Motor Neurone Disease MedDRA version: 20.0 Level: LLT Classification code 10028002 Term: Motor neuron disease System Organ Class: 100000004852
Conditions
Interventions
Product Name: Memantine
Pharmaceutical Form: Oral solution
INN or Proposed INN: memantine hydrochloride
CAS Number: 41100-52-1
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equ
Sponsors
University of Edinburgh
NHS Lothian
Eligibility
Sex/Gender
All
Inclusion criteria
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 CTFG guidelines (http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf) must have a negative pregnancy test within 7 days prior to the baseline visit · Women of childbearing potential and fertile men (according to CTFG guidelines) 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) Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 375 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 375
Exclusion criteria
Exclusion criteria: • Patients diagnosed with Fronto-temporal 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 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) 25pmol/l or TSH 450 ms • Patient’s diagnosed with ventricular arrhythmias, heart block 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 • Taking a medication that interacts with the active substances and their excipients, including but not limited to; Dextromethorphan, Amantadine; Ketamine, Monoamine-oxidase inhibitors ((MAOIs), Rasagiline, Selegiline, Safinamide, Tranylcypromine, Phenelzine, Isocarboxazid, Moclobemide).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine if potential neuroprotective drugs that may fix, regenerate or stabilise the nervous system, can slow the rate of progression of motor neurone disease (MND). This will be measured by assessing the effects the drugs have on patient function, using the ALS Function Rating Scale, and survival. ;Secondary Objective: The secondary objectives are to establish the safety profile of potential neuroprotective drugs in people with MND and also to assess the effects of potential neuroprotective drugs on: o time to nutritional failure, need for a feeding tube o time to respiratory failure, need for some assistance with breathing o cognitive function and behaviour, assessed by the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) o respiratory function measured by forced vital capacity (FVC) and sniff nasal inspiratory pressure (SNIP) o anxiety and depression measured by the Hospital Anxiety and Depression Scale o overall quality of life measured using a standard questionnaire ;Primary end point(s): ALS-FRS and overall survival are co-primary outcome measures and power calculations have been performed for both these outcome measures. To ensure protection of the type I error a closed test procedure will be followed in which overall survival outcome data will only be analysed inferentially for a treatment arm conditional on there being a significant result for ALS-FRS(R) in that treatment arm. In the situation that the ALS-FRS outcome measure does not produce a statistically significant result overall survival data will be analysed to provide supporting information but will not provide pivotal evidence of efficacy. ;Timepoint(s) of evaluation of this end point: ALS-FRS(R) will be measured at baseline and every 2 months for 18 months. After 18 months participants will be followed-up for survival only. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary outcomes are to establish the safety profile of the IMPs in people with MND and also assess the effects of candidate putative neuroprotective drugs on: o time to King’s stage 4a (nutritional failure) o time to King’s stage 4b (respiratory failure) o Cognitive function and behaviour assessed by the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) o Respiratory function measured by forced vital capacity (FVC) and sniff nasal inspiratory pressure (SNIP) o Anxiety and depression measured by the Hospital Anxiety and Depression Scale (HADS) o Quality of life evaluation – EQ-5D-5L ;Timepoint(s) of evaluation of this end point: The timing of evaluation of secondary outcome measure is as below: King's staging will be completed at baseline and every 2 months for 18 months. The ECAS will be completed at baseline, 12 months and 18 months. Respiratory function will be measured at baseline, 6 months, 12 months and 18 months. The HADS and EQ-5D-5L will be completed at baseline, 6 months, 12 months and 18 months. | — |
Countries
United Kingdom
Contacts
Public ContactRachel Dakin
University of Edinburgh
Outcome results
None listed