- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04302870
Motor Neurone Disease - Systematic Multi-Arm Adaptive Randomised Trial (MND-SMART)
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. The trial started with 3 arms; drug 1 (memantine), drug 2 (trazodone) and placebo (dummy drug). A third drug, amantadine, was added in April 2023. The first two drugs, memantine and trazodone, were removed from the trial in September 2023 due to lack of benefit. The trial currently has 2 recruiting arms; amantadine and placebo. This allows the evaluation of each drug versus placebo. Participants will be randomly allocated to either of the recruiting arms. 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 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. These can be added by substantial amendment to the protocol.
Study Overview
Status
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Contact
- Name: Professor Chandran
- Phone Number: 0131 465 9612
- Email: siddharthan.chandran@ed.ac.uk
Study Contact Backup
- Name: Amy Stenson
- Phone Number: 0131 242 9122
- Email: astenson@exseed.ed.ac.uk
Study Locations
-
-
-
Aberdeen, United Kingdom
- Recruiting
- Aberdeen Royal Infirmary
-
Contact:
- Callum Duncan
-
Birmingham, United Kingdom, B15 2TH
- Recruiting
- University Hospitals of Birmingham NHS Foundation Trust
-
Contact:
- Venkatamaran Srinivasan
-
Brighton, United Kingdom
- Recruiting
- University Hospitals Sussex NHS Foundation Trust
-
Principal Investigator:
- Andrew Barritt
-
Bury Saint Edmunds, United Kingdom, IP33 2QZ
- Recruiting
- West Suffolk NHS Foundation Trust
-
Contact:
- Francesca Crawley
-
Cambridge, United Kingdom, CB2 0QQ
- Recruiting
- Cambridge University Hospitals NHS Foundation Trust
-
Contact:
- Rhys Roberts
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Cardiff, United Kingdom, CF14 4XW
- Recruiting
- Cardiff and Vale University Local Health Board
-
Contact:
- Ken Dawson
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Dundee, United Kingdom
- Recruiting
- Clinical Research Centre , Ninewells Hospital
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Contact:
- Ian Morrison
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Edinburgh, United Kingdom, EH16 4SB
- Recruiting
- Anne Rowling Regenerative Neurology Clinic
-
Contact:
- Judith Newton
- Phone Number: 0131 465 9517
- Email: loth.mndsmart@nhslothian.scot.nhs.uk
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Exeter, United Kingdom
- Recruiting
- Royal Devon and Exeter Hospital
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Contact:
- Timothy Harrower
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Glasgow, United Kingdom
- Recruiting
- Queen Elizabeth University Hospital Clinical Research Facility
-
Contact:
- George Gorrie
-
Inverness, United Kingdom
- Recruiting
- NHS Highland Clinical Research Facility, Raigmore Hospital
-
Contact:
- Javier Carod Artal
-
Ipswich, United Kingdom, CO4 5JL
- Recruiting
- East Suffolk and North Essex NHS Foundation Trust
-
Contact:
- Clare Galton
-
London, United Kingdom
- Recruiting
- King's College Hospital NHS Foundation Trust
-
Principal Investigator:
- Ammar Al-Chalabi
-
London, United Kingdom, SW17 0QT
- Recruiting
- St George's University Hospitals NHS Foundation Trust
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Contact:
- Pablo Garcia Reitboeck
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London, United Kingdom, E1 1FR
- Recruiting
- Royal London Hospital
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Contact:
- Aleks Radunovic
-
Newcastle Upon Tyne, United Kingdom, NE7 7DN
- Recruiting
- Newcastle upon Tyne Hospitals NHS Foundation Trust
-
Contact:
- Tim Williams
-
Norwich, United Kingdom, NR4 7UY
- Recruiting
- Norfolk and Norwich University Hospitals NHS Foundation Trust
-
Contact:
- Godwin Mamutse
-
Poole, United Kingdom
- Recruiting
- University Hospitals of Dorset NHS Trust
-
Principal Investigator:
- Charles Hillier
-
Salford, United Kingdom
- Recruiting
- Clinical Research Facility Salford Royal NHS Foundation Trust
-
Contact:
- Hisham Hamdalla
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Sheffield, United Kingdom
- Recruiting
- Sheffield Teaching Hospitals NHS Foundation Trust
-
Contact:
- Christopher McDermott
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Southampton, United Kingdom
- Recruiting
- Clinical Research Facility University Hospital Southampton
-
Contact:
- Ashwin Pinto
-
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County Armagh
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Portadown, County Armagh, United Kingdom, BT63 5QQ
- Recruiting
- Southern Health and Social Care Trust, Craigavon Area Hospital
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Contact:
- Raeburn Forbes
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
|
Placebo taken once daily
|
Experimental: Memantine
|
Memantine hydrocholoride taken once daily
|
Experimental: Trazodone
|
Trazodone Hydrochloride taken once daily
|
Experimental: Amantadine
|
Amantadine Hydrochloride taken once daily
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in decline of ALS-FRS(R) over 18months
Time Frame: 18 months
|
Co-primary outcome measure
|
18 months
|
Survival
Time Frame: 18 months
|
Co-primary outcome measure
|
18 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cognition and behaviour
Time Frame: 18 months
|
Using Edinburgh Cognitive and Behavioural ALS Screen (ECAS)
|
18 months
|
Respiratory function - Forced vital capacity
Time Frame: 18 months
|
Change in FVC
|
18 months
|
King's ALS Clinical stage
Time Frame: 18 months
|
Time to reach King's stage IV, scale range I - V
|
18 months
|
Changes in anxiety and depression
Time Frame: 18 months
|
Measured using the hospital anxiety and depression scale (HADS), scale range 0 - 42
|
18 months
|
Changes in Quality of Life
Time Frame: 18 months
|
Measured using EQ-5D-5L
|
18 months
|
Safety and tolerability of IMPs
Time Frame: 18 months
|
Measured using adverse events
|
18 months
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Professor Chandran, University of Edinburgh
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neuromuscular Diseases
- Neurodegenerative Diseases
- Spinal Cord Diseases
- TDP-43 Proteinopathies
- Proteostasis Deficiencies
- Motor Neuron Disease
- Amyotrophic Lateral Sclerosis
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Antiviral Agents
- Analgesics
- Sensory System Agents
- Excitatory Amino Acid Antagonists
- Excitatory Amino Acid Agents
- Analgesics, Non-Narcotic
- Tranquilizing Agents
- Psychotropic Drugs
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Serotonin Agents
- Antidepressive Agents
- Dopamine Agents
- Anti-Anxiety Agents
- Antidepressive Agents, Second-Generation
- Antiparkinson Agents
- Anti-Dyskinesia Agents
- Selective Serotonin Reuptake Inhibitors
- Pharmaceutical Solutions
- Memantine
- Amantadine
- Trazodone
Other Study ID Numbers
- AC18082
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
To ensure data transparency, the results of any closed comparisons will be published in a peer reviewed journal as soon as it is possible when the integrity of the trial will not be affected.
Individual level participant data will be shared ,after deidentification, upon receipt of a valid request.
Some data may be shared prior to the publication of study results depending on the requirements, however no end point data will be released without explicit need and permission from the TSC.
Each data request form will be individually reviewed to ensure the proposal has a valid rationale and appropriate methodology. Only data required for the project will be shared.
A summary of results will be provided to all participants via newsletters and the trial website.
IPD Sharing Time Frame
IPD Sharing Access Criteria
Data will be shared with researchers who provide a methodologically sound proposal to achieve the aims of the proposal only.
Data sharing request forms are available from mnd-smart@Ed.ac.uk. Requesters will need to sign a data access agreement prior to being provided with access to data.
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- ANALYTIC_CODE
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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