MND-SMART

Motor neurone disease systematic multi-arm adaptive randomised trial (MND-SMART)

UK Chief Investigator

Professor Siddharthan Chandran

Research summary

MND-SMART stands for Motor Neuron Disease – Systematic Multi-arm Adaptive Randomised Trial. The study is a platform trial.

Multi-arm means that, unlike typical clinical trials which test a single treatment, MND-SMART will test more than one at the same time. Trial participants taking the different treatments will be compared with a single group who receive a dummy drug, called a placebo. This means that people in MND-SMART are more likely to receive an active treatment when compared to standard clinical trials where half of participants receive the placebo and half the active treatment.

The trial is also adaptive so that researchers can change the drugs being tested according to emerging results. This means that new medicines can be added once a trial has started, while treatments that do not prove effective can be dropped. This is a phase 2 / 3 trial which means if drugs appear to be effective, they will seamlessly transition into phase 3 without the need for additional permissions or trial participants needing to complete a phase 2 trial and join a separate phase 3 trial.

This trial is placebo-controlled. It is important to understand what this means. Click the links to go to the glossary of terms and read further explanations.

When considering taking part in any clinical trial, it is important to consider:

What the chances are of you being randomly assigned to either an intervention group or a placebo group
How long you would remain on this treatment allocation
If the study offers an open-label extension on completion of the main study.

Current status

Open to recruitment

Recruitment target

Up to 800 participants

Click here to see how many patients have been recruited into this study to date (external link to the NIHR public study search)

Recruitment group(s)

Patients with MND

Locations

Scotland:

Aberdeen, Principal Investigator: Callum Duncan. Site open for local recruitment only
Dundee, Principal Investigator: Ian Morrison. Site open for local recruitment only
Edinburgh, Principal Investigator: Suvankar Pal. Site open for local recruitment only
Glasgow, Principal Investigator: George Gorrie. Site open for local recruitment only
Inverness, Principal Investigator: Javier Carod Artal. Site open for local recruitment only

England:

Birmingham, Principal Investigator: Venkatamaran Srinivasan. To be confirmed if site is open for recruitment locally or out-of-area
Brighton, Principal Investigator: Andrew Barritt. Site open for local recruitment only
Bury St Edmunds, Principal Investigator: Francesca Crawley. To be confirmed if site is open for recruitment locally or out-of-area
Cambridge, Principal Investigator: Rhys Roberts. To be confirmed if site is open for recruitment locally or out-of-area
Exeter, Principal Investigator: Tim Harrower. To be confirmed if site is open for recruitment locally or out-of-area
Ipswich, Principal Investigator: Clare Galton. To be confirmed if site is open for recruitment locally or out-of-area
London - St George's Hospital, Principal Investigator: Pablo Garcia Reitboeck. Site potentially open for recruitment out-of-area
London - Royal London Hospital, Principal Investigator: Aleks Radunovic. To be confirmed if site is open for recruitment locally or out-of-area
London - University College Hospital, Principal Investigator: Andrea Malaspina. Site open for recruitment out-of-area
London - King's College Hospital, Principal Investigator: Ammar Al-Chalabi. Site open for recruitment out-of-area
Newcastle, Principal Investigator: Tim Williams. Site open for local recruitment only
Norwich, Principal Investigator: Godwin Mamutse. Site open for recruitment out-of-area
Poole, Principal Investigator: Charles Hillier. To be confirmed if site is open for recruitment locally or out-of-area
Salford, Principal Investigator: Hisham Hamdalla. Site open for recruitment out-of-area
Sheffield, Principal Investigator: Chris McDermott. Site open for local recruitment only
Southampton, Principal Investigator: Ashwin Pinto. To be confirmed if site is open for recruitment locally or out-of-area

Wales:

Cardiff, Principal Investigator: Ken Dawson. To be confirmed if site is open for recruitment locally or out-of-area

Northern Ireland:

Craigavon Area Hospital, Principal Investigator: Raeburn Forbes. To be confirmed if site is open for recruitment locally or out-of-area

Information about study sites

Contact details

Website: www.mnd-smart.org

Email: loth.mndsmart@nhslothian.scot.nhs.uk

Telephone: 0131 242 9122

Key dates

Recruitment open date: 20 February 2020

Planned recruitment end date: 02 November 2026

Inclusion / exclusion 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 Clinical Trials Facilitation and coordination Group (CTFG) guidelines. Must have a negative pregnancy test within seven 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 four 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 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 (C-SSRS).
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) <35 ml/min.
If Serum free T4 >25pmol/l or TSH <0.2mU/l.
If corrected QT interval on 12 lead ECG >500 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.
Patients with active epilepsy.
Patients with history of proven peptic ulcer confirmed on endoscopy.

Funders

MND Scotland
Euan MacDonald Centre for MND Research
My Name'5 Doddie Foundation

Sponsor

NHS Lothian

Study design

Interventional; multi-arm, multi-stage, adaptive, randomised controlled trial

Current interventions

Drug: Amantadine
Placebo

Phase

2/3

Outcome measures

Co-primary outcome measures

Slope of decline in Amyotrophic Lateral Sclerosis Functional Rating Scale (Revised) (ALS-FRS(R)) over 18 months.
Survival.

Secondary outcomes

Time to King's stage 4a (nutritional failure).
Time to King's stage 4b (respiratory failure).
Cognitive function and behaviour assessed by the Edinburgh Cognitive and Behavioural ALS Screen (ECAS).
Respiratory function measured by forced vital capacity (FVC) and sniff nasal inspiratory pressure (SNIP).
Anxiety and depression measured by the Hospital Anxiety and Depression Scale (HADS).
Quality of life evaluation – EQ-5D-5L.