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

Phase 2

Completed

• Conditions: Topic: Neurological; Subtopic: Neurological (all Subtopics); Nervous System Diseases; Disease: Nervous system disorders; Multiple sclerosis

• Registration Number: ISRCTN28440672
• Lead Sponsor: niversity College London (UK)

Brief Summary

2018 protocol in: https://www.ncbi.nlm.nih.gov/pubmed/30166303 (added 10/04/2019)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-10-25
• Study Completion: 2018-07-04
• Last Update Posted: 8 June 2020

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 445

Inclusion Criteria

Current inclusion criteria as of 24/05/2016:
1. 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
2. EDSS 4.0-6.5
3. Aged 25 to 65 inclusive
4. 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
5. 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)
6. 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
7. Written informed consent

Previous inclusion criteria:
1. Confirmed diagnosis of SPMS at randomisation
2. 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
3. EDSS 4.0-6.5
4. Aged 25 to 65
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 and 6 weeks after treatment
6. Females have a negative pregnancy test within 7 days prior to being enrolled (baseline visit) unless not of child bearing potential eg have undergone a hysterectomy, bilateral tubal ligation or bilateral oophorectomy or they are postmenopausal
7. Willing and able to comply with the trial protocol and have the ability to understand and complete questionnaires
8. Willing and able to give full written informed consent
9. Able to undertake MRI

Exclusion Criteria

Current exclusion criteria as of 24/05/2016:
1. Pregnancy or breast feeding females
2. Baseline MRI scan not of adequate quality for analysis (e.g. too much movement artefact)
3. Significant organ co-morbidity (e.g. malignancy or renal or hepatic failure)
4. Relapse within 3 months of baseline visit
5. 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)
6. Use of Simvastatin at 80mg dose within 3 months of baseline visit (lower doses of Simvastatin and other statins are permissible)
7. Commencement of fampridine within 6 months of baseline visit
8. Use of immunosupressants (e.g. azathioprine, methotrexate, cyclosporine) or first generation disease modifying treatments (ß-interferons, glatiramer) within 6 months of baseline visit
9. Use of fingolimod/fumarate/teriflunomide/laquinomod/or other experimental disease modifying treatment (including research in an investigational medicinal product) within 12 months of baseline visit
10. Use of mitoxantrone/natalizumab/alemtuzumab/daclizumab if treated within 12 months of baseline visit
11. Primary progressive MS
12. Relapsing-remitting MS
13. Known hypersensitivity to the active substances and their excipients to any of the active drugs for this trial
14. Use of an SSRI within 6 months of the baseline visit
15. Current use of tamoxifen
16. Current use of herbal treatments containing St. John’s Wort
17. Patients with a history of bleeding disorders or currently on anticoagulants
18. Use of monoamine oxidase inhibitors, phenytoin, L-tryptophan and/or neuroleptic drugs within 6 months of the baseline visit
19. Use of: lithium, chlorpropamide, triamterene, spironolactone, within 6 months of the baseline visit
20. Current use of potassium supplements
21. Significant signs of depression
22. Bipolar disorder
23. A Beck Depression Index score of 19 or higher
24. Epilepsy/seizures
25. Receiving or previously received Electroconvulsive therapy treatment
26. Glaucoma
27. Routine screening blood values (LFT) >/ 3 x upper limit of normal (ULN) of site reference ranges (AST/ALT, bilirubin, ?GT)
28. Potassium <2.8mmol/l or >5.5mmol/l
29. Sodium <125mmol/l
30. Creatinine >130µmol/l
31. WBCs <3x109/l
32. Lymphocytes <0.8 x 109/l
33. Neutrophil count <1.0 x109 /l
34. Platelet count <90 x109 /l
35. Haemoglobin <80g/l

Previous exclusion criteria:
1. Pregnancy or breast feeding females
2. Patients unable to tolerate baseline MRI scan or scan not of adequate quality for analysis (eg too much movement artefact)
3. Patients fitted with pacemakers or permanent hearing aids

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
MRI-derived Percentage Brain Volume Change (PBVC); Timepoint(s): Baseline, 96 weeks