MS-SMART: Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial
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 (ibudilast, 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.
- Male or female and aged 25 Years to 65 Years
- Confirmed diagnosis of SPMS at randomisation
- Steady progression rather than relapse must be the major cause of increasing disability in the preceding 2 years. Progression can be evident from either an increase of at least one point in EDSS or clinical documentation of increasing disability in patients notes
- EDSS 4.0-6.5
- Men or Women of childbearing age must be using an appropriate method of contraception to avoid any unlikely teratogenic effects of the 3 drugs from time of consent, to 6 weeks after treatment inclusive
- Females have a negative pregnancy test within 7 days prior to being enrolled (baseline visit) unless not of child bearing potential e.g. have undergone a hysterectomy, bilateral tubal ligation or bilateral oophorectomy or they are postmenopausal
- Willing and able to comply with the trial protocol and have the ability to understand and complete questionnaires
- Willing and able to give full written informed consent
- Able to undertake MRI