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42 results on '"Van Eijk, Ruben P.A."'

8. The ALSFRS-R Summit: a global call to action on the use of the ALSFRS-R in ALS clinical trials.

Author

Genge, Angela, Cedarbaum, Jesse M., Shefner, Jeremy, Chio, Adriano, Al-Chalabi, Ammar, Van Damme, Philip, McDermott, Chris, Glass, Jonathan, Berry, James, van Eijk, Ruben P.A., Fournier, Christina, Grosskreutz, Julian, Andrews, Jinsy, Bertone, Vanessa, Bunte, Tommy M, Couillard, Mathias, Cummings, Cathy, Kittle, Gale, Polzer, John, and Salmon, Kristiana

Subjects
CLINICAL trials, AMYOTROPHIC lateral sclerosis, EXPERIMENTAL design
Abstract

The Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) was developed more than 25 years ago as an instrument to monitor functional change over time in patients with ALS. It has since been revised and extended to meet the needs of high data quality in ALS trials (ALSFRS-R), however a full re-validation of the scale was not completed. Despite this, the scale has remained a primary outcome measure in clinical trials. We convened a group of clinical trialists to discuss and explore opportunities to improve the scale and propose alternative measures. In this meeting report, we present a call to action on the use of the ALSFRS-Revised scale in clinical trials, focusing on the need for (1) harmonization of the ALSFRS-R administration globally, (2) alignment on a set of recommendations for clinical trial design and statistical analysis plans (SAPs), and (3) use of additional outcome measures. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Assessment of risk of ALS conferred by the GGGGCC hexanucleotide repeat expansion in C9orf72 among first-degree relatives of patients with ALS carrying the repeat expansion.

Author

Van Wijk, Iris F., Van Eijk, Ruben P.A., Van Boxmeer, Loes, Westeneng, Henk-Jan, Van Es, Michael A., Van Rheenen, Wouter, Van Den Berg, Leonard H., Eijkemans, Marinus J.C., and Veldink, Jan H.

Subjects
*RISK assessment, *RANDOM effects model, *RELATIVES
Abstract

We aimed to estimate the age-related risk of ALS in first-degree relatives of patients with ALS carrying the C9orf72 repeat expansion. We included all patients with ALS carrying a C9orf72 repeat expansion in The Netherlands. Using structured questionnaires, we determined the number of first-degree relatives, their age at death due to ALS or another cause, or age at time of questionnaire. The cumulative incidence of ALS among first-degree relatives was estimated, while accounting for death from other causes. Variability in ALS risk between families was evaluated using a random effects hazards model. We used a second, distinct approach to estimate the risk of ALS and FTD in the general population, using previously published data. In total, 214 of the 2,486 (9.2%) patients with ALS carried the C9orf72 repeat expansion. The mean risk of ALS at age 80 for first-degree relatives carrying the repeat expansion was 24.1%, but ranged between individual families from 16.0 to 60.6%. Using the second approach, we found the risk of ALS and FTD combined was 28.7% (95% CI 17.8%–54.3%) for carriers in the general population. On average, our estimated risk of ALS in the C9orf72 repeat expansion was lower compared to historical estimates. We showed, however, that the risk of ALS likely varies between families and one overall penetrance estimate may not be sufficient to describe ALS risk. This warrants a tailor-made, patient-specific approach in testing. Further studies are needed to assess the risk of FTD in the C9orf72 repeat expansion. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Development of a Rasch-Built Amyotrophic Lateral Sclerosis Impairment Multidomain Scale to Measure Disease Progression in ALS

Author

de Jongh, Adriaan D., primary, van Eijk, Ruben P.A., additional, Bakker, Leonhard A., additional, Bunte, Tommy M., additional, Beelen, Anita, additional, van der Meijden, Conny, additional, van Es, Michael A., additional, Visser-Meily, Johanna M.A., additional, Kruitwagen, Esther T., additional, Veldink, Jan H., additional, and van den Berg, Leonard H., additional

Published
2023
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15. Development and Evaluation of a Simulation-Based Algorithm to Optimize the Planning of Interim Analyses for Clinical Trials in ALS

Author

van Unnik, Jordi W.J., primary, Nikolakopoulos, Stavros, additional, Eijkemans, Marinus J.C, additional, Gonzalez-Bermejo, Jésus, additional, Bruneteau, Gaelle, additional, Morelot-Panzini, Capucine, additional, van den Berg, Leonard H., additional, Cudkowicz, Merit E., additional, McDermott, Christopher J., additional, Similowski, Thomas, additional, and van Eijk, Ruben P.A., additional

Published
2023
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20. Portable fixed dynamometry enables home-based, reliable assessment of muscle strength in patients with amyotrophic lateral sclerosis: a pilot study.

Author

Van Unnik, Jordi W. J., Bakers, Jaap N.E., Kokx, Steure, Van Den Berg, Leonard H., Visser-Meily, Johanna M.A., Beelen, Anita, and Van Eijk, Ruben P.A.

Subjects
AMYOTROPHIC lateral sclerosis, MUSCLE strength, MEASUREMENT errors, STATISTICAL reliability, PILOT projects
Abstract

To determine the feasibility, reliability, and sensitivity of remotely monitoring muscle strength loss of knee extensors using a novel portable fixed dynamometer (PFD) in patients with amyotrophic lateral sclerosis (ALS). We conducted a pilot study with a newly developed device to measure knee extension strength. Patients performed unsupervised PFD measurements, biweekly, for 6 months at home. We evaluated feasibility using adherence and a device-specific questionnaire. Reliability was assessed by (1) comparing unsupervised and supervised measurements to identify systematic bias, and (2) comparing consecutive unsupervised measurements to determine test-retest reliability expressed as intraclass correlation coefficient (ICC) and standard error of measurement (SEM). Sensitivity to detect longitudinal change was described using linear mixed-effects models. We enrolled 18 patients with ALS. Adherence was 86%, where all patients found that the device suitable to measure muscle strength at home; 4 patients (24%) found the measurements burdensome. The correlation between (un)supervised measurements was excellent (Pearson's r 0.97, 95%CI; 0.94 − 0.99) and no systematic bias was present (mean difference 0.13, 95%CI; −2.22 − 2.48, p = 0.91). Unsupervised measurements had excellent test-retest reliability with an average ICC of 0.97 (95%CI: 0.94 − 0.99) and SEM of 5.8% (95%CI: 4.8 − 7.0). Muscle strength declined monthly by 1.9 %predicted points (95%CI; −3.0 to −0.9, p = 0.001). Using the PFD, it proved feasible to perform knee extension strength measurements at home which were reliable and sensitive for detecting muscle strength loss. Larger studies are warranted to compare the device with conventional outcomes. [ABSTRACT FROM AUTHOR]

Published
2023
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26. Meta-analysis of pharmacogenetic interactions in amyotrophic lateral sclerosis clinical trials

Author

van Eijk, Ruben P.A., Jones, Ashley R., Sproviero, William, Shatunov, Aleksey, Shaw, Pamela J., Leigh, P. Nigel, Young, Carolyn A., Shaw, Christopher E., Mora, Gabriele, Mandrioli, Jessica, Borghero, Giuseppe, Volanti, Paolo, Diekstra, Frank P., van Rheenen, Wouter, Verstraete, Esther, Eijkemans, Marinus J.C., Veldink, Jan H., Chio, Adriano, Al-Chalabi, Ammar, van den Berg, Leonard H., and van Es, Michael A.

Published
2017
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27. Innovating Clinical Trials for Amyotrophic Lateral Sclerosis

Author

van Eijk, Ruben P.A., Nikolakopoulos, Stavros, Roes, Kit C.B., Kendall, Lindsay, Han, Steve S., Lavrov, Arseniy, Epstein, Noam, Kliest, Tessa, de Jongh, Adriaan D., Westeneng, Henk-Jan, Al-Chalabi, Ammar, Van Damme, Philip, Hardiman, Orla, Shaw, Pamela J., McDermott, Christopher J., Eijkemans, Marinus J.C., and van den Berg, Leonard H.

Subjects
Clinical Trials as Topic, Research Design, Risk Factors, Patient Selection, Amyotrophic Lateral Sclerosis, Disease Progression, Humans, Contemporary Issues in Practice, Education, & Research
Abstract

Development of effective treatments for amyotrophic lateral sclerosis (ALS) has been hampered by disease heterogeneity, a limited understanding of underlying pathophysiology, and methodologic design challenges. We have evaluated 2 major themes in the design of pivotal, phase 3 clinical trials for ALS-(1) patient selection and (2) analytical strategy-and discussed potential solutions with the European Medicines Agency. Several design considerations were assessed using data from 5 placebo-controlled clinical trials (n = 988), 4 population-based cohorts (n = 5,100), and 2,436 placebo-allocated patients from the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database. The validity of each proposed design modification was confirmed by means of simulation and illustrated for a hypothetical setting. Compared to classical trial design, the proposed design modifications reduce the sample size by 30.5% and placebo exposure time by 35.4%. By making use of prognostic survival models, one creates a potential to include a larger proportion of the population and maximize generalizability. We propose a flexible design framework that naturally adapts the trial duration when inaccurate assumptions are made at the design stage, such as enrollment or survival rate. In case of futility, the follow-up time is shortened and patient exposure to ineffective treatments or placebo is minimized. For diseases such as ALS, optimizing the use of resources, widening eligibility criteria, and minimizing exposure to futile treatments and placebo is critical to the development of effective treatments. Our proposed design modifications could circumvent important pitfalls and may serve as a blueprint for future clinical trials in this population.

Published
2021

28. Clinical relevance of testing for metabolic vitamin B12 deficiency in patients with polyneuropathy.

Author

Warendorf, Janna K., van Doormaal, Perry T.C., Vrancken, Alexander F.J.E., Verhoeven-Duif, Nanda M., van Eijk, Ruben P.A., van den Berg, Leonard H., and Notermans, Nicolette C.

Subjects
VITAMIN B12 deficiency, DIABETIC neuropathies, POLYNEUROPATHIES, DIETARY supplements, METHYLMALONIC acid, POLYHYDRAMNIOS, VITAMIN B12
Abstract

Determine vitamin B12 threshold levels below which additional testing of methylmalonic acid (MMA) and/or homocysteine (Hcy) is useful to diagnose metabolic vitamin B12 deficiency in patients with polyneuropathy, and how vitamin B12, MMA and Hcy levels relate to the effect of supplementation therapy. In a retrospective cohort study of 331 patients with polyneuropathy, vitamin B12, MMA and Hcy were measured. Linear regression models with vitamin B12 as dependent and Hcy or MMA as covariate were compared, to assess which was best related to vitamin B12. Threshold vitamin B12 levels for metabolic deficiency (defined as elevatede metabolites) were determined using logistic regression with elevated metabolites as dependent and vitamin B12 as covariate. A structured interview was conducted in 42 patients to evaluate response to vitamin B12 supplementation. MMA was best related to vitamin B12. Using elevated MMA for metabolic deficiency, we found 90% sensitivity at a vitamin B12 threshold level <264 pmol/L (358 pg/mL) and 95% sensitivity at <304 pmol/L (412 pg/mL). Improvement after supplementation was reported by 19% patients and stabilization by 24%. 88% of patients with improvement and 90% with stabilization either had absolute deficiency (Vitamin B12 < 148 pmol/L) or metabolic deficiency (elevated MMA and vitamin B12 ≥ 148 pmol/L). There were no additional patients with improvement or stabilization with isolated elevated Hcy. Testing of MMA has additional value in identifying patients with clinically relevant metabolic deficiency when vitamin B12 is below 304 pmol/L (412 pg/mL). Supplementation can be effective in patients with absolute and metabolic deficiency. [ABSTRACT FROM AUTHOR]

Published
2022
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30. Clinical trials in pediatric ALS: a TRICALS feasibility study

Author

Kliest, Tessa, primary, Van Eijk, Ruben P.A., additional, Al-Chalabi, Ammar, additional, Albanese, Alberto, additional, Andersen, Peter M., additional, Amador, Maria Del Mar, additional, BrÅthen, Geir, additional, Brunaud-Danel, Veronique, additional, Brylev, Lev, additional, Camu, William, additional, De Carvalho, Mamede, additional, Cereda, Cristina, additional, Cetin, Hakan, additional, Chaverri, Delia, additional, Chiò, Adriano, additional, Corcia, Philippe, additional, Couratier, Philippe, additional, De Marchi, Fabiola, additional, Desnuelle, Claude, additional, Van Es, Michael A., additional, Esteban, JesÚs, additional, Filosto, Massimiliano, additional, GarcÍa Redondo, Alberto, additional, Grosskreutz, Julian, additional, Hanemann, Clemens O., additional, HolmØy, Trygve, additional, HØyer, Helle, additional, Ingre, Caroline, additional, Koritnik, Blaz, additional, Kuzma-Kozakiewicz, Magdalena, additional, Lambert, Thomas, additional, Leigh, Peter N., additional, Lunetta, Christian, additional, Mandrioli, Jessica, additional, Mcdermott, Christopher J., additional, Meyer, Thomas, additional, Mora, Jesus S., additional, Petri, Susanne, additional, Povedano, MÓnica, additional, Reviers, Evy, additional, Riva, Nilo, additional, Roes, Kit C.B., additional, Rubio, Miguel Á., additional, Salachas, FranÇois, additional, Sarafov, Stayko, additional, SorarÙ, Gianni, additional, Stevic, Zorica, additional, Svenstrup, Kirsten, additional, MØller, Anette Torvin, additional, Turner, Martin R., additional, Van Damme, Philip, additional, Van Leeuwen, Lucie A.G., additional, Varona, Luis, additional, VÁzquez Costa, Juan F., additional, Weber, Markus, additional, Hardiman, Orla, additional, and Van Den Berg, Leonard H., additional

Published
2022
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33. A roadmap for remote digital health technology for Motor Neuron Disease (Preprint)

Author

van Eijk, Ruben P.A., primary, Beelen, Anita, additional, Kruitwagen, Esther T., additional, Murray, Deirdre, additional, Radakovic, Ratko, additional, Hobson, Esther, additional, Knox, Liam, additional, Helleman, Jochem, additional, Burke, Tom, additional, Rubio Pérez, Miguel Ángel, additional, Reviers, Evy, additional, Ferguson, Toby A., additional, Genge, Angela, additional, Steyn, Frederik J., additional, Ngo, Shyuan, additional, Eaglesham, John, additional, Roes, Kit C.B., additional, van den Berg, Leonard H., additional, Hardiman, Orla, additional, and McDermott, Christopher J., additional

Published
2021
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36. TRICALS: creating a highway toward a cure

Author

van Eijk, Ruben P.A., primary, Kliest, Tessa, additional, McDermott, Christopher J., additional, Roes, Kit C.B., additional, Van Damme, Philip, additional, Chio, Adriano, additional, Weber, Markus, additional, Ingre, Caroline, additional, Corcia, Philippe, additional, Povedano, Mònica, additional, Reviers, Evy, additional, van Es, Michael A., additional, Al-Chalabi, Ammar, additional, Hardiman, Orla, additional, and van den Berg, Leonard H., additional

Published
2020
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38. Relative hyperventilation in non-ventilated patients with spinal muscular atrophy

Author

Veldhoen, Esther S., primary, Wijngaarde, Camiel A., additional, Verweij-van den Oudenrijn, Laura P., additional, Asselman, Fay-Lynn, additional, Wösten-van Asperen, Roelie M., additional, Hulzebos, Erik H.J., additional, van der Ent, Kors, additional, Cuppen, Inge, additional, Gaytant, Michael A., additional, van Eijk, Ruben P.A., additional, and van der Pol, W. Ludo, additional

Published
2020
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