8 results on '"Bastow, Roger"'
Search Results
2. Remote handling assessment of attachment concepts for DEMO blanket segments
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Iglesias, Daniel, Bastow, Roger, Cooper, Dave, Crowe, Robert, Middleton-Gear, Dave, Sibois, Romain, Carloni, Dario, Vizvary, Zsolt, Crofts, Oliver, Harman, Jon, and Loving, Antony
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- 2015
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3. Evolving the JET virtual reality system for delivering the JET EP2 shutdown remote handling tasks
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Williams, Adrian, Sanders, Stephen, Weder, Gerard, Bastow, Roger, Allan, Peter, and Hazel, Stuart
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- 2011
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4. Amiloride, fluoxetine or riluzole to reduce brain volume loss in secondary progressive multiple sclerosis: the MS-SMART four-arm RCT
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De Angelis, Floriana, primary, Connick, Peter, additional, Parker, Richard A, additional, Plantone, Domenico, additional, Doshi, Anisha, additional, John, Nevin, additional, Stutters, Jonathan, additional, MacManus, David, additional, Prados, Ferran, additional, Marshall, Ian, additional, Solanky, Bhavana, additional, Samson, Rebecca S, additional, Barkhof, Frederik, additional, Ourselin, Sebastien, additional, Braisher, Marie, additional, Ross, Moira, additional, Cranswick, Gina, additional, Pavitt, Sue H, additional, Gnanapavan, Sharmilee, additional, Giovannoni, Gavin, additional, Wheeler-Kingshott, Claudia AM Gandini, additional, Hawkins, Clive, additional, Sharrack, Basil, additional, Bastow, Roger, additional, Weir, Christopher J, additional, Stallard, Nigel, additional, Chandran, Siddharthan, additional, and Chataway, Jeremy, additional
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- 2020
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5. 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
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Connick, Peter, primary, De Angelis, Floriana, additional, Parker, Richard A, additional, Plantone, Domenico, additional, Doshi, Anisha, additional, John, Nevin, additional, Stutters, Jonathan, additional, MacManus, David, additional, Prados Carrasco, Ferran, additional, Barkhof, Frederik, additional, Ourselin, Sebastien, additional, Braisher, Marie, additional, Ross, Moira, additional, Cranswick, Gina, additional, Pavitt, Sue H, additional, Giovannoni, Gavin, additional, Gandini Wheeler-Kingshott, Claudia Angela, additional, Hawkins, Clive, additional, Sharrack, Basil, additional, Bastow, Roger, additional, Weir, Christopher J, additional, Stallard, Nigel, additional, Chandran, Siddharthan, additional, and Chataway, Jeremy, additional
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- 2018
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6. Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MSSMART): a multiarm phase IIb randomised, double-blind, placebo-controlled clinical trial comparing the efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis
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Connick, Peter, De Angelis, Floriana, Parker, Richard A., Plantone, Domenico, Doshi, Anisha, John, Nevin, Stutters, Jonathan, MacManus, David, Carrasco, Ferran Prados, Barkhof, Frederik, Ourselin, Sebastien, Braisher, Marie, Ross, Moira, Cranswick, Gina, Pavitt, Sue H., Giovannoni, Gavin, Wheeler-Kingshott, Claudia Angela Gandini, Hawkins, Clive, Sharrack, Basil, and Bastow, Roger
- Abstract
Introduction The major unmet need in multiple sclerosis (MS) is for neuroprotective therapies that can slow (or ideally stop) the rate of disease progression. The UK MS Society Clinical Trials Network (CTN) was initiated in 2007 with the purpose of developing a national, efficient, multiarm trial of repurposed drugs. Key underpinning work was commissioned by the CTN to inform the design, outcome selection and drug choice including animal models and a systematic review. This identified seven leading oral agents for repurposing as neuroprotective therapies in secondary progressive MS (SPMS). The purpose of the Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART) will be to evaluate the neuroprotective efficacy of three of these drugs, selected with distinct mechanistic actions and previous evidence of likely efficacy, against a common placebo arm. The interventions chosen were: amiloride (acid-sensing ion channel antagonist); fluoxetine (selective serotonin reuptake inhibitor) and riluzole (glutamate antagonist). Methods and analysis Patients with progressing SPMS will be randomised 1:1:1:1 to amiloride, fluoxetine, riluzole or matched placebo and followed for 96 weeks. The primary outcome will be the percentage brain volume change (PBVC) between baseline and 96 weeks, derived from structural MR brain imaging data using the Structural Image Evaluation, using Normalisation, of Atrophy method. With a sample size of 90 per arm, this will give 90% power to detect a 40% reduction in PBVC in any active arm compared with placebo and 80% power to detect a 35% reduction (analysing by analysis of covariance and with adjustment for multiple comparisons of three 1.67% two-sided tests), giving a 5% overall two-sided significance level. MS-SMART is not powered to detect differences between the three active treatment arms. Allowing for a 20% dropout rate, 110 patients per arm will be randomised. The study will take place at Neuroscience centres in England and Scotland. Ethics and dissemination MS-SMART was approved by the Scotland A Research Ethics Committee on 13 January 2013 (REC reference: 13/SS/0007). Results of the study will be submitted for publication in a peer-reviewed journal. [ABSTRACT FROM AUTHOR]
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- 2018
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7. Brain reserve and physical disability in secondary progressive multiple sclerosis.
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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, 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, and Bastow R
- Abstract
Background: The brain reserve hypothesis posits that larger maximal lifetime brain growth (MLBG) may confer protection against physical disability in multiple sclerosis (MS). Larger MLBG as a proxy for brain reserve, has been associated with reduced progression of physical disability in patients with early MS; however, it is unknown whether this association remains once in the secondary progressive phase of MS (SPMS). Our aim was to assess whether larger MLBG is associated with decreased physical disability progression in SPMS., Methods: We conducted a post hoc analysis of participants in the MS-Secondary Progressive Multi-Arm Randomisation Trial (NCT01910259), a multicentre randomised placebo-controlled trial of the neuroprotective potential of three agents in SPMS. Physical disability was measured by Expanded Disability Status Scale (EDSS), 9-hole peg test (9HPT) and 25-foot timed walk test (T25FW) at baseline, 48 and 96 weeks. MLBG was estimated by baseline intracranial volume (ICV). Multivariable time-varying Cox regression models were used to investigate the association between MLBG and physical disability progression., Results: 383 participants (mean age 54.5 years, 298 female) were followed up over 96 weeks. Median baseline EDSS was 6.0 (range 4.0-6.5). Adjusted for covariates, larger MLBG was associated with a reduced risk of EDSS progression (HR 0.84,95% CI:0.72 to 0.99;p=0.04). MLBG was not independently associated with time to progression as measured by 9HPT or T25FW., Conclusion: Larger MLBG is independently associated with physical disability progression over 96 weeks as measured by EDSS in SPMS. This suggests that MLBG as a proxy for brain reserve may continue to confer protection against disability when in the secondary progression phase of MS., Trail Registration Number: NCT01910259., Competing Interests: NJ is a local principal investigator on commercial MS studies funded by Novartis, Roche and Sanofi. He has received speakers honoraria from Merck and congress sponsorship covering registration and travel from Novartis. FB serves on the editorial boards of Brain, European Radiology, Journal of Neurology, Neurosurgery & Psychiatry, Neurology, Multiple Sclerosis and Neuroradiology, and serves as consultant for Bayer Schering Pharma, Sanofi-Aventis, Biogen-Idec, TEVA Pharmaceuticals, Genzyme, Merck-Serono, Novartis, Roche, Synthon, Jansen Research and Lundbeck. CAGW-K has received research grants (PI and co-applicant) from Spinal Research, Craig H. Neilsen Foundation, EPSRC, Wings for Life, UK MS Society, Horizon 2020, NIHR/MRC, MRC and is a shareholder of Queen Square Analytics. In the last 3 years, JC has received support from the Efficacy and Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership and the Health Technology Assessment (HTA) Programme (NIHR), the UK MS Society, the US National MS Society and the Rosetrees Trust. He is supported in part by the National Institute for Health Research, University College London Hospitals, Biomedical Research Centre, London, UK. He has been a local principal investigator for a trial in MS funded by the Canadian MS Society. A local principal investigator for commercial trials funded by: Actelion, Biogen, Novartis and Roche; has received an investigator grant from Novartis; and has taken part in advisory boards/consultancy for Azadyne, Biogen, Celgene, Janssen, MedDay, Merck, NervGen, Novartis and Roche., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)
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- 2024
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8. Amiloride, fluoxetine or riluzole to reduce brain volume loss in secondary progressive multiple sclerosis: the MS-SMART four-arm RCT
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De Angelis F, Connick P, Parker RA, Plantone D, Doshi A, John N, Stutters J, MacManus D, Prados F, Marshall I, Solanky B, Samson RS, Barkhof F, Ourselin S, Braisher M, Ross M, Cranswick G, Pavitt SH, Gnanapavan S, Giovannoni G, Wheeler-Kingshott CAMG, Hawkins C, Sharrack B, Bastow R, Weir CJ, Stallard N, Chandran S, and Chataway J
- Abstract
Background: Neuroprotective drugs are needed to slow or prevent neurodegeneration and disability accrual in secondary progressive multiple sclerosis. Amiloride, fluoxetine and riluzole are repurposed drugs with potential neuroprotective effects., Objectives: To assess whether or not amiloride, fluoxetine and riluzole can reduce the rate of brain volume loss in people with secondary progressive multiple sclerosis over 96 weeks. The secondary objectives that were assessed were feasibility of a multiarm trial design approach, evaluation of anti-inflammatory effects, clinician- and patient-reported efficacy and three mechanistic substudies., Design: A multicentre, multiarm, randomised, double-blind, placebo-controlled, parallel-group Phase IIb trial with follow-up at 4, 8, 12, 24, 36, 48, 72 and 96 weeks. Patients, investigators (including magnetic resonance imaging analysts), and treating and independent assessing neurologists were blinded to the treatment allocation. The target sample size was 440 patients., Setting: Thirteen UK clinical neuroscience centres., Participants: Participants were aged 25–65 years, had secondary progressive multiple sclerosis with evidence of disease progression independent of relapses in the previous 2 years, and had an Expanded Disability Status Scale score of 4.0–6.5. Patients were ineligible if they could not have a magnetic resonance imaging scan; had a relapse or steroids in the previous 3 months; or had epilepsy, depression, bipolar disorder, glaucoma, bleeding disorders or significant organ comorbidities. Exclusion criteria were concurrent disease-modified treatments, immunosuppressants or selective serotonin reuptake inhibitors., Interventions: Participants received amiloride (5 mg), fluoxetine (20 mg), riluzole (50 mg) or placebo (randomised 1 : 1 : 1 : 1) twice daily., Main Outcome Measures: The primary end point was magnetic resonance imaging-derived percentage brain volume change at 96 weeks. Secondary end points were new/enlarging T2 lesions, pseudoatrophy, and clinician- and patient-reported measures (including the Expanded Disability Status Scale, Multiple Sclerosis Functional Composite, Symbol Digit Modalities Test, low-contrast letter visual acuity, Multiple Sclerosis Impact Scale 29 items, version 2, Multiple Sclerosis Walking Scale, version 2, and questionnaires addressing pain and fatigue). The exploratory end points included measures of persistent new T1 hypointensities and grey matter volume changes. The substudies were advanced magnetic resonance imaging, optical coherence tomography and cerebrospinal fluid analyses., Results: Between December 2014 and June 2016, 445 patients were randomised (analysed) to amiloride [ n = 111 (99)], fluoxetine [ n = 111 (96)], riluzole [ n = 111 (99)] or placebo [ n = 112 (99)]. A total of 206 randomised patients consented to the advanced magnetic resonance imaging substudy, 260 consented to the optical coherence tomography substudy and 70 consented to the cerebrospinal fluid substudy. No significant difference was seen between the active drugs and placebo in percentage brain volume change at week 96 as follows (where negative values mean more atrophy than placebo): amiloride minus placebo 0.0% (Dunnett-adjusted 95% confidence interval –0.4% to 0.5%), fluoxetine minus placebo –0.1% (Dunnett-adjusted 95% confidence interval –0.5% to 0.3%); riluzole minus placebo –0.1% (Dunnett-adjusted 95% confidence interval –0.6% to 0.3%). There was good adherence to study drugs. The proportion of patients experiencing adverse events was similar in the treatment and placebo groups. There were no emergent safety issues., Limitations: There was a lower than expected uptake in the cerebrospinal fluid substudy., Conclusions: A multiarm Phase II paradigm is efficient in determining which neuroprotective agents to take through to Phase III trials. Amiloride, fluoxetine and riluzole were not effective in reducing the brain atrophy rate in people with secondary progressive multiple sclerosis. Mechanistic pathobiological insight was gained., Future Work: To use the information gained from the Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART) to inform future trial design as new candidate agents are identified., Trial Registration: Current Controlled Trials ISRCTN28440672, NCT01910259 and EudraCT 2012-005394-31., Funding: This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation ; Vol. 7, No. 3. See the NIHR Journals Library website for further project information. This trial also received funding from the UK MS Society and the US National Multiple Sclerosis Society., (Copyright © Queen’s Printer and Controller of HMSO 2020. This work was produced by De Angelis et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.)
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- 2020
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