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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01910259
• Date of registration: 19/07/2013
• Prospective Registration: Yes
• Primary sponsor: University College, London
• Public title: MS-SMART: Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial MS-SMART
• Scientific title: A Multi-arm Phase IIB Randomised, Double Blind Placebo-controlled Clinical Trial Comparing the Efficacy of Three Neuroprotective Drugs in Secondary Progressive Multiple Sclerosis.
• Date of first enrolment: December 18, 2014
• Target sample size: 445
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01910259
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

United Kingdom

Contacts

• Name: Jeremy Chataway
• Affiliation: University College, London

• Name: Siddharthan Chandran
• Affiliation: University of Edinburgh

Key inclusion & exclusion criteria

Inclusion Criteria:

- Confirmed diagnosis of SPMS. Steady progression rather than relapse must be the major
cause of increasing disability in the preceding 2 years. Evidence of progression,
either an increase of at least one point in EDSS or clinical documentation of
increasing disability in patient notes

- Expanded Disability Status Scale (EDSS) 4.0-6.5

- Aged 25 to 65 inclusive

- Women and men with partners of childbearing potential 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

- Women must have a negative pregnancy test within 7 days prior to the 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 (e.g. can tolerate MRI and fulfils
the requirements for MRI, e.g. not fitted with pacemakers or permanent hearing aids),
ability to understand and complete questionnaires

- Written informed consent provided

Exclusion Criteria:

- Pregnancy or breast feeding patients

- Baseline MRI scan not of adequate quality for analysis (e.g. too much movement
artefact)

- Significant organ co-morbidity (e.g. malignancy or renal or hepatic failure)

- Relapse within 3 months of baseline visit

- Patients who have been treated with iv or oral steroids for an MS relapse/progression
within 3 months of baseline visit (these patients can undergo future screening visits
once the 3 month window has expired), patients on steroids for another medical
condition may enter as long as the steroid prescription is not for multiple sclerosis
(relapse/ progression).

- Use of Simvastatin at 80mg dose within 3 months of baseline visit (lower doses of
Simvastatin and other statins are permissible)

- Commencement of fampridine within 6 months of baseline visit

- Use of immunosuppressants (e.g. azathioprine, methotrexate, cyclosporine) or disease
modifying treatments (ß-interferons, glatiramer) within 6 months of baseline visit

- Use of fingolimod/fumarate/teriflunomide/laquinomod/or other experimental disease
modifying treatment (including research of an investigational medicinal product)
within 12 months of baseline visit

- Use of mitoxantrone/ natalizumab/ alemtuzumab/ daclizumab if treated within 12 months
of baseline visit

- Primary progressive MS

- Relapsing-remitting MS

- Known hypersensitivity to the active substances and their excipients to any of the
active drugs for this trial

- Use of: lithium, chlorpropamide, triamterene and spironolactone within 6 months of the
baseline visit

- Current use of potassium supplements

- Current use of tamoxifen

- Current use of herbal treatments containing St. John's Wort

- Significant signs of depression

- Use of an SSRI within 6 months of the baseline visit

- Use of monoamine oxidase inhibitors, phenytoin, L-tryptophan) and/or neuroleptic drugs
within 6 months of the baseline visit

- A Beck Depression Index score of 19 or higher

- Bipolar disorder

- Receiving or previously received Electro-Convulsive Therapy

- Epilepsy/seizures

- Glaucoma

- Patients with a history of bleeding disorders or currently on anticoagulants Routine
screening blood values (LFT) >/ 3 x upper limit of normal (ULN) of site reference
ranges (ALT/AST, bilirubin,?GT) Potassium <2.8mmol/l or >5.5mmol/l

- Sodium <125mmol/l

- Creatinine >130µmol/l

- WBCs <3 x 109/l

- Lymphocytes <0.8 x 109/l

- Neutrophil count <1.0 x 109 /l

- Platelet count <90 x 109 /l

- Haemoglobin <80g/l



Age minimum: 25 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Secondary Progressive Multiple Sclerosis

Intervention(s)

Drug: Amiloride

Drug: Riluzole

Drug: Fluoxetine

Drug: Placebo

Primary Outcome(s)

MRI-derived Percentage Brain Volume Change (PBVC). [Time Frame: 2 years]

Secondary Outcome(s)

Count of new and enlarging T2 lesions [Time Frame: 2 years]

Multi-arm trial strategy assessment [Time Frame: 2 years]

Pseudo-atrophy [Time Frame: 6 months]

Clinical measure of neuroprotection [Time Frame: 2 years]

Health economics [Time Frame: 2 years]

Secondary ID(s)

12/0219

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

MS Society

Queen Mary University of London

University of Warwick

University of Sheffield

Keele University

Medical Research Council

University of Edinburgh

University of Leeds

National Institute for Health Research, United Kingdom