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Artigo em Inglês | MEDLINE | ID: mdl-34949141


Objective: Uniform data collection is fundamental for multicentre clinical trials. We aim to determine the variability, between ALS trial centers, in the prevalence of unexpected or implausible improvements in the revised ALS functional rating scale (ALSFRS-R) score, and its associations with individual patient and item characteristics.Methods: We used data from two multicentre studies to estimate the prevalence of an unexpected increase or implausible improvement in the ALSFRS-R score, defined as an increase of 5 points or more between two consecutive, monthly visits. For each patient with a 5-point or more increase, we evaluated the individual contribution of each ALSFRS-R item.Results: Longitudinal ALSFRS-R scores, originating from 114 trial centers enrolling a total of 1,240 patients, were analyzed. A 5-point or more increase in ALSFRS-R total score was found in 151 (12.2%) patients, with prevalence per study center ranging from 0% to 83%. Bulbar onset, faster disease progression at enrollment, and a lower ALSFRS-R score at baseline were associated with a sudden 5-point or more increase in the ALSFRS-R total score. ALSFRS-R items 2 (saliva), 9 (stairs), 10 (dyspnea), and 11 (orthopnea) were the primary drivers when a 5-point or more increase occurred.Conclusions: Sudden 5-point or more increases in ALSFRS-R total scores between two consecutive visits are relatively common. These sudden increases were not found to occur with equal frequency in trial centers; which underscores the need for amending existing standard operating procedures toward a universal version and monitoring of data quality during the study, in multicentre research.

Artigo em Inglês | MEDLINE | ID: mdl-32627599


OBJECTIVE: A recent case-series described patients with ALS to improve and/or stabilize after treatment with intravenous high-dose Penicillin G/Hydrocortisone (PenGH). In this study, we determine the safety and efficacy of intravenous PenGH versus placebo in combination with riluzole in patients with ALS. METHODS: Patients diagnosed with ALS according to the El Escorial criteria were randomized double-blind to four quarterly cycles of 21 d of intravenous PenGH or placebo in a 5:3 ratio. The primary outcome was change from baseline to week 48 in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R). Secondary outcomes were lung function, muscle strength, plasma creatinine, clinical stage, gastrostomy placement, quality of life and occurrence of adverse of events. RESULTS: In total, 16 patients were randomized (10 PenGH and 6 placebo), of which 6 (40%) completed the study. Patients treated with PenGH progressed with 2.2 (95% CI 1.1-3.3) ALSFRS-R points per month and PenGH treatment did not halt disease progression (p = 0.002). No significant differences were found between PenGH or placebo (mean difference 0.5, 95% CI -1.01 to ∞, p = 0.28). Although PenGH was well-tolerated, 6 patients (38%, 3 in each arm) had thrombotic complications due to the intravenous administration method. CONCLUSIONS: Treatment with PenGH does not halt disease or reverse progression in patients with ALS and showed no statistical difference with those who received placebo. Prolonged intravenous administration therapies may inflate thrombosis risk.

Esclerose Amiotrófica Lateral , Esclerose Amiotrófica Lateral/tratamento farmacológico , Método Duplo-Cego , Humanos , Hidrocortisona , Penicilina G , Qualidade de Vida
J Neurol ; 266(10): 2387-2395, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31187191


BACKGROUND: The extensive heterogeneity between patients with amyotrophic lateral sclerosis (ALS) complicates the quantification of disease progression. In this study, we determine the value of remote, accelerometer-based monitoring of physical activity in patients with ALS. METHODS: This longitudinal cohort study was conducted in a home-based setting; all study materials were sent by mail. Patients wore the ActiGraph during waking hours for 7 days every 2-3 months and provided information regarding their daily functioning (ALSFRS-R). We defined four accelerometer-based endpoints that either reflect the average daily activity or quantify the patient's physical capacity. RESULTS: A total of 42 patients participated; the total valid monitoring period was 9288 h with a 93.0% adherence rate. At baseline, patients were active 27.9% (range 11.6-52.4%) of their time; this declined by 0.64% (95% 0.43-0.86, p < 0.001) per month. Accelerometer-based endpoints were strongly associated with the ALSFRS-R (r 0.78, 95% CI 0.63-0.92, p < 0.001), but showed less variability over time than the ALSFRS-R (coefficient of variation 0.64-0.81 vs. 1.06, respectively). Accelerometer-based endpoints could reduce sample size by 30.3% for 12-month trials and 44.6% for 18-month trials; for trials lasting less than 9 months, the ALSFRS-R resulted in smaller sample sizes. CONCLUSION: Accelerometry is an objective method for quantifying disease progression, which could obtain real-world insights in the patient's physical functioning and may personalize the delivery of care. In addition, remote monitoring provides patients with the opportunity to participate in clinical trials from home, paving the way to a patient-centric clinical trial model.

Acelerometria/normas , Esclerose Amiotrófica Lateral/diagnóstico , Esclerose Amiotrófica Lateral/fisiopatologia , Progressão da Doença , Exercício Físico , Monitorização Ambulatorial/normas , Idoso , Exercício Físico/fisiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes