Motor Neurone Disease - Systematic Multi-Arm Adaptive Randomised Trial
- Conditions
- Motor Neuron Disease, Amyotrophic Lateral Sclerosis
- Interventions
- Registration Number
- NCT04302870
- Lead Sponsor
- University of Edinburgh
- Brief Summary
MND-SMART is investigating whether selected drugs can slow down the progression of motor neurone 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. The first two drugs, memantine and trazodone, were removed from the trial in September 2023 due to lack of benefit. The trial currently has 2 recruiting arms; amantadine and placebo. This allows the evaluation of each drug versus placebo. Participants will be randomly allocated to either of the recruiting arms. 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.
- Detailed Description
For further information, please visit: https://mnd-smart.org/
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 800
- Confirmed diagnosis of MND (including the following subtypes: ALS by El Escorial Criteria (possible, probable, and definite), Primary Lateral Sclerosis, and Progressive Muscular Atrophy)
- Over 18
- Women of childbearing potential according to Clinical Trials Facilitation and Coordination Group (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 (this can be signed by a proxy in the case of limb dysfunction)
- Patients diagnosed with Frontotemporal Dementia (FTD-MND) or any other significant psychiatric disorder that prevents informed consent being given.
- Patients in the manic phase of bipolar disorder.
- Alcoholism (self-reported)
- Active suicide ideation assessed using the Columbia-Suicide Severity Rating Scale
- On concurrent investigational medication (including biological therapy)
- Known hypersensitivity, including hereditary fructose intolerance, or adverse reaction to the active substances and their excipients (SPCs section 6.1) or any past medical history contraindicating use of any of the IMPs
- 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)
- corrected QT interval on 12 lead ECG >500 ms
- Active Epilepsy
- History of proven peptic ulcer confirmed on endoscopy
- 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).
- Already taking any of the IMPs in this protocol
- Patient's contraindicated to any of the IMPs according to SPC section 4.3
- Taking a medication that interacts with the active substances and their excipients according to the SPCs, including but not limited to; Dextromethorphan, Amantadine; Ketamine, Monoamineoxidase inhibitors ((MAOIs), Rasagiline, Selegiline, Safinamide, Tranylcypromine, Phenelzine, Isocarboxazid, Moclobemide).
- Patients who the PI considers will not be able to comply with the study protocol.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo oral solution - Amantadine Amantadine Hydrochloride Oral Solution - Trazodone Trazodone Hydrochloride oral solution - Memantine Memantine Hydrochloride Oral Solution -
- Primary Outcome Measures
Name Time Method Change in decline of ALS-FRS(R) over 18months 18 months Co-primary outcome measure
Survival 18 months Co-primary outcome measure
- Secondary Outcome Measures
Name Time Method Cognition and behaviour 18 months Using Edinburgh Cognitive and Behavioural ALS Screen (ECAS)
Respiratory function - Forced vital capacity 18 months Change in FVC
King's ALS Clinical stage 18 months Time to reach King's stage IV, scale range I - V
Changes in anxiety and depression 18 months Measured using the hospital anxiety and depression scale (HADS), scale range 0 - 42
Changes in Quality of Life 18 months Measured using EQ-5D-5L
Safety and tolerability of IMPs 18 months Measured using adverse events
Trial Locations
- Locations (22)
Southern Health and Social Care Trust, Craigavon Area Hospital
🇬🇧Portadown, County Armagh, United Kingdom
West Suffolk NHS Foundation Trust
🇬🇧Bury Saint Edmunds, United Kingdom
Clinical Research Centre , Ninewells Hospital
🇬🇧Dundee, United Kingdom
Anne Rowling Regenerative Neurology Clinic
🇬🇧Edinburgh, United Kingdom
Queen Elizabeth University Hospital Clinical Research Facility
🇬🇧Glasgow, United Kingdom
St George's University Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
King's College Hospital NHS Foundation Trust
🇬🇧London, United Kingdom
University Hospitals of Dorset NHS Trust
🇬🇧Poole, United Kingdom
Clinical Research Facility University Hospital Southampton
🇬🇧Southampton, United Kingdom
Clinical Research Facility Salford Royal NHS Foundation Trust
🇬🇧Salford, United Kingdom
Sheffield Teaching Hospitals NHS Foundation Trust
🇬🇧Sheffield, United Kingdom
Aberdeen Royal Infirmary
🇬🇧Aberdeen, United Kingdom
University Hospitals of Birmingham NHS Foundation Trust
🇬🇧Birmingham, United Kingdom
Cardiff and Vale University Local Health Board
🇬🇧Cardiff, United Kingdom
Cambridge University Hospitals NHS Foundation Trust
🇬🇧Cambridge, United Kingdom
Royal Devon and Exeter Hospital
🇬🇧Exeter, United Kingdom
East Suffolk and North Essex NHS Foundation Trust
🇬🇧Ipswich, United Kingdom
NHS Highland Clinical Research Facility, Raigmore Hospital
🇬🇧Inverness, United Kingdom
Newcastle upon Tyne Hospitals NHS Foundation Trust
🇬🇧Newcastle Upon Tyne, United Kingdom
University Hospitals Sussex NHS Foundation Trust
🇬🇧Brighton, United Kingdom
Norfolk and Norwich University Hospitals NHS Foundation Trust
🇬🇧Norwich, United Kingdom
Royal London Hospital
🇬🇧London, United Kingdom