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

November 28, 2023 updated by: University of Edinburgh

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

Detailed Description

For further information, please visit: https://mnd-smart.org/

Study Type

Interventional

Enrollment (Estimated)

800

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

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
      • Cardiff, United Kingdom, CF14 4XW
        • Recruiting
        • Cardiff and Vale University Local Health Board
        • Contact:
          • Ken Dawson
      • Dundee, United Kingdom
        • Recruiting
        • Clinical Research Centre , Ninewells Hospital
        • Contact:
          • Ian Morrison
      • Edinburgh, United Kingdom, EH16 4SB
      • Exeter, United Kingdom
        • Recruiting
        • Royal Devon and Exeter Hospital
        • Contact:
          • Timothy Harrower
      • 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
        • Contact:
          • Pablo Garcia Reitboeck
      • London, United Kingdom, E1 1FR
        • Recruiting
        • Royal London Hospital
        • 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
      • Sheffield, United Kingdom
        • Recruiting
        • Sheffield Teaching Hospitals NHS Foundation Trust
        • Contact:
          • Christopher McDermott
      • Southampton, United Kingdom
        • Recruiting
        • Clinical Research Facility University Hospital Southampton
        • Contact:
          • Ashwin Pinto
    • County Armagh
      • Portadown, County Armagh, United Kingdom, BT63 5QQ
        • Recruiting
        • Southern Health and Social Care Trust, Craigavon Area Hospital
        • Contact:
          • Raeburn Forbes

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Professor Chandran, University of Edinburgh

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 27, 2020

Primary Completion (Estimated)

September 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

March 4, 2020

First Submitted That Met QC Criteria

March 6, 2020

First Posted (Actual)

March 10, 2020

Study Record Updates

Last Update Posted (Actual)

November 29, 2023

Last Update Submitted That Met QC Criteria

November 28, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

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

After publication of study results, no end date.

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

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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