10 results on '"Kapoor, Raj"'
Search Results
2. Evaluation of multiple sclerosis disability outcome measures using pooled clinical trial data.
- Author
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Goldman MD, LaRocca NG, Rudick RA, Hudson LD, Chin PS, Francis GS, Jacobs A, Kapoor R, Matthews PM, Mowry EM, Balcer LJ, Panzara M, Phillips G, Uitdehaag BMJ, and Cohen JA
- Subjects
- Adolescent, Adult, Aged, Clinical Trials as Topic, Databases, Factual, Female, Humans, Male, Meta-Analysis as Topic, Middle Aged, Reproducibility of Results, Young Adult, Multiple Sclerosis physiopathology, Outcome Assessment, Health Care
- Abstract
Objective: We report analyses of a pooled database by the Multiple Sclerosis Outcome Assessments Consortium to evaluate 4 proposed components of a multidimensional test battery., Methods: Standardized data on 12,776 participants, comprising demographics, multiple sclerosis disease characteristics, Expanded Disability Status Scale (EDSS) score, performance measures, and Short Form-36 Physical Component Summary (SF-36 PCS), were pooled from control and treatment arms of 14 clinical trials. Analyses of Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), Low Contrast Letter Acuity (LCLA), and Symbol Digit Modalities Test (SDMT) included measurement properties; construct, convergent, and known group validity; and longitudinal performance of the measures individually and when combined into a multidimensional test battery relative to the EDSS and SF-36 to determine sensitivity and clinical meaningfulness., Results: The performance measures had excellent test-retest reliability and showed expected differences between subgroups based on disease duration and EDSS level. Progression rates in detecting time to 3-month confirmed worsening were lower for T25FW and 9HPT compared to EDSS, while progression rates for LCLA and SDMT were similar to EDSS. When the 4 measures were analyzed as a multidimensional measure rather than as individual measures, progression on any one performance measure was more sensitive than the EDSS. Worsening on the performance measures analyzed individually or as a multidimensional test battery was associated with clinically meaningful SF-36 PCS score worsening, supporting clinical meaningfulness of designated performance test score worsening., Conclusion: These results support the use of the 4 proposed performance measures, individually or combined into a multidimensional test battery as study outcome measures., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
- Published
- 2019
- Full Text
- View/download PDF
3. The MSOAC approach to developing performance outcomes to measure and monitor multiple sclerosis disability.
- Author
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LaRocca NG, Hudson LD, Rudick R, Amtmann D, Balcer L, Benedict R, Bermel R, Chang I, Chiaravalloti ND, Chin P, Cohen JA, Cutter GR, Davis MD, DeLuca J, Feys P, Francis G, Goldman MD, Hartley E, Kapoor R, Lublin F, Lundstrom G, Matthews PM, Mayo N, Meibach R, Miller DM, Motl RW, Mowry EM, Naismith R, Neville J, Panagoulias J, Panzara M, Phillips G, Robbins A, Sidovar MF, Smith KE, Sperling B, Uitdehaag BM, and Weaver J
- Subjects
- Humans, Databases, Factual, Disability Evaluation, Multiple Sclerosis, Outcome Assessment, Health Care standards
- Abstract
Background: The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was formed by the National MS Society to develop improved measures of multiple sclerosis (MS)-related disability., Objectives: (1) To assess the current literature and available data on functional performance outcome measures (PerfOs) and (2) to determine suitability of using PerfOs to quantify MS disability in MS clinical trials., Methods: (1) Identify disability dimensions common in MS; (2) conduct a comprehensive literature review of measures for those dimensions; (3) develop an MS Clinical Data Interchange Standards Consortium (CDISC) data standard; (4) create a database of standardized, pooled clinical trial data; (5) analyze the pooled data to assess psychometric properties of candidate measures; and (6) work with regulatory agencies to use the measures as primary or secondary outcomes in MS clinical trials., Conclusion: Considerable data exist supporting measures of the functional domains ambulation, manual dexterity, vision, and cognition. A CDISC standard for MS ( http://www.cdisc.org/therapeutic#MS ) was published, allowing pooling of clinical trial data. MSOAC member organizations contributed clinical data from 16 trials, including 14,370 subjects. Data from placebo-arm subjects are available to qualified researchers. This integrated, standardized dataset is being analyzed to support qualification of disability endpoints by regulatory agencies.
- Published
- 2018
- Full Text
- View/download PDF
4. Advanced MRI measures like DTI or fMRI should be outcome measures in future clinical trials - YES.
- Author
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Kapoor R
- Subjects
- Humans, Multiple Sclerosis drug therapy, Multiple Sclerosis pathology, Multiple Sclerosis physiopathology, Clinical Trials as Topic, Diffusion Tensor Imaging, Functional Neuroimaging, Magnetic Resonance Imaging, Multiple Sclerosis diagnostic imaging, Outcome Assessment, Health Care
- Published
- 2017
- Full Text
- View/download PDF
5. Biomarker report from the phase II lamotrigine trial in secondary progressive MS - neurofilament as a surrogate of disease progression.
- Author
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Gnanapavan S, Grant D, Morant S, Furby J, Hayton T, Teunissen CE, Leoni V, Marta M, Brenner R, Palace J, Miller DH, Kapoor R, and Giovannoni G
- Subjects
- Atrophy complications, Biomarkers blood, Biomarkers cerebrospinal fluid, Brain drug effects, Brain metabolism, Brain pathology, Female, Humans, Lamotrigine, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis complications, Multiple Sclerosis diagnosis, Prognosis, Spinal Cord drug effects, Spinal Cord metabolism, Spinal Cord pathology, Time Factors, Treatment Outcome, Clinical Trials, Phase II as Topic, Disease Progression, Multiple Sclerosis drug therapy, Multiple Sclerosis metabolism, Neurofilament Proteins blood, Neurofilament Proteins cerebrospinal fluid, Triazines therapeutic use
- Abstract
Objective: Lamotrigine trial in SPMS was a randomised control trial to assess whether partial blockade of sodium channels has a neuroprotective effect. The current study was an additional study to investigate the value of neurofilament (NfH) and other biomarkers in predicting prognosis and/or response to treatment., Methods: SPMS patients who attended the NHNN or the Royal Free Hospital, UK, eligible for inclusion were invited to participate in the biomarker study. Primary outcome was whether lamotrigine would significantly reduce detectable serum NfH at 0-12, 12-24 and 0-24 months compared to placebo. Other serum/plasma and CSF biomarkers were also explored., Results: Treatment effect by comparing absolute changes in NfH between the lamotrigine and placebo group showed no difference, however based on serum lamotrigine adherence there was significant decline in NfH (NfH 12-24 months p=0.043, Nfh 0-24 months p=0.023). Serum NfH correlated with disability: walking times, 9-HPT (non-dominant hand), PASAT, z-score, MSIS-29 (psychological) and EDSS and MRI cerebral atrophy and MTR. Other biomarkers explored in this study were not found to be significantly associated, aside from that of plasma osteopontin., Conclusions: The relations between NfH and clinical scores of disability and MRI measures of atrophy and disease burden support NfH being a potential surrogate endpoint complementing MRI in neuroprotective trials and sample sizes for such trials are presented here. We did not observe a reduction in NfH levels between the Lamotrigine and placebo arms, however, the reduction in serum NfH levels based on lamotrigine adherence points to a possible neuroprotective effect of lamotrigine on axonal degeneration.
- Published
- 2013
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6. Systematic approach to selecting licensed drugs for repurposing in the treatment of progressive multiple sclerosis.
- Author
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Cunniffe, Nick, Vuong, Khue Anh, Ainslie, Debbie, Baker, David, Beveridge, Judy, Bickley, Sorrel, Camilleri, Patrick, Craner, Matthew, Fitzgerald, Denise, de la Fuente, Alerie G., Giovannoni, Gavin, Gray, Emma, Hazlehurst, Lorraine, Kapoor, Raj, Kaur, Ranjit, Kozlowski, David, Lumicisi, Brooke, Mahad, Don, Neumann, Björn, and Palmer, Alan
- Subjects
MULTIPLE sclerosis ,BLOOD-brain barrier ,DRUGS ,CLINICAL drug trials ,NIACIN ,RESEARCH ,ANIMAL experimentation ,RESEARCH methodology ,MEDICAL cooperation ,EVALUATION research ,COMPARATIVE studies ,RESEARCH funding ,MEDICAL prescriptions - Abstract
Objective: To establish a rigorous, expert-led, evidence-based approach to the evaluation of licensed drugs for repurposing and testing in clinical trials of people with progressive multiple sclerosis (MS).Methods: We long-listed licensed drugs with evidence of human safety, blood-brain barrier penetrance and demonstrable efficacy in at least one animal model, or mechanistic target, agreed by a panel of experts and people with MS to be relevant to the pathogenesis of progression. We systematically reviewed the preclinical and clinical literature for each compound, condensed this into a database of summary documents and short-listed drugs by scoring each one of them. Drugs were evaluated for immediate use in a clinical trial, and our selection was scrutinised by a final independent expert review.Results: From a short list of 55 treatments, we recommended four treatments for immediate testing in progressive MS: R-α-lipoic acid, metformin, the combination treatment of R-α-lipoic acid and metformin, and niacin. We also prioritised clemastine, lamotrigine, oxcarbazepine, nimodipine and flunarizine.Conclusions: We report a standardised approach for the identification of candidate drugs for repurposing in the treatment of progressive MS. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
7. The MSOAC approach to developing performance outcomes to measure and monitor multiple sclerosis disability.
- Author
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LaRocca, Nicholas G., Hudson, Lynn D., Rudick, Richard, Amtmann, Dagmar, Balcer, Laura, Benedict, Ralph, Bermel, Robert, Chang, Ih, Chiaravalloti, Nancy D., Chin, Peter, Cohen, Jeffrey A., Cutter, Gary R., Davis, Mat D., DeLuca, John, Feys, Peter, Francis, Gordon, Goldman, Myla D., Hartley, Emily, Kapoor, Raj, and Lublin, Fred
- Subjects
MULTIPLE sclerosis ,HEALTH outcome assessment ,CLINICAL trials ,MULTIPLE sclerosis research ,MULTIPLE sclerosis treatment - Abstract
Background: The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was formed by the National MS Society to develop improved measures of multiple sclerosis (MS)-related disability. Objectives: (1) To assess the current literature and available data on functional performance outcome measures (PerfOs) and (2) to determine suitability of using PerfOs to quantify MS disability in MS clinical trials. Methods: (1) Identify disability dimensions common in MS; (2) conduct a comprehensive literature review of measures for those dimensions; (3) develop an MS Clinical Data Interchange Standards Consortium (CDISC) data standard; (4) create a database of standardized, pooled clinical trial data; (5) analyze the pooled data to assess psychometric properties of candidate measures; and (6) work with regulatory agencies to use the measures as primary or secondary outcomes in MS clinical trials. Conclusion: Considerable data exist supporting measures of the functional domains ambulation, manual dexterity, vision, and cognition. A CDISC standard for MS (
http://www.cdisc.org/therapeutic#MS ) was published, allowing pooling of clinical trial data. MSOAC member organizations contributed clinical data from 16 trials, including 14,370 subjects. Data from placebo-arm subjects are available to qualified researchers. This integrated, standardized dataset is being analyzed to support qualification of disability endpoints by regulatory agencies. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
8. The EDSS-Plus, an improved endpoint for disability progression in secondary progressive multiple sclerosis.
- Author
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Cadavid, Diego, Kinch, Deborah, Lee, Sophia, Shang, Shulian, Mikol, Daniel, Sellebjerg, Finn, Cohen, Jeffrey A., Freedman, Mark S., Goldman, Myla D., Hartung, Hans-Peter, Havrdova, Eva, Jeffery, Douglas, Kapoor, Raj, and Miller, Aaron
- Subjects
MULTIPLE sclerosis diagnosis ,DISABILITY identification ,DISEASE progression ,MEASUREMENT of the anatomical extremities ,COGNITIVE analysis ,MULTIPLE sclerosis ,PATIENTS - Abstract
Background: The Expanded Disability Status Scale (EDSS) has wide scientific and regulatory precedent but limited ability to detect clinically relevant disability progression in secondary progressive multiple sclerosis (SPMS) patients, partly due to a lack of meaningful measurement of short-distance ambulatory and upper-extremity function. Objective: To present a rationale for a composite endpoint adding the timed 25-foot walk (T25FW) and 9-Hole Peg Test (9HPT) to EDSS for SPMS disability progression assessment. Methods: Using the International Multiple Sclerosis Secondary Progressive Avonex Clinical Trial (IMPACT) placebo arm (n = 215) data, we analyzed disability progression using a novel progression endpoint, “EDSS-Plus,” defined as progression on ⩾1 of 3 components (EDSS, T25FW, and/or 9HPT) confirmed ⩾24 weeks apart and with a ⩾20% minimum threshold change for T25FW and 9HPT. Results: Over 2 years, subjects classified as T25FW, 9HPT (dominant hand), or 9HPT (non-dominant hand) progressors worsened on average by 103.4%, 69.0%, and 59.2%, respectively, while non-progressors’ times remained largely unchanged. Using EDSS-Plus, 59.5% of the patients had 24-week confirmed disability progression versus 24.7% (EDSS), 41.9% (T25FW), and 34.4% (9HPT (either hand)) on each component alone. Conclusion: The 24-week confirmed minimum worsening of ⩾20% for T25FW and 9HPT clearly separates SPMS progressors from non-progressors. We propose that EDSS-Plus may represent an improved endpoint to identify SPMS disability progression. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
9. Setting a research agenda for progressive multiple sclerosis: The International Collaborative on Progressive MS.
- Author
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Fox, Robert J, Thompson, Alan, Baker, David, Baneke, Peer, Brown, Doug, Browne, Paul, Chandraratna, Dhia, Ciccarelli, Olga, Coetzee, Timothy, Comi, Giancarlo, Feinstein, Anthony, Kapoor, Raj, Lee, Karen, Salvetti, Marco, Sharrock, Kersten, Toosy, Ahmed, Zaratin, Paola, and Zuidwijk, Kim
- Subjects
MULTIPLE sclerosis treatment ,DISEASE progression ,SYMPTOMS ,CLINICAL indications ,DISEASE management ,CLINICAL medicine - Abstract
Despite significant progress in the development of therapies for relapsing MS, progressive MS remains comparatively disappointing. Our objective, in this paper, is to review the current challenges in developing therapies for progressive MS and identify key priority areas for research. A collaborative was convened by volunteer and staff leaders from several MS societies with the mission to expedite the development of effective disease-modifying and symptom management therapies for progressive forms of multiple sclerosis. Through a series of scientific and strategic planning meetings, the collaborative identified and developed new perspectives on five key priority areas for research: experimental models, identification and validation of targets and repurposing opportunities, proof-of-concept clinical trial strategies, clinical outcome measures, and symptom management and rehabilitation. Our conclusions, tackling the impediments in developing therapies for progressive MS will require an integrated, multi-disciplinary approach to enable effective translation of research into therapies for progressive MS. Engagement of the MS research community through an international effort is needed to address and fund these research priorities with the ultimate goal of expediting the development of disease-modifying and symptom-relief treatments for progressive MS. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
10. Systematic approach to selecting licensed drugs for repurposing in the treatment of progressive multiple sclerosis
- Author
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Cunniffe, Nick, Vuong, Khue Anh, Ainslie, Debbie, Baker, David, Beveridge, Judy, Bickley, Sorrel, Camilleri, Patrick, Craner, Matthew, Fitzgerald, Denise, De La Fuente, Alerie G, Giovannoni, Gavin, Gray, Emma, Hazlehurst, Lorraine, Kapoor, Raj, Kaur, Ranjit, Kozlowski, David, Lumicisi, Brooke, Mahad, Don, Neumann, Björn, Palmer, Alan, Peruzzotti-Jametti, Luca, Pluchino, Stefano, Robertson, Jennifer, Rothaul, Alan, Shellard, Lyndsey, Smith, Kenneth J, Wilkins, Alastair, Williams, Anna, and Coles, Alasdair
- Subjects
Multiple sclerosis ,3. Good health - Abstract
Objective: To establish a rigorous, expert-led, evidence-based approach to the evaluation of licensed drugs for repurposing and testing in clinical trials of people with progressive multiple sclerosis (MS). Methods: We long-listed licensed drugs with evidence of human safety, blood–brain barrier penetrance and demonstrable efficacy in at least one animal model, or mechanistic target, agreed by a panel of experts and people with MS to be relevant to the pathogenesis of progression. We systematically reviewed the preclinical and clinical literature for each compound, condensed this into a database of summary documents and short-listed drugs by scoring each one of them. Drugs were evaluated for immediate use in a clinical trial, and our selection was scrutinised by a final independent expert review. Results: From a short list of 55 treatments, we recommended four treatments for immediate testing in progressive MS: R-α-lipoic acid, metformin, the combination treatment of R-α-lipoic acid and metformin, and niacin. We also prioritised clemastine, lamotrigine, oxcarbazepine, nimodipine and flunarizine. Conclusions: We report a standardised approach for the identification of candidate drugs for repurposing in the treatment of progressive MS.
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