MS-SMART: Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial

Summary

Multiple sclerosis (MS) is a disabling and progressive neurological disease that affects approximately 100,000 people in the UK. Many patients with MS experience two phases of disease; early MS (also called relapsing remitting MS, RRMS) and late MS (also called secondary progressive MS (SPMS). Early MS is due to inflammation of the nerves and the insulation (called myelin) that surrounds the nerves. Early MS is often characterised by periods of "attacks" interspersed with periods of "remission" with no or low disease symptoms. Late or progressive MS, which affects the majority of patients and typically emerges after 10-15 years of disease, results from actual nerve death (also called neurodegeneration). The progressive stage of disease results not in individual attacks but slow, cumulative and irreversible disability affecting walking, balance, vision, cognition, pain control, bladder and bowel function. Critically, and unlike early disease, there is no proven treatment for the late stage of MS. This is therefore an urgent and major unmet health need. MS-SMART directly addresses this need and will evaluate in this clinical trial three drugs (fluoxetine, riluzole or amiloride), all of which have shown some promise in MS, and in particular in SPMS. The trial is randomised and blinded. Randomisation means patients can get any one of the three active drugs or the inactive placebo/dummy; blinded means that neither patients nor the doctors will know which drug or placebo patients are receiving. Randomisation and blinding are standard approaches in clinical trials to ensure unbiased testing of drugs. All patients in MS-SMART will have periodic MRI (magnetic resonance imaging) brain scans and after 96 weeks these will be analysed. We will then compare the scans of each drug to the placebo or dummy to see if any of the drugs slow the rate of brain shrinkage that normally occurs in SPMS. This measured change in brain size is the primary (major) outcome of MS-SMART.

Conditions

• Secondary Progressive Multiple Sclerosis

Interventions

DRUG

Amiloride

Comparison with placebo

DRUG

Riluzole

Comparison with placebo

DRUG

Fluoxetine

Comparison with placebo

DRUG

Placebo

Placebo comparator

Sponsors & Collaborators

• Medical Research Council

  collaborator OTHER_GOV

• National Institute for Health Research, United Kingdom

  collaborator OTHER_GOV

• National Multiple Sclerosis Society

  collaborator OTHER

• University of Edinburgh

  collaborator OTHER

• Queen Mary University of London

  collaborator OTHER

• Keele University

  collaborator OTHER

• University of Sheffield

  collaborator OTHER

• University of Leeds

  collaborator OTHER

• University of Warwick

  collaborator OTHER

• University College, London

  lead OTHER

Principal Investigators

• Jeremy Chataway · University College, London

• Siddharthan Chandran · University of Edinburgh

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

25 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-12-18

Primary Completion

2018-06-14

Completion

2018-07-04

Countries

• United Kingdom

Study Locations