Motor Neurone Disease - Systematic Multi-Arm Adaptive Randomised Trial (MND-SMART)
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| ClinicalTrials.gov Identifier: NCT04302870 |
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Recruitment Status :
Recruiting
First Posted : March 10, 2020
Last Update Posted : May 17, 2022
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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 |
|---|---|---|
| Motor Neuron Disease, Amyotrophic Lateral Sclerosis | Drug: Memantine Hydrochloride Oral Solution Drug: Trazodone Hydrochloride oral solution Drug: Placebo oral solution | Phase 2 Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 750 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | Motor Neurone Disease - Systematic Multi-Arm Adaptive Randomised Trial |
| Actual Study Start Date : | February 27, 2020 |
| Estimated Primary Completion Date : | September 2026 |
| Estimated Study Completion Date : | December 2026 |
| 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 |
- Change in decline of ALS-FRS(R) over 18months [ Time Frame: 18 months ]Co-primary outcome measure
- Survival [ Time Frame: 18 months ]Co-primary outcome measure
- Cognition and behaviour [ Time Frame: 18 months ]Using Edinburgh Cognitive and Behavioural ALS Screen (ECAS)
- Respiratory function - Forced vital capacity [ Time Frame: 18 months ]Change in FVC
- King's ALS Clinical stage [ Time Frame: 18 months ]Time to reach King's stage IV, scale range I - V
- Changes in anxiety and depression [ Time Frame: 18 months ]Measured using the hospital anxiety and depression scale (HADS), scale range 0 - 42
- Changes in Quality of Life [ Time Frame: 18 months ]Measured using EQ-5D-5L
- Safety and tolerability of IMPs [ Time Frame: 18 months ]Measured using adverse events
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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) <30 ml/min.
- If TSH <0.2mU/l (if possible to test free T4, then Serum free T4 >25pmol/l)
- 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
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04302870
| Contact: Professor Chandran | 0131 465 9612 | siddharthan.chandran@ed.ac.uk | |
| Contact: Rachel Dakin | 0131 465 9612 | rachel.dakin@Ed.ac.uk |
| United Kingdom | |
| Aberdeen Royal Infirmary | Recruiting |
| Aberdeen, United Kingdom | |
| Contact: Callum Duncan | |
| Clinical Research Centre , Ninewells Hospital | Recruiting |
| Dundee, United Kingdom | |
| Contact: Ian Morrison | |
| Anne Rowling Regenerative Neurology Clinic | Recruiting |
| Edinburgh, United Kingdom, EH16 4SB | |
| Contact: Judith Newton 0131 242 7985 loth.mndsmart@nhslothian.scot.nhs.uk | |
| Royal Devon and Exeter Hospital | Recruiting |
| Exeter, United Kingdom | |
| Contact: Timothy Harrower | |
| Queen Elizabeth University Hospital Clinical Research Facility | Recruiting |
| Glasgow, United Kingdom | |
| Contact: George Gorrie | |
| NHS Highland Clinical Research Facility, Raigmore Hospital | Recruiting |
| Inverness, United Kingdom | |
| Contact: Javier Carod Artal | |
| Clinical Research Facility Salford Royal NHS Foundation Trust | Recruiting |
| Salford, United Kingdom | |
| Contact: Hisham Hamdalla | |
| Clinical Research Facility University Hospital Southampton | Recruiting |
| Southampton, United Kingdom | |
| Contact: Ashwin Pinto | |
| Study Director: | Professor Chandran | University of Edinburgh |
| Responsible Party: | University of Edinburgh |
| ClinicalTrials.gov Identifier: | NCT04302870 |
| Other Study ID Numbers: |
AC18082 |
| First Posted: | March 10, 2020 Key Record Dates |
| Last Update Posted: | May 17, 2022 |
| Last Verified: | June 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| 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. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) Analytic Code |
| Time Frame: | After publication of study results, no end date. |
| 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. |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
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Motor Neuron Disease Amyotrophic Lateral Sclerosis Neurodegenerative Diseases Nervous System Diseases Neuromuscular Diseases Spinal Cord Diseases Central Nervous System Diseases TDP-43 Proteinopathies Proteostasis Deficiencies Metabolic Diseases Memantine Trazodone Pharmaceutical Solutions Antiparkinson Agents Anti-Dyskinesia Agents |
Dopamine Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Excitatory Amino Acid Antagonists Excitatory Amino Acid Agents Anti-Anxiety Agents Tranquilizing Agents Central Nervous System Depressants Psychotropic Drugs Serotonin Uptake Inhibitors Neurotransmitter Uptake Inhibitors Membrane Transport Modulators Serotonin Agents Antidepressive Agents, Second-Generation |