NCT01910259: MS-SMART

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

Completed Phase 2 Last updated 26 March 2020

What this trial tests

Phase 2 trial testing Amiloride in Secondary Progressive Multiple Sclerosis in 445 participants. Completed in 4 July 2018.

Timeline

18 December 2014

Primary endpoint
14 June 2018

4 July 2018

Quick facts

Lead sponsor	University College, London
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	445
Start date	18 December 2014
Primary completion	14 June 2018
Estimated completion	4 July 2018
Sites	13 locations across United Kingdom

Drugs / interventions tested

• Amiloride (AMILORIDE) — full drug profile →
• Riluzole (RILUZOLE) — full drug profile →
• Fluoxetine (fluoxetine) — full drug profile →
• Placebo

Conditions studied

• Secondary Progressive Multiple Sclerosis — all drugs for Secondary Progressive Multiple Sclerosis →

Sponsor

University College, London

Who can join

Adults 25 to 65, any sex, with Secondary Progressive Multiple Sclerosis. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Clinical trials in progressive multiple sclerosis: lessons learned and future perspectives.
   Ontaneda D, Fox RJ, Chataway J. · · 2015 · cited 161× · PMID 25772899 · DOI 10.1016/s1474-4422(14)70264-9
2. Multiple sclerosis, a treatable disease.
   Doshi A, Chataway J. · · 2016 · cited 120× · PMID 27956442 · DOI 10.7861/clinmedicine.16-6-s53
3. Efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis (MS-SMART): a phase 2b, multiarm, double-blind, randomised placebo-controlled trial.
   Chataway J, De Angelis F, Connick P, Parker RA, et al · · 2020 · cited 93× · PMID 31981516 · DOI 10.1016/s1474-4422(19)30485-5
4. Antidepressants for pain management in adults with chronic pain: a network meta-analysis.
   Birkinshaw H, Friedrich CM, Cole P, Eccleston C, et al · · 2023 · cited 89× · PMID 37160297 · DOI 10.1002/14651858.cd014682.pub2
5. Anti-inflammatory and Neuroprotective Agents in Clinical Trials for CNS Disease and Injury: Where Do We Go From Here?
   Mallah K, Couch C, Borucki DM, Toutonji A, et al · · 2020 · cited 70× · PMID 33013859 · DOI 10.3389/fimmu.2020.02021
6. Evaluating mesenchymal stem cell therapy for sepsis with preclinical meta-analyses prior to initiating a first-in-human trial.
   Lalu MM, Sullivan KJ, Mei SH, Moher D, et al · · 2016 · cited 70× · PMID 27870924 · DOI 10.7554/elife.17850
7. Therapeutic Advances and Future Prospects in Progressive Forms of Multiple Sclerosis.
   Shirani A, Okuda DT, Stüve O. · · 2016 · cited 69× · PMID 26729332 · DOI 10.1007/s13311-015-0409-z
8. Progressive multiple sclerosis: latest therapeutic developments and future directions.
   Faissner S, Gold R. · · 2019 · cited 57× · PMID 31598138 · DOI 10.1177/1756286419878323