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

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 (β-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,ˠGT) 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