Secondary Progressive Multiple SclerosisPhase 2MS-SMARTNCT01910259
MS-SMART: Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial
A Phase 2 study testing Amiloride, Riluzole and Fluoxetine in people with Secondary Progressive Multiple Sclerosis, run by University College, London at 13 sites in United Kingdom.
Trial summary
Multiple sclerosis (MS) is a disabling and progressive neurological disease that affects approximately 100,000 people in the UK. Many patients with MS experience two phases of disease; early MS (also called relapsing remitting MS, RRMS) and late MS (also called secondary progressive MS (SPMS). Read more about this study
- Who is it for?
- Ages 25 to 65 years
- Conditions the study is for
- Secondary Progressive Multiple Sclerosis
- What is being tested?
- Amiloride, Riluzole and Fluoxetine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 445 participants
- Where
- 13 sitesUnited Kingdom
- Study dates
- 18 Dec 2014to 4 Jul 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 33Show fewer
- 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
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United Kingdom13 sites
Anne Rowling Regenerative Neurology Clinic, Royal Infirmary of Edinburgh
Edinburgh, EH16 4SA
Gartnavel Royal Hospital, 1055 Great Western Road
Glasgow, G12 OXH
Brighton and Sussex University Hospitals
Haywards Heath, RH16 4EX
St James's University Hospital
Leeds, LS9 7TF
The Walton Centre
Liverpool, L9 7LJ
The National hospital for Neurology and Neurosurgery, University College London
London, WC1N 3BG
The Royal Victoria Infirmary
Newcastle, NE1 4LP
Queens Medical Centre
Nottingham, NG7 2UH
John Radcliffe Hospital, Oxford University Hospitals NHS Trust
Oxford, OX3 9DU
Derriford Hospital
Plymouth, PL6 8DH
Royal Hallamshire Hospital
Sheffield, S10 2JF
University Hospital of North Staffordshire
Stoke-on-Trent, ST4 7LN
Royal Cornwall Hospital
Truro, TR1 3LJ
About this study
Official 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.
Multiple sclerosis (MS) is a disabling and progressive neurological disease that affects approximately 100,000 people in the UK. Many patients with MS experience two phases of disease; early MS (also called relapsing remitting MS, RRMS) and late MS (also called secondary progressive MS (SPMS). Early MS is due to inflammation of the nerves and the insulation (called myelin) that surrounds the nerves. Early MS is often characterised by periods of "attacks" interspersed with periods of "remission" with no or low disease symptoms. Late or progressive MS, which affects the majority of patients and typically emerges after 10-15 years of disease, results from actual nerve death (also called neurodegeneration). The progressive stage of disease results not in individual attacks but slow, cumulative and irreversible disability affecting walking, balance, vision, cognition, pain control, bladder and bowel function. Critically, and unlike early disease, there is no proven treatment for the late stage of MS. This is therefore an urgent and major unmet health need. MS-SMART directly addresses this need and will evaluate in this clinical trial three drugs (fluoxetine, riluzole or amiloride), all of which have shown some promise in MS, and in particular in SPMS. The trial is randomised and blinded. Randomisation means patients can get any one of the three active drugs or the inactive placebo/dummy; blinded means that neither patients nor the doctors will know which drug or placebo patients are receiving. Randomisation and blinding are standard approaches in clinical trials to ensure unbiased testing of drugs. All patients in MS-SMART will have periodic MRI (magnetic resonance imaging) brain scans and after 96 weeks these will be analysed. We will then compare the scans of each drug to the placebo or dummy to see if any of the drugs slow the rate of brain shrinkage that normally occurs in SPMS. This measured change in brain size is the primary (major) outcome of MS-SMART.
Read the detailed description
MS-SMART will test the efficacy and mechanism of action of three repurposed drugs (fluoxetine, riluzole and amiloride). All three drugs are in human use and have a good safety record. Critically for the purpose of MS-SMART they all have shown promise in early phase human MS clinical trials and target one or more of the pivotal neurodegenerative causing pathways implicated in SPMS. This is a Type B trial, as the IMPs are all in human use, have a good safety profile but are not currently used for this patient population.
The major need for patients with established and progressive MS is neuroprotective or disease modifying treatments that will slow or even stop disease progression. This study will evaluate three highly promising putative neuroprotective drugs as well as comprehensively address several of the current knowledge gaps related to the understanding of neuroprotection and neurodegeneration in SPMS through MRI and CSF examination.
MS-SMART is a multicentre, multi-arm, double blind, placebo-controlled phase IIb randomised controlled trial. A total of 440 patients with SPMS, with an entry criteria of an EDSS score of 4.0-6.5 will be equally randomised to receive placebo or one of the three active agents (fluoxetine 20mg bd, amiloride 5mg bd or riluzole 50mg bd). Patients will be followed up for 96 weeks with outcome-data collected after 0, 24, 48 and 96 weeks. That is, the duration of the trial for a trial participant is 96 weeks (a telephone assessment at week 100, 4 weeks post completion will be conducted). This is standard practice for phase II trials in SPMS.
- Conditions
- Secondary Progressive Multiple Sclerosis
- Being tested
- Amiloride, Riluzole, Fluoxetine, Placebo
- Keywords
- Secondary Progressive Multiple Sclerosis, Neuroprotective, Repurposed drugs, Brain atrophy, Percentage Brain Volume Change, Magnetic Resonance Imaging, Optical Coherence Tomography, Cerebrospinal fluid, Amiloride, Riluzole, Double blind, Placebo, Fluoxetine
- Medical subject headings
- Multiple Sclerosis, Chronic Progressive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmilorideDrug
Comparison with placebo
RiluzoleDrug
Comparison with placebo
FluoxetineDrug
Comparison with placebo
PlaceboDrug
Placebo comparator
| Study group | Role | What they receive |
|---|---|---|
| Amiloride | Experimental | Amiloride 5 mg twice per day (5 mg once per day for first 4 weeks) for 96 weeks Receives: Drug: Amiloride |
| Riluzole | Experimental | Riluzole 50 mg twice per day (50 mg once per day for first 4 weeks) for 96 weeks Receives: Drug: Riluzole |
| Fluoxetine | Experimental | Fluoxetine 20 mg twice per day (20 mg once per day for first 4 weeks) for 96 weeks Receives: Drug: Fluoxetine |
| Placebo | Placebo comparator | Matched placebo 1 capsule twice per day (1 capsule a day for first 4 weeks) for 96 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
MRI-derived Percentage Brain Volume Change (PBVC).
To establish whether a drug, from a panel of 3 leading candidate neuroprotective drugs, slows the rate of brain volume loss in SPMS over 96 weeks using MRI-derived percentage brain volume change (PBVC).
Measured: 2 years
Secondary outcomes (5)
Multi-arm trial strategy assessment
To establish that a multi-arm trial strategy is an efficient way of screening drugs in SPMS and can become the template for future work.
Measured: 2 years
Count of new and enlarging T2 lesions
To explore any anti-inflammatory drug activity using the count of new and enlarging T2 lesions.
Measured: 2 years
Pseudo-atrophy
Examining for evidence of pseudo-atrophy (to ensure reliability of the primary outcome measure).
Measured: 6 months
Clinical measure of neuroprotection
To examine the clinical effect of neuroprotection as measured by clinician - EDSS, MSFC, SDMT, SLCVA, relapse rate and patient reported outcome measures - MSIS29 v2, MSWS v2, Pain - NPRS and BPI and Fatigue - NFI.
Measured: 2 years
Health economics
To collect basic health economic data (EQ-5D) to inform future phase III trials.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2013 (estimated)
- Study start18 Dec 2014
- Primary completion14 Jun 2018
- Study completion4 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Secondary Progressive Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 445 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Research Council, National Institute for Health Research, United Kingdom, National Multiple Sclerosis Society, University of Edinburgh, Queen Mary University of London, Keele University, University of Sheffield, University of Leeds, University of Warwick
- Responsible party
- Sponsor
- Investigators
- Jeremy Chataway, Principal investigator, University College, LondonSiddharthan Chandran, Principal investigator, University of Edinburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01910259
- Sponsor's protocol ID
- 12/0219
- Acronym
- MS-SMART
- Status last verified
- Mar 2020
- First submitted
- 19 Jul 2013
- Last updated
- 26 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
John N, Li Y, De Angelis F, Stutters J, Prados Carrasco F, Eshaghi A, Doshi A, Calvi A, Williams T, Plantone D, Phan T, Barkhof F, Chataway J; MS-SMART Investigators; Ourselin S, Braisher M, Beyene T, Bassan V, Zapata A, Chandran S, Connick P, Lyle D, Cameron J, Mollison D, Colville S, Dhillon B, Ross M, Cranswick G, Walker A, Smith L, Giovannoni G, Gnanapavan S, Nicholas R, Rashid W, Aram J, Ford H, Pavitt SH, Overell J, Young C, Arndt H, Duddy M, Guadagno J, Evangelou N, Craner M, Palace J, Hobart J, Sharrack B, Paling D, Hawkins C, Kalra S, McLean B, Stallard N, Bastow R. Brain reserve and physical disability in secondary progressive multiple sclerosis. BMJ Neurol Open. 2024 Sep 7;6(2):e000670. doi: 10.1136/bmjno-2024-000670. eCollection 2024.
PubMed 39262426Williams T, Alexander S, Blackstone J, De Angelis F, John N, Doshi A, Beveridge J, Braisher M, Gray E, Chataway J; MS-SMART and MS-STAT2 Investigators. Optimising recruitment in clinical trials for progressive multiple sclerosis: observational analysis from the MS-SMART and MS-STAT2 randomised controlled trials. Trials. 2022 Aug 9;23(1):644. doi: 10.1186/s13063-022-06588-z.
PubMed 35945550Chataway J, De Angelis F, Connick P, Parker RA, Plantone D, Doshi A, John N, Stutters J, MacManus D, Prados Carrasco F, Barkhof F, Ourselin S, Braisher M, Ross M, Cranswick G, Pavitt SH, Giovannoni G, Gandini Wheeler-Kingshott CA, Hawkins C, Sharrack B, Bastow R, Weir CJ, Stallard N, Chandran S; MS-SMART Investigators. Efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis (MS-SMART): a phase 2b, multiarm, double-blind, randomised placebo-controlled trial. Lancet Neurol. 2020 Mar;19(3):214-225. doi: 10.1016/S1474-4422(19)30485-5. Epub 2020 Jan 22.
PubMed 31981516Connick P, De Angelis F, Parker RA, Plantone D, Doshi A, John N, Stutters J, MacManus D, Prados Carrasco F, Barkhof F, Ourselin S, Braisher M, Ross M, Cranswick G, Pavitt SH, Giovannoni G, Gandini Wheeler-Kingshott CA, Hawkins C, Sharrack B, Bastow R, Weir CJ, Stallard N, Chandran S, Chataway J; UK Multiple Sclerosis Society Clinical Trials Network. Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART): a multiarm phase IIb randomised, double-blind, placebo-controlled clinical trial comparing the efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis. BMJ Open. 2018 Aug 30;8(8):e021944. doi: 10.1136/bmjopen-2018-021944.
PubMed 30166303
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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.
- ClinicalTrials.gov ID
- NCT01910259
- Acronym / sponsor ID
- MS-SMART / 12/0219
- Conditions
- Secondary Progressive Multiple Sclerosis
- Keywords
- Secondary Progressive Multiple Sclerosis, Neuroprotective, Repurposed drugs, Brain atrophy, Percentage Brain Volume Change, Magnetic Resonance Imaging, Optical Coherence Tomography, Cerebrospinal fluid
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 445 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- Medical Research Council, National Institute for Health Research, United Kingdom, National Multiple Sclerosis Society, University of Edinburgh, Queen Mary University of London, Keele University, University of Sheffield, University of Leeds, University of Warwick
- Study start
- 18 Dec 2014 (actual)
- Primary completion
- 14 Jun 2018 (actual)
- Study completion
- 4 Jul 2018 (actual)
- First posted
- 29 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Multiple sclerosis (MS) is a disabling and progressive neurological disease that affects approximately 100,000 people in the UK. Many patients with MS experience two phases of disease; early MS (also called relapsing remitting MS, RRMS) and late MS (also called secondary progressive MS (SPMS). Early MS is due to inflammation of the nerves and the insulation (called myelin) that surrounds the nerves. Early MS is often characterised by periods of "attacks" interspersed with periods of "remission" with no or low disease symptoms. Late or progressive MS, which affects the majority of patients and typically emerges after 10-15 years of disease, results from actual nerve death (also called neurodegeneration). The progressive stage of disease results not in individual attacks but slow, cumulative and irreversible disability affecting walking, balance, vision, cognition, pain control, bladder and bowel function. Critically, and unlike early disease, there is no proven treatment for the late stage of MS. This is therefore an urgent and major unmet health need. MS-SMART directly addresses this need and will evaluate in this clinical trial three drugs (fluoxetine, riluzole or amiloride), all of which have shown some promise in MS, and in particular in SPMS. The trial is randomised and blinded. Randomisation means patients can get any one of the three active drugs or the inactive placebo/dummy; blinded means that neither patients nor the doctors will know which drug or placebo patients are receiving. Randomisation and blinding are standard approaches in clinical trials to ensure unbiased testing of drugs. All patients in MS-SMART will have periodic MRI (magnetic resonance imaging) brain scans and after 96 weeks these will be analysed. We will then compare the scans of each drug to the placebo or dummy to see if any of the drugs slow the rate of brain shrinkage that normally occurs in SPMS. This measured change in brain size is the primary (major) outcome of MS-SMART.
Detailed description
MS-SMART will test the efficacy and mechanism of action of three repurposed drugs (fluoxetine, riluzole and amiloride). All three drugs are in human use and have a good safety record. Critically for the purpose of MS-SMART they all have shown promise in early phase human MS clinical trials and target one or more of the pivotal neurodegenerative causing pathways implicated in SPMS. This is a Type B trial, as the IMPs are all in human use, have a good safety profile but are not currently used for this patient population.
The major need for patients with established and progressive MS is neuroprotective or disease modifying treatments that will slow or even stop disease progression. This study will evaluate three highly promising putative neuroprotective drugs as well as comprehensively address several of the current knowledge gaps related to the understanding of neuroprotection and neurodegeneration in SPMS through MRI and CSF examination.
MS-SMART is a multicentre, multi-arm, double blind, placebo-controlled phase IIb randomised controlled trial. A total of 440 patients with SPMS, with an entry criteria of an EDSS score of 4.0-6.5 will be equally randomised to receive placebo or one of the three active agents (fluoxetine 20mg bd, amiloride 5mg bd or riluzole 50mg bd). Patients will be followed up for 96 weeks with outcome-data collected after 0, 24, 48 and 96 weeks. That is, the duration of the trial for a trial participant is 96 weeks (a telephone assessment at week 100, 4 weeks post completion will be conducted). This is standard practice for phase II trials in SPMS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Amiloride | Experimental | Drug: AmilorideAmiloride 5 mg twice per day (5 mg once per day for first 4 weeks) for 96 weeks |
| Riluzole | Experimental | Drug: RiluzoleRiluzole 50 mg twice per day (50 mg once per day for first 4 weeks) for 96 weeks |
| Fluoxetine | Experimental | Drug: FluoxetineFluoxetine 20 mg twice per day (20 mg once per day for first 4 weeks) for 96 weeks |
| Placebo | Placebo comparator | Drug: PlaceboMatched placebo 1 capsule twice per day (1 capsule a day for first 4 weeks) for 96 weeks |
Who may qualify
- Ages
- 25 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (33 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AmilorideComparison with placebo | Drug | Amiloride |
| RiluzoleComparison with placebo | Drug | Riluzole |
| FluoxetineComparison with placebo | Drug | Fluoxetine |
| PlaceboPlacebo comparator | Drug | Placebo |
Primary outcome
MRI-derived Percentage Brain Volume Change (PBVC).
Time frame: 2 years
To establish whether a drug, from a panel of 3 leading candidate neuroprotective drugs, slows the rate of brain volume loss in SPMS over 96 weeks using MRI-derived percentage brain volume change (PBVC).
5 secondary outcomes
Multi-arm trial strategy assessment
Time frame: 2 years
Count of new and enlarging T2 lesions
Time frame: 2 years
Pseudo-atrophy
Time frame: 6 months
Clinical measure of neuroprotection
Time frame: 2 years
Health economics
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2020.
- Derived from this study: PubMed 39262426John N, Li Y, De Angelis F, Stutters J, Prados Carrasco F, Eshaghi A, Doshi A, Calvi A, Williams T, Plantone D, Phan T, Barkhof F, Chataway J; MS-SMART Investigators; Ourselin S, Braisher M, Beyene T, Bassan V, Zapata A, Chandran S, Connick P, Lyle D, Cameron J, Mollison D, Colville S, Dhillon B, Ross M, Cranswick G, Walker A, Smith L, Giovannoni G, Gnanapavan S, Nicholas R, Rashid W, Aram J, Ford H, Pavitt SH, Overell J, Young C, Arndt H, Duddy M, Guadagno J, Evangelou N, Craner M, Palace J, Hobart J, Sharrack B, Paling D, Hawkins C, Kalra S, McLean B, Stallard N, Bastow R. Brain reserve and physical disability in secondary progressive multiple sclerosis. BMJ Neurol Open. 2024 Sep 7;6(2):e000670. doi: 10.1136/bmjno-2024-000670. eCollection 2024.
- Derived from this study: PubMed 35945550Williams T, Alexander S, Blackstone J, De Angelis F, John N, Doshi A, Beveridge J, Braisher M, Gray E, Chataway J; MS-SMART and MS-STAT2 Investigators. Optimising recruitment in clinical trials for progressive multiple sclerosis: observational analysis from the MS-SMART and MS-STAT2 randomised controlled trials. Trials. 2022 Aug 9;23(1):644. doi: 10.1186/s13063-022-06588-z.
- Derived from this study: PubMed 31981516Chataway J, De Angelis F, Connick P, Parker RA, Plantone D, Doshi A, John N, Stutters J, MacManus D, Prados Carrasco F, Barkhof F, Ourselin S, Braisher M, Ross M, Cranswick G, Pavitt SH, Giovannoni G, Gandini Wheeler-Kingshott CA, Hawkins C, Sharrack B, Bastow R, Weir CJ, Stallard N, Chandran S; MS-SMART Investigators. Efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis (MS-SMART): a phase 2b, multiarm, double-blind, randomised placebo-controlled trial. Lancet Neurol. 2020 Mar;19(3):214-225. doi: 10.1016/S1474-4422(19)30485-5. Epub 2020 Jan 22.
- Derived from this study: PubMed 30166303Connick P, De Angelis F, Parker RA, Plantone D, Doshi A, John N, Stutters J, MacManus D, Prados Carrasco F, Barkhof F, Ourselin S, Braisher M, Ross M, Cranswick G, Pavitt SH, Giovannoni G, Gandini Wheeler-Kingshott CA, Hawkins C, Sharrack B, Bastow R, Weir CJ, Stallard N, Chandran S, Chataway J; UK Multiple Sclerosis Society Clinical Trials Network. Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART): a multiarm phase IIb randomised, double-blind, placebo-controlled clinical trial comparing the efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis. BMJ Open. 2018 Aug 30;8(8):e021944. doi: 10.1136/bmjopen-2018-021944.
- Trial websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeremy Chataway principal investigator
University College, London
Siddharthan Chandran principal investigator
University of Edinburgh
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Amiloride, Riluzole and Fluoxetine in people with Secondary Progressive Multiple Sclerosis, run by University College, London at 13 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MRI-derived Percentage Brain Volume Change (PBVC). (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01910259, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2020; AzTrials last refreshed its copy on 28 Oct 2026.