Motor Neurone Disease - Systematic Multi-Arm Adaptive Randomised Trial
NCT ID: NCT04302870
Last Updated: 2025-06-12
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE2/PHASE3
1150 participants
INTERVENTIONAL
2020-02-27
2030-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
A Study to Assess FLX-787 in Subjects With Motor Neuron Disease Experiencing Muscle Cramps.
NCT03196375
Minocycline to Treat Amyotrophic Lateral Sclerosis
NCT00047723
A Study to Evaluate the Efficacy and Safety of Reldesemtiv in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT04944784
A Study to Assess the Pharmacodynamics of VK0214 in Male Subjects With AMN
NCT04973657
Efficacy and Safety Study of Aplindore in Patients With Restless Legs Syndrome
NCT00834327
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Memantine
Memantine Hydrochloride Oral Solution
Memantine hydrocholoride taken once daily
Trazodone
Trazodone Hydrochloride oral solution
Trazodone Hydrochloride taken once daily
Placebo (liquid)
Placebo oral solution
Placebo taken once daily
Amantadine
Amantadine Hydrochloride Oral Solution
Amantadine Hydrochloride taken once daily
Tacrolimus
Tacrolimus 1Mg Cap
Tacrolimus 1Mg overencapsulated tablet taken once daily
Placebo (tablet)
Placebo capsule
Placebo taken once daily
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Memantine Hydrochloride Oral Solution
Memantine hydrocholoride taken once daily
Trazodone Hydrochloride oral solution
Trazodone Hydrochloride taken once daily
Placebo oral solution
Placebo taken once daily
Amantadine Hydrochloride Oral Solution
Amantadine Hydrochloride taken once daily
Tacrolimus 1Mg Cap
Tacrolimus 1Mg overencapsulated tablet taken once daily
Placebo capsule
Placebo taken once daily
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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)
Exclusion Criteria
* 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
* Patient's diagnosed with ventricular arrhythmias, significant heart block (at the investigator's discretion)) or in the immediate recovery period after myocardial infarction (\< 6 weeks).
* Patients who the PI considers will not be able to comply with the study protocol.
* Patients in the manic phase of bipolar disorder.
* Patients with history of proven peptic ulcer confirmed on endoscopy
* Patients with active epilepsy
* Already taking the IMP in this comparison
* Known hypersensitivity, including hereditary fructose intolerance, or adverse reaction to the active substances and their excipients (as per SPCs for this comparison) or any past medical history contraindicating use of the IMP in this comparison
* Poorly controlled hypertension (Systolic BP\>180 mmHg or Diastolic BP\>100mmHg)
* Poorly controlled diabetes (HbA1c\>6.4% or 48mmol/mol)
* Hypertrophic cardiomyopathy or history of QT prolongation (including family history), congestive heart failure, bradyarrhythmias, and electrolyte abnormalities
* History of bleeding disorders or significant haematological or immune diseases including, congenital or acquired immune deficiency, anaemia (Hb\<130g/L for males and Hb\<120 g/L in females) and thrombocytopenia (platelet count \<150 × 109/L), use of other biological agents and immunosuppressant medications including oral/IV steroids
* Active or chronic infection (at PI discretion)
* History of Hepatitis B or C
* History of lymphoma and active malignancy
* Risk of dehydration due to reduced oral intake and lack of parenteral route
* Patient's contraindicated to tacrolimus according to SPC section 4.3
* Use of concomitant medications that interacts with tacrolimus according to the SPC, including but not limited to strong CYP3A4 inhibitors (i.e. azoles, protease inhibitors) or CYP3A4 inducers (rifampicin, phenytoin, carbamazepine), barbiturates, macrolides, digoxin, statins, PPI inhibitors, ergotamine, tricyclic antidepressants, herbal supplements (St. John's wort, extracts of Schisandra sphenanthera)
* Inability to swallow capsules
* Already taking the IMP in this comparison
* Known hypersensitivity, including lactose and gelatin intolerance, or adverse reaction to the active substances and their excipients (as per SPCs for this comparison) or any past medical history contraindicating use of the IMP in this comparison
* Receipt of a live attenuated vaccine within four weeks prior to receipt of tacrolimus. These include, but are not limited to live influenza vaccine (Fluenz Tetra), Shingles (varicella zoster virus) Zostavax, Varicella (Varilrix, Varilvax), Oral typhoid (Ty21a), and yellow fever vaccines.
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
University College, London
OTHER
University of Warwick
OTHER
NHS Lothian
OTHER_GOV
University of Edinburgh
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Professor Chandran
Role: STUDY_DIRECTOR
University of Edinburgh
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Southern Health and Social Care Trust, Craigavon Area Hospital
Portadown, County Armagh, United Kingdom
Aberdeen Royal Infirmary
Aberdeen, , United Kingdom
University Hospitals of Birmingham NHS Foundation Trust
Birmingham, , United Kingdom
University Hospitals Sussex NHS Foundation Trust
Brighton, , United Kingdom
West Suffolk NHS Foundation Trust
Bury St Edmunds, , United Kingdom
Cambridge University Hospitals NHS Foundation Trust
Cambridge, , United Kingdom
Cardiff and Vale University Local Health Board
Cardiff, , United Kingdom
Clinical Research Centre , Ninewells Hospital
Dundee, , United Kingdom
Anne Rowling Regenerative Neurology Clinic
Edinburgh, , 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, , United Kingdom
Royal London Hospital
London, , United Kingdom
St George's University Hospitals NHS Foundation Trust
London, , United Kingdom
King's College Hospital NHS Foundation Trust
London, , United Kingdom
Newcastle upon Tyne Hospitals NHS Foundation Trust
Newcastle upon Tyne, , United Kingdom
Norfolk and Norwich University Hospitals NHS Foundation Trust
Norwich, , 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
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Raeburn Forbes
Role: primary
Callum Duncan
Role: primary
Venkatamaran Srinivasan
Role: primary
Francesca Crawley
Role: primary
Rhys Roberts
Role: primary
Ken Dawson
Role: primary
Ian Morrison
Role: primary
Timothy Harrower
Role: primary
George Gorrie
Role: primary
Javier Carod Artal
Role: primary
Clare Galton
Role: primary
Aleks Radunovic
Role: primary
Pablo Garcia Reitboeck
Role: primary
Tim Williams
Role: primary
Godwin Mamutse
Role: primary
Hisham Hamdalla
Role: primary
Christopher McDermott
Role: primary
Ashwin Pinto
Role: primary
References
Explore related publications, articles, or registry entries linked to this study.
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.
Wong 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.
Parker 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.
Wong 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.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
AC18082
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.