MND-SMART: Motor Neurone Disease - Systematic Multi-Arm Adaptive Randomised Trial
Study Details
Study Description
Brief 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.
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Memantine
|
Drug: Memantine Hydrochloride Oral Solution
Memantine hydrocholoride taken once daily
|
| Experimental: Trazodone
|
Drug: Trazodone Hydrochloride oral solution
Trazodone Hydrochloride taken once daily
|
| Placebo Comparator: Placebo
|
Drug: Placebo oral solution
Placebo taken once daily
|
Outcome Measures
Primary Outcome Measures
- Change in decline of ALS-FRS(R) over 18months [18 months]
Co-primary outcome measure
- Survival [18 months]
Co-primary outcome measure
Secondary Outcome Measures
- Cognition and behaviour [18 months]
Using Edinburgh Cognitive and Behavioural ALS Screen (ECAS)
- Respiratory function - Forced vital capacity [18 months]
Change in FVC
- King's ALS Clinical stage [18 months]
Time to reach King's stage IV, scale range I - V
- Changes in anxiety and depression [18 months]
Measured using the hospital anxiety and depression scale (HADS), scale range 0 - 42
- Changes in Quality of Life [18 months]
Measured using EQ-5D-5L
- Safety and tolerability of IMPs [18 months]
Measured using adverse events
Eligibility Criteria
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, 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
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If ALT, ALP, bilirubin or GGT >3 times the upper limit of normal.
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If creatinine clearance (creatinine clearance or eGFR) <30 ml/min.
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If TSH <0.2mU/l (if possible to test free T4, then Serum free T4 >25pmol/l)
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If corrected QT interval on 12 lead ECG >450 ms
-
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
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Patient's contraindicated to any of the IMPs according to SPC section 4.3
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Aberdeen Royal Infirmary | Aberdeen | United Kingdom | ||
| 2 | Clinical Research Centre , Ninewells Hospital | Dundee | United Kingdom | ||
| 3 | Anne Rowling Regenerative Neurology Clinic | Edinburgh | United Kingdom | EH16 4SB | |
| 4 | Royal Devon and Exeter Hospital | Exeter | United Kingdom | ||
| 5 | Queen Elizabeth University Hospital Clinical Research Facility | Glasgow | United Kingdom | ||
| 6 | NHS Highland Clinical Research Facility, Raigmore Hospital | Inverness | United Kingdom | ||
| 7 | Clinical Research Facility Salford Royal NHS Foundation Trust | Salford | United Kingdom | ||
| 8 | Clinical Research Facility University Hospital Southampton | Southampton | United Kingdom |
Sponsors and Collaborators
- University of Edinburgh
- University College, London
- University of Warwick
- NHS Lothian
Investigators
- Study Director: Professor Chandran, University of Edinburgh
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AC18082