Motor Neurone Disease - Systematic Multi-Arm Adaptive Randomised Trial

Minimum Age:

18 Years

Maximum Age:

N/A

Inclusion Criteria:

- 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)

Exclusion Criteria:

- 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.