Table 1

Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial eligibility criteria (protocol V.7)

Inclusion criteria
  • Confirmed diagnosis of SPMS. 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.

  • Aged 25–65 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 three 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 childbearing potential (eg, have undergone a hysterectomy, bilateral tubal ligation or bilateral oophorectomy or they are postmenopausal).

  • Willing and able to comply with the trial protocol (eg, can tolerate MRI and fulfils the requirements for MRI, eg, not fitted with pacemakers or permanent hearing aids), ability to understand and complete questionnaires.

  • Written informed consent provided.

Exclusion criteria
  • Pregnancy or breastfeeding patients.

  • Baseline MRI scan not of adequate quality for analysis (eg, too much movement artefact).

  • Significant organ comorbidity (eg, malignancy or renal or hepatic failure).

  • Relapse within 3 months of baseline visit.

  • Patients who have been treated with intravenous 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 will be not for MS (relapse/progression).

  • Use of simvastatin at 80 mg 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 (eg, azathioprine, methotrexate, ciclosporin) or first-generation disease-modifying treatments (β-interferons, glatiramer) within 6 months of baseline visit.

  • Use of fingolimod, fumarate, teriflunomide, laquinimod or other experimental disease-modifying treatment (including research in 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 an SSRI within 6 months of the baseline visit.

  • Current use of tamoxifen.

  • Current use of herbal treatments containing St. John’s wort.

  • Significant signs of depression.

  • Patients with a history of bleeding disorders or currently on anticoagulants.

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

  • Use of lithium, chlorpropamide, triamterene and spironolactone within 6 months of the baseline visit.

  • Current use of potassium supplements.

  • Significant signs of depression bipolar disorder.

  • A Beck Depression Index score of 19 or higher.

  • Epilepsy/seizures.

  • Receiving or previously received electroconvulsive therapy.

  • Glaucoma.

  • Routine screening blood values:

    • LFTs (ALT/AST, bilirubin, gamma-GT)>3x upper limit of normal of site reference ranges.

    • Potassium<2.8 mmol/L or >5.5 mmol/L.

    • Sodium<125 mmol/L.

    • Creatinine>130µmol/L.

    • WBCs<3×109/L.

    • Lymphocytes<0.8×109/L.

    • Neutrophil count<1.0×109/L.

    • Platelet count<90×109/L.

    • Haemoglobin<80 g/L.

  • ALT, Alanine aminotransferase; AST, Aspartate aminotransferase; EDSS, Expanded Disability Status Scale; GT, glutamyl transferase; LFT, liver function test; MS, multiple sclerosis; SPMS, secondary progressive multiple sclerosis; SSRI, selective serotonin-reuptake inhibitor; WBC, white blood cells.