Study Purpose: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, drug 2 and placebo (dummy drug). The trial currently has 4 arms; drug 1, drug 2, drug 3, and placebo. This allows the evaluation of each drug versus placebo. Participants will be randomly allocated to either drug 1, drug 2, drug 3, or placebo. 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.
Motor Neuron Disease, Amyotrophic Lateral Sclerosis
Type of Intervention:
Memantine Hydrochloride Oral Solution, Trazodone Hydrochloride oral solution, Placebo oral solution, Amantadine Hydrochloride Oral Solution
Phase 2/Phase 3
Study Chair(s)/Principal Investigator(s):
Professor Chandran, University of Edinburgh
Coordinating Center Contact Information
Full Study Summary:
University of Edinburgh
Estimated Study Start Date:
02 / 27 / 2020
Estimated Study Completion Date:
12 / 01 / 2026
Posting Last Modified Date:
04 / 26 / 2023
Date Study Added to neals.org:
03 / 10 / 2020
- 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.
Southern Health and Social Care Trust, Craigavon Area Hospital | Recruiting
Portadown, County Armagh
NHS Highland Clinical Research Facility, Raigmore Hospital | Recruiting
Javier Carod Artal
Clinical Research Facility Salford Royal NHS Foundation Trust | Recruiting
University Hospitals of Dorset NHS Trust | Recruiting
Principal Investigator : Charles Hillier
Norfolk and Norwich University Hospitals NHS Foundation Trust | Recruiting
Norwich NR4 7UY
Newcastle upon Tyne Hospitals NHS Foundation Trust | Recruiting
Newcastle Upon Tyne NE7 7DN
St George's University Hospitals NHS Foundation Trust | Recruiting
Pablo Garcia Reitboeck
London SW17 0QT
Royal London Hospital | Recruiting
London E1 1FR
East Suffolk and North Essex NHS Foundation Trust | Recruiting
Ipswich CO4 5JL
Queen Elizabeth University Hospital Clinical Research Facility | Recruiting
Aberdeen Royal Infirmary | Recruiting
Royal Devon and Exeter Hospital | Recruiting
Anne Rowling Regenerative Neurology Clinic | Recruiting
Edinburgh EH16 4SB
Clinical Research Centre , Ninewells Hospital | Recruiting
Cardiff and Vale University Local Health Board | Recruiting
Cardiff CF14 4XW
Cambridge University Hospitals NHS Foundation Trust | Recruiting
Cambridge CB2 0QQ
West Suffolk NHS Foundation Trust | Recruiting
Bury Saint Edmunds IP33 2QZ
University Hospitals of Birmingham NHS Foundation Trust | Recruiting
Birmingham B15 2TH
Clinical Research Facility University Hospital Southampton | Recruiting