This study is currently in set-up; the first participants are due to be recruited in Spring 2020.
|Study title||Motor Neurone Disease Systematic Multi-arm Adaptive Randomised Trial (MND-SMART)|
|UK Chief Investigator||Professor Siddharthan Chandran|
|Research 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. In the first instance the trial will have 3 arms; drug 1, drug 2 and placebo (dummy drug). This allows the evaluation of drug 1 versus placebo and separately drug 2 versus placebo. Participants will be randomly allocated to either drug 1, drug 2 or placebo. Medicines being tested are already approved for use in other conditions. This approach is called drug repurposing.
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 first 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.
|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 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).
• 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) <30 ml/min
• If Serum free T4 >25pmol/l or TSH <0.2mU/l
• If corrected QT interval on 12 lead ECG >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).
|Current status||Open to recruitment|
Other sites are due to open later in the year.
|Contact details||Website: www.mnd-smart.org
Telephone: 07341 887 737
|Recruitment group(s)||Patients with MND.|
|Recruitment target(s)||Up to 750 participants.|
|Key dates||Actual opening date: 20 February 2020
Recruitment planned end date: 16 December 2022
|Funder(s)||MND Scotland, Euan MacDonald Centre for MND Research, My Name'5 Doddie Foundation.|
|Study design||Interventional; multi-arm, multi-stage, adaptive, randomised controlled trial|
|Intervention (if applicable)||Drug: Trazodone
|Phase (if applicable)||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
- 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.
|Publications / Results reports||Links will be provided when papers are published.|
|Participant Information Sheet|