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Motor Neurone Disease - Systematic Multi-Arm Adaptive Randomised Trial (MND-SMART)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04302870
Recruitment Status : Recruiting
First Posted : March 10, 2020
Last Update Posted : March 10, 2020
Sponsor:
Collaborators:
University College, London
University of Warwick
NHS Lothian
Information provided by (Responsible Party):
University of Edinburgh

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
Motor Neuron Disease, Amyotrophic Lateral Sclerosis Drug: Memantine Hydrochloride Oral Solution Drug: Trazodone Hydrochloride oral solution Drug: Placebo oral solution Phase 2 Phase 3

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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




Primary Outcome Measures :
  1. Change in decline of ALS-FRS(R) over 18months [ Time Frame: 18 months ]
    Co-primary outcome measure

  2. Survival [ Time Frame: 18 months ]
    Co-primary outcome measure


Secondary Outcome Measures :
  1. Cognition and behaviour [ Time Frame: 18 months ]
    Using Edinburgh Cognitive and Behavioural ALS Screen (ECAS)

  2. Respiratory function - Forced vital capacity [ Time Frame: 18 months ]
    Change in FVC

  3. King's ALS Clinical stage [ Time Frame: 18 months ]
    Time to reach King's stage IV, scale range I - V

  4. Changes in anxiety and depression [ Time Frame: 18 months ]
    Measured using the hospital anxiety and depression scale (HADS), scale range 0 - 42

  5. Changes in Quality of Life [ Time Frame: 18 months ]
    Measured using EQ-5D-5L

  6. Safety and tolerability of IMPs [ Time Frame: 18 months ]
    Measured using adverse events

  7. Respiratory function - Sniff nasal inspiratory pressure [ Time Frame: 18 months ]
    Change in SNIP



Information from the National Library of Medicine

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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • 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 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).

Information from the National Library of Medicine

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


Contacts
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Contact: Professor Chandran 0131 465 9612 siddharthan.chandran@ed.ac.uk
Contact: Rachel Dakin 0131 465 9612 rachel.dakin@Ed.ac.uk

Locations
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United Kingdom
Anne Rowling Regenerative Neurology Clinic Recruiting
Edinburgh, United Kingdom, EH16 4SB
Contact: Judith Newton    0131 242 7985    lothian.mndsmart@nhs.net   
Sponsors and Collaborators
University of Edinburgh
University College, London
University of Warwick
NHS Lothian
Investigators
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Study Director: Professor Chandran University of Edinburgh
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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: March 10, 2020
Last Verified: March 2020

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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
Additional relevant MeSH terms:
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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