-Arm Adaptive Randomised Trial
MND-SMART
1 other identifier
interventional
1,150
1 country
22
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Feb 2020
Longer than P75 for phase_2
22 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 27, 2020
CompletedFirst Submitted
Initial submission to the registry
March 4, 2020
CompletedFirst Posted
Study publicly available on registry
March 10, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2030
March 4, 2026
March 1, 2026
10.8 years
March 4, 2020
March 2, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Change in decline of ALS-FRS(R) over 18months
Co-primary outcome measure
18 months
Survival
Co-primary outcome measure
18 months
Secondary Outcomes (6)
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
- +1 more secondary outcomes
Study Arms (6)
Memantine
EXPERIMENTALTrazodone
EXPERIMENTALPlacebo (liquid)
PLACEBO COMPARATORAmantadine
EXPERIMENTALTacrolimus
EXPERIMENTALPlacebo (tablet)
PLACEBO COMPARATORInterventions
Eligibility Criteria
You may not qualify if:
- 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)
- 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)
- Active suicide ideation assessed using the Columbia-Suicide Severity Rating Scale
- On concurrent investigational devices and medication (including biological therapy)
- Pregnancy or breast-feeding females
- If ALT, ALP, bilirubin or GGT \>3 times the upper limit of normal.
- If creatinine clearance (creatinine clearance or eGFR) \<35 ml/min.
- If TSH \<0.2mU/l (if possible to test free T4, then Serum free T4 \>25pmol/l)
- If corrected QT interval on 12 lead ECG \>500 ms
- +21 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University College, Londoncollaborator
- University of Warwickcollaborator
- NHS Lothiancollaborator
- University of Edinburghlead
Study Sites (22)
Southern Health and Social Care Trust, Craigavon Area Hospital
Portadown, County Armagh, BT63 5QQ, United Kingdom
Aberdeen Royal Infirmary
Aberdeen, United Kingdom
University Hospitals of Birmingham NHS Foundation Trust
Birmingham, B15 2TH, United Kingdom
University Hospitals Sussex NHS Foundation Trust
Brighton, United Kingdom
West Suffolk NHS Foundation Trust
Bury St Edmunds, IP33 2QZ, United Kingdom
Cambridge University Hospitals NHS Foundation Trust
Cambridge, CB2 0QQ, United Kingdom
Cardiff and Vale University Local Health Board
Cardiff, CF14 4XW, United Kingdom
Clinical Research Centre , Ninewells Hospital
Dundee, United Kingdom
Anne Rowling Regenerative Neurology Clinic
Edinburgh, EH16 4SB, United Kingdom
Royal Devon and Exeter Hospital
Exeter, United Kingdom
Queen Elizabeth University Hospital Clinical Research Facility
Glasgow, United Kingdom
NHS Highland Clinical Research Facility, Raigmore Hospital
Inverness, United Kingdom
East Suffolk and North Essex NHS Foundation Trust
Ipswich, CO4 5JL, United Kingdom
Royal London Hospital
London, E1 1FR, United Kingdom
St George's University Hospitals NHS Foundation Trust
London, SW17 0QT, United Kingdom
King's College Hospital NHS Foundation Trust
London, United Kingdom
Newcastle upon Tyne Hospitals NHS Foundation Trust
Newcastle upon Tyne, NE7 7DN, United Kingdom
Norfolk and Norwich University Hospitals NHS Foundation Trust
Norwich, NR4 7UY, United Kingdom
University Hospitals of Dorset NHS Trust
Poole, United Kingdom
Clinical Research Facility Salford Royal NHS Foundation Trust
Salford, United Kingdom
Sheffield Teaching Hospitals NHS Foundation Trust
Sheffield, United Kingdom
Clinical Research Facility University Hospital Southampton
Southampton, United Kingdom
Related Publications (4)
Pal S, Chataway J, Swingler R, Macleod MR, Carragher NO, Hardingham G, Selvaraj BT, Smith C, Wong C, Newton J, Lyle D, Stenson A, Dakin RS, Ihenacho A, Colville S, Mehta AR, Stallard N, Carpenter JR, Parker RA, Keerie C, Weir CJ, Virgo B, Morris S, Waters N, Gray B, MacDonald D, MacDonald E, Parmar MKB, Chandran S; MND SMART Investigators. Safety and efficacy of memantine and trazodone versus placebo for motor neuron disease (MND SMART): stage two interim analysis from the first cycle of a phase 3, multiarm, multistage, randomised, adaptive platform trial. Lancet Neurol. 2024 Nov;23(11):1097-1107. doi: 10.1016/S1474-4422(24)00326-0. Epub 2024 Sep 19.
PMID: 39307154DERIVEDWong C, Gregory JM, Liao J, Egan K, Vesterinen HM, Ahmad Khan A, Anwar M, Beagan C, Brown FS, Cafferkey J, Cardinali A, Chiam JY, Chiang C, Collins V, Dormido J, Elliott E, Foley P, Foo YC, Fulton-Humble L, Gane AB, Glasmacher SA, Heffernan A, Jayaprakash K, Jayasuriya N, Kaddouri A, Kiernan J, Langlands G, Leighton D, Liu J, Lyon J, Mehta AR, Meng A, Nguyen V, Park NH, Quigley S, Rashid Y, Salzinger A, Shiell B, Singh A, Soane T, Thompson A, Tomala O, Waldron FM, Selvaraj BT, Chataway J, Swingler R, Connick P, Pal S, Chandran S, Macleod M. Systematic, comprehensive, evidence-based approach to identify neuroprotective interventions for motor neuron disease: using systematic reviews to inform expert consensus. BMJ Open. 2023 Feb 1;13(2):e064169. doi: 10.1136/bmjopen-2022-064169.
PMID: 36725099DERIVEDParker RA, Weir CJ, Pham TM, White IR, Stallard N, Parmar MKB, Swingler RJ, Dakin RS, Pal S, Chandran S. Statistical analysis plan for the motor neuron disease systematic multi-arm adaptive randomised trial (MND-SMART). Trials. 2023 Jan 16;24(1):29. doi: 10.1186/s13063-022-07007-z.
PMID: 36647114DERIVEDWong C, Dakin RS, Williamson J, Newton J, Steven M, Colville S, Stavrou M, Gregory JM, Elliott E, Mehta AR, Chataway J, Swingler RJ, Parker RA, Weir CJ, Stallard N, Parmar MKB, Macleod MR, Pal S, Chandran S. Motor Neuron Disease Systematic Multi-Arm Adaptive Randomised Trial (MND-SMART): a multi-arm, multi-stage, adaptive, platform, phase III randomised, double-blind, placebo-controlled trial of repurposed drugs in motor neuron disease. BMJ Open. 2022 Jul 7;12(7):e064173. doi: 10.1136/bmjopen-2022-064173.
PMID: 35798516DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Professor Chandran
University of Edinburgh
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 4, 2020
First Posted
March 10, 2020
Study Start
February 27, 2020
Primary Completion (Estimated)
December 1, 2030
Study Completion (Estimated)
December 1, 2030
Last Updated
March 4, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
- Time Frame
- After publication of study results, no end date.
- Access Criteria
- Data will be shared with researchers who provide a methodologically sound proposal to achieve the aims of the proposal only. Data sharing request forms are available from mnd-smart@Ed.ac.uk. Requesters will need to sign a data access agreement prior to being provided with access to data.
To ensure data transparency, the results of any closed comparisons will be published in a peer reviewed journal as soon as it is possible when the integrity of the trial will not be affected. Individual level participant data will be shared ,after deidentification, upon receipt of a valid request. Some data may be shared prior to the publication of study results depending on the requirements, however no end point data will be released without explicit need and permission from the TSC. Each data request form will be individually reviewed to ensure the proposal has a valid rationale and appropriate methodology. Only data required for the project will be shared. A summary of results will be provided to all participants via newsletters and the trial website.