MS-STAT2 : Multiple Sclerosis - Simvastatin Trial 2
| ISRCTN | ISRCTN82598726 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN82598726 |
| EudraCT/CTIS number | 2017-003328-56 |
| IRAS number | 232288 |
| ClinicalTrials.gov number | NCT03387670 |
| Secondary identifying numbers | CPMS 35831, IRAS 232288 |
- Submission date
- 02/10/2017
- Registration date
- 06/11/2017
- Last edited
- 17/09/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English summary of protocol
Background and study aims
Multiple Sclerosis (MS) is a progressive neurological disorder of the brain and spinal cord. It affects approximately 120,000 people in the UK and 2.5 million people globally. Most people with MS experience two stages of the disease: Early MS – Relapsing-Remitting MS (RRMS), which is partially reversible, and Late MS – Secondary Progressive MS (SPMS), which affects the majority of patients, usually after 10 to 15 years after diagnosis. SPMS results from progressive neuronal degeneration that causes accumulating and irreversible disability affecting walking, balance, manual function, vision, cognition, pain control, bladder and bowel function. The pathological process driving the accrual of disability in SPMS is not known at present. Immunomodulatory anti-inflammatory disease-modifying therapies (DMTs) are increasingly effective in reducing relapse frequency in RRMS, however, they have been unsuccessful in slowing disease progression in SPMS. This is the overwhelming conclusion from an analysis of 18 phase 3 trials (n=8500), of which 70% of the population had SPMS, all performed in the last 25 years. Siponimod was approved for use for SPMS in 2019 and is currently the only disease-modifying treatment (DMT) for SPMS. The aim of this study is to examine if repurposed Simvastatin (80mg) is a disease-modifying treatment for patients with progressing Secondary Progressive Multiple Sclerosis (SPMS).
Who can participate?
Adults aged 25 to 65 who have a confirmed diagnosis of MS.
What does the study involve?
The study is designed to test the effectiveness of repurposed simvastatin (80mg) in a phase 3 double blind, randomised, placebo controlled trial (1:1) in patients with secondary progressive MS (SPMS), to determine if the rate of disability progression can be slowed over a 3 year period.
Participants will be required to complete a minimum of 10 study appointments over a 36-month period. This will involve nine (9) visits to the hospital for study appointments and at least one (1) telephone call. At each study visit, participants will be asked to complete a number of study assessments including questionnaires and provide blood samples. Participants who meet all entry requirements are randomly allocated to receive either Simvastatin or Placebo. Participants will start off taking one (40mg) Simvastatin/Placebo tablet once daily at night for 1 month. The dose will increase after this and participants will take two (80mg) Simvastatin/Placebo tablets once daily at night for the next 35 months. Patients who have not had a confirmed disease progression event by 36 months will be invited to an optional series of additional 6-monthly visits to a maximum of 4.5 years from baseline (exact number dependent on duration until end of trial point).
What are the possible benefits and risks of participating?
The results generated from this trial may help to improve the treatment options of people with MS. In addition, taking part in this trial will mean regular review by an experienced neurologist regardless of the drug that participants are randomly allocated to receive. All medical procedures involve the risk of harm, but this is usually a low risk. In addition, there might be risks associated with this study that we do not yet know about.
Simvastatin is a well-tolerated drug and side effects are rare. However, in this trial, simvastatin will be given at a higher dose than is normally given to patients who use it to lower their cholesterol levels. Side effects can occasionally include muscle pain, tummy pain, blurred vision, dizziness and very rarely severe liver damage. Minor side effects include constipation, diarrhoea, fatigue and headaches. Participants are advised to inform their study doctor/nurse if they experience any of these side effects or have any concerns regarding their health at any point during the trial. Participants may be asked to attend the clinic for any additional visit(s) for further examination or tests.
There might be a risk of serious side effects when some medications are taken with the trial drug. Participants are advised to tell the study doctor about all medications they are taking before and during the trial. This includes other prescribed medicines, over the counter medicines, recreational drugs, herbal medicines or supplements. Grapefruit juice is known to interact unfavourably with simvastatin. Participants are advised not to drink grapefruit juice for the duration of the trial. The active study drug may pose unknown risks to a pregnant woman, an unborn baby, or a breastfeeding child. As such, pregnant women are not allowed to take part in this trial. Urine samples from female participants are tested at the screening visit (visit 1) to make sure they are not pregnant. All participants (male and female) are advised to use adequate contraception for the duration of the trial. All reasonable efforts are made to make this trial safe. Despite this, some risks might not be possible to predict.
Where is the study run from?
The study is being coordinated by the Comprehensive Clinical Trials Unit (UCL). Participants will have their study appointments at up to 30 participating Hospitals across the UK (England, Wales, Scotland, and Northern Ireland). The lead site is based at UCL (National Hospital for Neurology & Neurosurgery)
When is the study starting and how long is it expected to run for?
March 2017 to August 2024
Who is funding the study?
1. National Institute for Health Research (UK)
2. MS Society (UK)
3. National MS Society (USA)
Who is the main contact?
1. Mr James Blackstone
j.blackstone@ucl.ac.uk
2. Miss Rachel Merry
ms-stat2@ucl.ac.uk
3. Prof Jeremy Chataway
j.chataway@ucl.ac.uk
Contact information
Public
Comprehensive Clinical Trials Unit at UCL
Institute of Clinical Trials & Methodology
London
WC1V 6LJ
United Kingdom
 ORCID ID |
0000-0002-1503-7768 |
|---|---|
| Phone | +44 20 7907 4672 |
| ms-stat2@ucl.ac.uk |
Scientific
Institute of Neurology
University College London (UCL)
Queen Square
London
WC1N 3BG
United Kingdom
| ORCID ID |
0000-0001-7286-6901 |
|---|---|
| jeremy.chataway@uclh.nhs.uk |
Study information
| Study design | Randomized; Interventional; Design type: Treatment, Drug |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | A phase 3 randomised, double blind, clinical trial investigating the effectiveness of repurposed simvastatin compared to placebo, in secondary progressive multiple sclerosis, in slowing the progression of disability |
| Study acronym | MS-STAT2 |
| Study objectives | The hypothesis is that repurposed Simvastatin (80 mg) is a disease modifying treatment for patients with progressing Secondary Progressive Multiple Sclerosis (SPMS). |
| Ethics approval(s) | London - Westminster Research Ethics Committee, 09/10/2017, ref: 17/LO/1509 |
| Health condition(s) or problem(s) studied | Multiple sclerosis |
| Intervention | Participants are randomly allocated to one of two groups: Simvastatin (Active Treatment): Participants in this group start off taking one tablet. The number of tablets increases to two after a month. 1. One (1 = 40 mg) simvastatin tablet once daily at night for one month 2. Two (2 = 80 mg) simvastatin tablets once daily at night, for the next 35 months* Placebo: Participants in this group start off taking one tablet. The number of tablets increases to two after a month. 1. One (1) placebo tablet once daily at night for one month 2. Two (2) placebo tablets once daily at night, for the next 35 months* Participants are followed up on a six-month basis from baseline using the Expanded Disability Status Scale (EDSS) until the participant attends the last clinical appointment. Added 15/11/2023: *Extendable to up 54 months, for those participants taking part in the optional extension of IMP and follow-up, where they have not had confirmed disease progression by 36 months. |
| Intervention type | Other |
| Primary outcome measure | Time to initial disability progression between treatment arms is measured using the Expanded Disability Status Scale (EDSS) at baseline and then on a 6 month basis until last available EDSS score recorded at last attended clinic appointment/via telephone. |
| Secondary outcome measures | Current secondary outcome measures as of 15/11/2023: Current secondary outcome measures: 1. The clinical effect of neuroprotection based on clinician- and patient-reported outcome measures 2. The incremental cost and cost-effectiveness of simvastatin versus standard care for the trial period and for the lifetime horizon Clinician-reported outcome measures: 1. A modified Multiple Sclerosis Functional Composite (MSFC) outcome measure comprised of three components. The Symbol Digit Modalities Test (SDMT) will replace the Paced Auditory Serial Addition Test (PASAT), one of the three components in the standard MSFC. 1.1. Quantitative mobility and leg function measured using the 25-foot walk (T25FW) assessment at baseline, 6, 12, 18, 24, 30, 36 months and potentially at 42, 48 and 54 months for participants completing extension visits. 1.2. Fine motor coordination is measured using the 9 Hole peg test (9HPT) at baseline, 6, 12, 18, 24, 30, 36 months and potentially at 42, 48 and 54 months for participants completing extension visits. 1.3. Cognitive processing speed is measured using the Symbol digit modalities test (SDMT) at baseline, 12, 24 and 36 months. 2. Visual function is measured using the Sloan Low Contrast Visual Acuity (SLCVA) test at baseline, 12, 24 and 36 months. 3. Relapse assessment is measured by recording the number and severity experienced by participants at screening, baseline, 1, 3, 6, 12, 18, 24, 30, 36 months and potentially at 42, 48 and 54 months for participants completing extension visits. 4. The degree of disability in daily activities for patients with neurological disability is measured using the Modified Rankin Scale (mRS) at baseline, 12, 24 and 36 months. 5. Brief International Cognitive Assessment For Multiple Sclerosis (BICAMS), a composite cognitive assessment tool comprising of three components namely: 5.1. Cognitive processing speed is measured using the Symbol Digit Modalities Test (SDMT) at baseline, 12, 24 and 36 months. 5.2. Episodic verbal learning and memory measured using the California Verbal Learning Test-2(CVLT-II) at baseline and 36 months. 5.3. Immediate visual learning is measured using the Brief Visuospatial Memory Test - Revised (BVMT-R) at baseline and 36 months. Patient-reported outcome measures: 1. The impact of MS on people's lives is measured using the MS Impact Scale-29 v2 (MSIS-29v2) at baseline, 12, 24 and 36 months. 2. The impact of MS on the individual’s walking ability is measured using the MS Walking Scale-12 v2 (MSWS-12v2) at baseline, 12, 24 and 36 months. 3. The impact of fatigue on cognitive, physical and psychosocial function in patients with MS is measured using the Modified Fatigue Impact Scale – 21 (MFIS-21) at baseline, 12, 24 and 36 months. 4. The severity of physical and mental fatigue is measured using the Chalder Fatigue Questionnaire (CFQ) at baseline, 12, 24 and 36 months. 5. Quality-adjusted life years (QALY) is measured using the EQ-5D 5L questionnaire at baseline, 6, 12, 18, 24, 30, 36 months. 6. Information on service utilisation, income, accommodation, and other cost-related variables is collected using the Client Services Receipt Inventory (CSRI) questionnaire at baseline, 6, 12, 18, 24, 30, 36 months. Previous secondary outcome measures from 19/10/2018 to 15/11/2023: 1. The clinical effect of neuroprotection based on clinician- and patient-reported outcome measures 2. The incremental cost and cost-effectiveness of simvastatin versus standard care for the trial period and for the lifetime horizon Clinician-reported outcome measures: 1. A modified Multiple Sclerosis Functional Composite (MSFC) outcome measure comprised of three components. The Symbol Digit Modalities Test (SDMT) will replace the Paced Auditory Serial Addition Test (PASAT), one of the three components in the standard MSFC. 1.1. 25 foot walk (T25FW) 1.2. 9 Hole peg test (9HPT) 1.3. Symbol digit modalities test (SDMT) 2. Sloan Low Contrast Visual Acuity (SLCVA) 3. Relapse assessment – number and severity 4. Frontal Assessment Battery (FAB) 5. Modified Rankin Scale (mRS) 6. Brief International Cognitive Assessment For Multiple Sclerosis (BICAMS), a composite cognitive assessment tool comprising of the three components namely: 6.1. Symbol Digit Modalities Test (SDMT) 6.2. California Verbal Learning Test-2(CVLT-2) 6.3. Brief Visuospatial Memory Test- Revised (BVMT-R) Patient-reported outcome measures: 1. MS Impact Scale-29 v2 (MSIS-29v2) 2. MS Walking Scale-12 v2 (MSWS-12v2) 3. EQ-5D 5L Previous secondary outcome measures: 1. The clinical effect of neuroprotection based on clinician and patient reported outcome measures 2. The incremental cost and cost-effectiveness of simvastatin versus standard care for the trial period and for the lifetime horizon Clinician reported outcome measures: 1. A modified Multiple Sclerosis Functional Composite (MSFC) outcome measure comprised of three components. The Symbol Digit Modalities Test (SDMT) will replace the Paced Auditory Serial Addition Test (PASAT), one of the three components in the standard MSFC. 1.1. 25 foot walk (T25FW) 1.2. 9 Hole peg test (9HPT) 1.3. Symbol digit modalities test (SDMT) 2. Sloan Low Contrast Visual Acuity (SLCVA) 3. Relapse assessment – number and severity 4. Frontal Assessment Battery (FAB) 5. Modified Rankin Scale (mRS) 6. Brief International Cognitive Assessment For Multiple Sclerosis (BICAMS), a composite cognitive assessment tool comprising of the three components namely: 6.1. Symbol Digit Modalities Test (SDMT) 6.2. California Verbal Learning Test-2(CVLT-2) 6.3. Brief Visuospatial Memory Test- Revised (BVMT-R) Patient-reported outcome measures: 1. MS Impact Scale-29 v2 (MSIS-29v2) 2. MS Walking Scale-12 v2 (MSWS-12v2) 3. ABILHAND-56 4. EQ-5D 5L 5. SF-36 v2 |
| Overall study start date | 01/03/2017 |
| Completion date | 15/08/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 25 Years |
| Upper age limit | 65 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 1050 |
| Total final enrolment | 964 |
| Key inclusion criteria | Current participant inclusion criteria as of 24/05/2020: 1. Patients with a confirmed diagnosis of multiple sclerosis (MS) that have entered the secondary progressive stage. 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 1 point if EDSS score <6, or an increase of 0.5 points if EDSS score ≥6, or clinical documentation of increasing disability 2. EDSS 4.0 - 6.5 (inclusive) 3. Aged 25 to 65 years old 4. Patients must be able and willing to comply with the terms of this protocol 5. Written informed consent provided Previous participant inclusion criteria as of 19/10/2018: 1. Patients with a confirmed diagnosis of multiple sclerosis (MS) that have entered the secondary progressive stage. 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 1 point if on the Expanded Disability Status Scale (EDSS) score <6, or an increase of 0.5 point if EDSS score ≥6, or clinical documentation of increasing disability 2. EDSS 4.0 - 6.5 (inclusive) 3. Aged 25 to 65 years 4. Patients must be able and willing to comply with the terms of this protocol 5. Written informed consent provided Previous participant inclusion criteria: 1. Patients with a confirmed diagnosis of multiple sclerosis (MS) that have entered the secondary progressive stage at randomisation. 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 on the Expanded Disability Status Scale (EDSS), or clinical documentation of increasing disability 2. EDSS 4.0 - 6.5 (inclusive) 3. Aged 25 to 65 years old 4. Male or Female 5. Patients must be able and willing to comply with the terms of this protocol. 6. Written informed consent provided |
| Key exclusion criteria | Current participant exclusion criteria as of 15/11/2023: Current participant exclusion criteria: 1. Relapse within 3 months of baseline visit. Patients will be eligible where 3 months from the final day of the relapse, has elapsed by the date of the baseline visit 2. Patients that have been treated with steroids (intravenous and/or oral) due to MS relapse/progression within 3 months from the final day of relapse to the baseline visit. These patients may undergo a further screening visit once the 3-month window has expired and may be included if no steroid treatment has been administered in the intervening period (Note: Patients on steroids for another medical condition may be included in the trial provided the steroid prescription is not for MS relapse/progression) 3. Significant organ co-morbidity e.g. cardiac failure, renal failure, malignancy 4. Screening levels of alanine aminotransferase (ALT) / aspartate aminotransferase (AST) or creatine kinase (CK) ≥3 x upper limit of normal (ULN) 5. Current use of a statin; or any use within the last 6 months 6. Medications that interact unfavourably with simvastatin as outlined in the current summary of product characteristics (SmPC); including but not limited to CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, posaconazole, voriconazole, fluconazole, HIV protease inhibitors (e.g. nelfinavir), boceprevir, erythromycin, clrithromycin, telithromycin, telaprevir, nefazodone, fibrates (including fenofibrates), nicotinic acid (or products containing niacin), azole anti-fungal preparations, macrolide antibiotics, protease inhibitors, verapamil, amiodarone, amlodipine, gemfibrozil, ciclosporin, danazol, diltiazem, rifampicin, fusidic acid, elbasvir, grazoprevir, ticagrelor, daptomycin, grapefruit juice or alcohol abuse; 7. Primary progressive MS 8. Diabetes mellitus type 1 9. Uncontrolled hypothyroidism 10. Female participants who are pregnant or breastfeeding. Women of childbearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period, and up to 4 weeks after the last dose of study drug 11. Use of immunosuppressants (e.g. azathioprine, methotrexate, ciclosporine) or disease-modifying treatments (avonex, rebif, betaferon, glatiramer) within the previous 6 months 12. Use of mitoxantrone, natalizumab, alemtuzumab, daclizumab or other monoclonal antibody treatment, if treated within the last 12 months; 13. Use of fingolimod, dimethyl fumarate, teriflunomide, cladribine within the last 12 months 14. Use of other experimental disease-modifying treatment within the last 6 months 15. Commencement of fampridine ≤6 months from the day of randomisation 16. Concurrent participation in another clinical trial of an investigational medicinal product or medical device 17. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption Previous participant exclusion criteria from 24/05/2020 to 15/11/2023: 1. Relapse within 3 months of baseline visit 2. Patients that have been treated with steroids (intravenous and/or oral) due to MS relapse/progression within 3 months of baseline visit. These patients may undergo a further screening visit once the 3-month window has expired and may be included if no steroid treatment has been administered in the intervening period. Patients on steroids for another medical condition may be included in the trial provided. the steroid prescription is not for MS relapse/progression) 3. Significant organ co-morbidity e.g. cardiac failure, renal failure, malignancy 4. Screening levels of alanine aminotransferase (ALT) / aspartate aminotransferase (AST) or creatine kinase (CK) ≥3 x upper limit of normal (ULN) 5. Current use of a statin; or any use within the last 6 months 6. Medications that interact unfavourably with simvastatin as outlined in the current summary of product characteristics (SmPC); including but not limited to CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, posaconazole, voriconazole, fluconazole, HIV protease inhibitors (e.g. nelfinavir), boceprevir, erythromycin, clarithromycin, telithromycin, telaprevir, nefazodone, fibrates (including fenofibrates), nicotinic acid (or products containing niacin), azole anti-fungal preparations, macrolide antibiotics, protease inhibitors, verapamil, amiodarone, amlodipine, gemfibrozil, ciclosporin, danazol, diltiazem, rifampicin, fusidic acid, elbasvir, grazoprevir, grapefruit juice, or alcohol abuse 7. Primary progressive MS 8. Diabetes mellitus type 1 9. Uncontrolled hypothyroidism 10. Female participants who are pregnant or breastfeeding. Women of childbearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period, and up to 4 weeks after the last dose of study drug 11. Use of immunosuppressants (e.g. azathioprine, methotrexate, ciclosporine) or disease-modifying treatments (avonex, rebif, betaferon, or glatiramer) within the previous 6 months 12. Use of mitoxantrone, natalizumab, alemtuzumab, daclizumab or other monoclonal antibody treatment, if treated within the last 12 months 13. Use of fingolimod, dimethyl fumarate, teriflunomide, cladribine within the last 12 months 14. Use of other experimental disease-modifying treatment within the last 6 months 15. Commencement of fampridine ≤6 months from the day of randomisation 16. Concurrent participation in another clinical trial of an investigational medicinal product or medical device 17. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption Previous participant exclusion criteria as of 19/10/2018: 1. Relapse within 3 months of baseline visit 2. Patients that have been treated with steroids (intravenous and/or oral) due to MS relapse/progression within 3 months of baseline visit. These patients may undergo a further screening visit once the 3-month window has expired and may be included if no steroid treatment has been administered in the intervening period (Note: Patients on steroids for another medical condition may be included in the trial provided the steroid prescription is not for MS relapse/progression) 3. Significant organ co-morbidity e.g. cardiac failure, renal failure, malignancy 4. Screening levels of alanine aminotransferase (ALT) / aspartate aminotransferase (AST) or creatinine kinase (CK) > = 3x upper limit of normal (ULN) 5. Current use of a statin; or any use within the last 6 months 6. Medications that interact unfavourably with simvastatin as outlined in the current summary of product characteristics (SmPC); including but not limited to CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, posaconazole, voriconazole, fluconazole, HIV protease inhibitors (e.g. nelfinavir), boceprevir, erythromycin, clarithromycin, telithromycin, telaprevir, nefazodone, fibrates (including fenofibrates), nicotinic acid ( or products containing niacin), azole anti-fungal preparations, macrolide antibiotics, protease inhibitors, verapamil, amiodarone, amlodipine, gemfibrozil, ciclosporin, danazol, diltiazem, rifampicin, fusidic acid, grapefruit juice or alcohol abuse 7. Primary progressive MS 8. Diabetes Mellitus Type 1 9. Uncontrolled hypothyroidism 10. Female participants who are pregnant or breastfeeding. Women of childbearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period, and up to 4 weeks after the last dose of the study drug 11. Use of immunosuppressants (e.g. azathioprine, methotrexate, ciclosporine) or disease-modifying treatments (avonex, rebif, betaferon, glatiramer) within the previous 6 months 12. Use of mitoxantrone, natalizumab, alemtuzumab, daclizumab or other monoclonal antibody treatment, if treated within the last 12 months 13. Use of fingolimod, fumarate, teriflunomide within the last 12 months 14. Use of other experimental disease-modifying treatment within the last 6 months 15. Commencement of Fampridine <=6 month from day of randomisation 16. Concurrent participation in another clinical trial of an investigational medicinal product or medical device 17. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption Previous participant exclusion criteria: 1. Relapse within 3 months of baseline visit 2. Patients that have been treated with steroids (intravenous and/or oral) due to MS relapse/progression within 3 months of baseline visit. These patients may undergo a further screening visit once the 3-month window has expired and may be included if no steroid treatment has been administered in the intervening period (Note: Patients on steroids for another medical condition may be included in the trial provided the steroid prescription is not for MS relapse/progression) 3. Significant organ co-morbidity e.g. cardiac failure, renal failure, malignancy 4. Screening levels of alanine aminotransferase (ALT) / aspartate aminotransferase (AST) or creatinine kinase (CK) > = 3x upper limit of normal (ULN) 5. Current use of a statin; or any use within the last 6 months 6. Medications that interact unfavourably with simvastatin as outlined in the current summary of product characteristics (SmPC); including but not limited to CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, posaconazole, voriconazole, fluconazole, HIV protease inhibitors (e.g. nelfinavir), boceprevir, erythromycin, clarithromycin, telithromycin, telaprevir, nefazodone, fibrates (including fenofibrates), nicotinic acid ( or products containing niacin), azole anti-fungal preparations, macrolide antibiotics, protease inhibitors, verapamil, amiodarone, amlodipine, gemfibrozil, ciclosporin, danazol , diltiazem, rifampicin , fusidic acid, grapefruit juice or alcohol abuse 7. Primary progressive MS 8. Diabetes Mellitus Type 1 9. Uncontrolled hypothyroidism 10. Female participants who are pregnant or breastfeeding. Women of childbearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period, and up to 4 weeks after the last dose of study drug 11. Use of immunosuppressants (e.g. azathioprine, methotrexate, ciclosporine) or disease-modifying treatments (avonex, rebif, betaferon, glatiramer) within the previous 6 months 12. Use of mitoxantrone, natalizumab, alemtuzumab, daclizumab or other monoclonal antibody treatment, if treated within the last 12 months 13. Use of fingolimod, fumarate, teriflunomide within the last 12 months 14. Use of other experimental disease-modifying treatment within the last 6 months 15. Commencement of Fampridine <=6 month from day of randomisation 16. Concurrent participation in another clinical trial of an investigational medicinal product or medical device |
| Date of first enrolment | 28/03/2018 |
| Date of final enrolment | 30/09/2021 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
London
WC1N 3BG
United Kingdom
Sponsor information
University/education
Gower Street, Bloomsbury
London
WC1E 6BT
England
United Kingdom
"ROR" |
https://ror.org/02jx3x895 |
|---|
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
No information available
No information available
Results and Publications
| Intention to publish date | 30/11/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Trial results will be published in a high-impact peer-reviewed journal. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available. Patient-identifiable data will not be published. The anonymity of all participants will be maintained at all times and results published in aggregate form. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol article | 16/09/2024 | 17/09/2024 | Yes | No |
Editorial Notes
17/09/2024: Publication reference added.
21/08/2024: The following changes have been made:
1. IRAS number added.
2. The overall study end date was changed from 31/08/2024 to 15/08/2024.
15/11/2023: The following changes were made to the study record:
1. The interventions, secondary outcome measures, exclusion criteria were updated.
2. The recruitment end date was changed from 30/11/2020 to 30/09/2021.
3. MS Society (UK), and National MS Society (USA) were added to the funders.
4. The intention to publish date was changed from 31/08/2023 to 30/11/2024.
5. Ireland was removed from the countries of recruitment.
6. Total final enrolment added.
20/09/2021: Internal review.
24/05/2020: The following changes have been made:
1. The recruitment end date has been changed from 30/11/2019 to 30/11/2020.
2. The overall trial end date has been changed from 31/08/2023 to 31/08/2024.
3. The participant inclusion criteria have been updated.
4. The participant exclusion criteria have been updated.
5. The target number of participants and the total target enrolment number has been changed from "1180" to "1050".
6. The plain English summary has been updated to reflect the changes above and to include additional trial contact details.
21/06/2019: Added ClinicalTrials.gov number.
03/04/2019: The condition has been changed from "Specialty: Neurological disorders, Primary sub-specialty: Multiple Sclerosis; UKCRC code/ Disease: Neurological/ Demyelinating diseases of the central nervous system" to "Multiple Sclerosis" following a request from the NIHR.
19/10/2018: The following changes have been made:
1. The secondary outcome measures have been changed.
2. The participant inclusion criteria have been changed.
3. The participant exclusion criteria have been changed.
4. The recruitment start date has been changed from 01/01/2018 to 28/03/2018.
17/10/2018: The public contact has been changed from Dr Martha Bajwa Joseph to Liz Deane.
