Dataset Information

High-frequency motor rehabilitation in amyotrophic lateral sclerosis: a randomized clinical trial.

ABSTRACT: Objective:Exercise may be physically and psychologically important for people with ALS, especially in the earlier stages of the disease, and, as a consequence, current ALS clinical management includes individualized rehabilitation as part of multidisciplinary care because. However, while recent studies focused on which type of exercise is more indicated to ALS patients, there is no evidence at which frequency training sessions should be performed. Methods:We performed an assessor blinded randomized clinical trial to investigate the superiority of two different frequencies of exercise on rate of progression in ALS. We enrolled 65 patients in two groups: intensive exercise regimen (IER, five sessions/week) versus usual exercise regimen (UER, two sessions/week). The primary aim was to assess if IER decreased disease progression, measured through Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised, with respect to UER. Secondary aims included assessment of adverse events, tracheostomy-free survival, motor and respiratory functions, fatigue, quality of life and caregiver burden. Treatment regimen consisted for both groups of the same kind of exercise including aerobic training, endurance training, stretching or assisted active mobilization, differing for frequency of intervention. Results:No significant changes in disease progression were found in patients under IER versus UER. At the end of the study, there were no significant differences between the two groups in survival, respiratory function, time to supporting procedures, and quality of life. Adverse events, fatigue, and caregiver burden were not different between the two treatment regimens. Conclusions:Despite some limitations, our trial demonstrated that high-frequency physical exercise was not superior to UER on ALSFRS-R scores, motor and respiratory functions, survival, fatigue, and quality of life of ALS patients.

SUBMITTER: Zucchi E

PROVIDER: S-EPMC6529833 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

High-frequency motor rehabilitation in amyotrophic lateral sclerosis: a randomized clinical trial.

Zucchi Elisabetta E Vinceti Marco M Malagoli Carlotta C Fini Nicola N Gessani Annalisa A Fasano Antonio A Rizzi Romana R Sette Elisabetta E Cavazza Stefano S Fiocchi Alena A Buja Sergio S Faccioli Tiziana T Storani Simone S Mandrioli Jessica J

Annals of clinical and translational neurology 20190318 5

<h4>Objective</h4>Exercise may be physically and psychologically important for people with ALS, especially in the earlier stages of the disease, and, as a consequence, current ALS clinical management includes individualized rehabilitation as part of multidisciplinary care because. However, while recent studies focused on which type of exercise is more indicated to ALS patients, there is no evidence at which frequency training sessions should be performed.<h4>Methods</h4>We performed an assessor ...[more]

PMID: 31139687

Similar Datasets

Project description:ImportanceAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of the motor nervous system. Clinical studies have demonstrated cortical and spinal motor neuron hyperexcitability using transcranial magnetic stimulation and threshold tracking nerve conduction studies, respectively, although metrics of excitability have not been used as pharmacodynamic biomarkers in multi-site clinical trials.ObjectiveTo ascertain whether ezogabine decreases cortical and spinal motor neuron excitability in ALS.Design, setting, and participantsThis double-blind, placebo-controlled phase 2 randomized clinical trial sought consent from eligible participants from November 3, 2015, to November 9, 2017, and was conducted at 12 US sites within the Northeast ALS Consortium. Participants were randomized in equal numbers to a higher or lower dose of ezogabine or to an identical matched placebo, and they completed in-person visits at screening, baseline, week 6, and week 8 for clinical assessment and neurophysiological measurements.InterventionsParticipants were randomized to receive 600 mg/d or 900 mg/d of ezogabine or a matched placebo for 10 weeks.Main outcomes and measuresThe primary outcome was change in short-interval intracortical inhibition (SICI; SICI-1 was used in analysis to reflect stronger inhibition from an increase in amplitude) from pretreatment mean at screening and baseline to the full-dose treatment mean at weeks 6 and 8. The secondary outcomes included levels of cortical motor neuron excitability (including resting motor threshold) measured by transcranial magnetic stimulation and spinal motor neuron excitability (including strength-duration time constant) measured by threshold tracking nerve conduction studies.ResultsA total of 65 participants were randomized to placebo (23), 600 mg/d of ezogabine (23), and 900 mg/d of ezogabine (19 participants); 45 were men (69.2%) and the mean (SD) age was 58.3 (8.8) years. The SICI-1 increased by 53% (mean ratio, 1.53; 95% CI, 1.12-2.09; P = .009) in the 900-mg/d ezogabine group vs placebo group. The SICI-1 did not change in the 600-mg/d ezogabine group vs placebo group (mean ratio, 1.15; 95% CI, 0.87-1.52; P = .31). The resting motor threshold increased in the 600-mg/d ezogabine group vs placebo group (mean ratio, 4.61; 95% CI, 0.21-9.01; P = .04) but not in the 900-mg/d ezogabine group vs placebo group (mean ratio, 1.95; 95% CI, -2.64 to 6.54; P = .40). Ezogabine caused a dose-dependent decrease in excitability by several other metrics, including strength-duration time constant in the 900-mg/d ezogabine group vs placebo group (mean ratio, 0.73; 95% CI, 0.60 to 0.87; P < .001).Conclusions and relevanceEzogabine decreased cortical and spinal motor neuron excitability in participants with ALS, suggesting that such neurophysiological metrics may be used as pharmacodynamic biomarkers in multisite clinical trials.Trial registrationClinicalTrials.gov Identifier: NCT02450552.

Project description:Thoughtful clinical trial design is critical for efficient therapeutic development, particularly in the field of amyotrophic lateral sclerosis (ALS), where trials often aim to detect modest treatment effects among a population with heterogeneous disease progression. Appropriate outcome measure selection is necessary for trials to provide decisive and informative results. Investigators must consider the outcome measure's reliability, responsiveness to detect change when change has actually occurred, clinical relevance, and psychometric performance. ALS clinical trials can also be performed more efficiently by utilizing statistical enrichment techniques. Innovations in ALS prediction models allow for selection of participants with less heterogeneity in disease progression rates without requiring a lead-in period, or participants can be stratified according to predicted progression. Statistical enrichment can reduce the needed sample size and improve study power, but investigators must find a balance between optimizing statistical efficiency and retaining generalizability of study findings to the broader ALS population. Additional progress is still needed for biomarker development and validation to confirm target engagement in ALS treatment trials. Selection of an appropriate biofluid biomarker depends on the treatment mechanism of interest, and biomarker studies should be incorporated into early phase trials. Inclusion of patients with ALS as advisors and advocates can strengthen clinical trial design and study retention, but more engagement efforts are needed to improve diversity and equity in ALS research studies. Another challenge for ALS therapeutic development is identifying ways to respect patient autonomy and improve access to experimental treatment, something that is strongly desired by many patients with ALS and ALS advocacy organizations. Expanded access programs that run concurrently to well-designed and adequately powered randomized controlled trials may provide an opportunity to broaden access to promising therapeutics without compromising scientific integrity or rushing regulatory approval of therapies without adequate proof of efficacy.

Project description:Background and purposeAmyotrophic lateral sclerosis is a progressive motor neuron disorder that involves degeneration of both upper and lower motor neurons. In patients with amyotrophic lateral sclerosis, pathologic studies and ex vivo high-resolution MR imaging at ultra-high field strength revealed the co-localization of iron and activated microglia distributed in the deep layers of the primary motor cortex. The aims of the study were to measure the cortical thickness and evaluate the distribution of iron-related signal changes in the primary motor cortex of patients with amyotrophic lateral sclerosis as possible in vivo biomarkers of upper motor neuron impairment.Materials and methodsTwenty-two patients with definite amyotrophic lateral sclerosis and 14 healthy subjects underwent a high-resolution 2D multiecho gradient-recalled sequence targeted on the primary motor cortex by using a 7T scanner. Image analysis consisted of the visual evaluation and quantitative measurement of signal intensity and cortical thickness of the primary motor cortex in patients and controls. Qualitative and quantitative MR imaging parameters were correlated with electrophysiologic and laboratory data and with clinical scores.ResultsUltra-high field MR imaging revealed atrophy and signal hypointensity in the deep layers of the primary motor cortex of patients with amyotrophic lateral sclerosis with a diagnostic accuracy of 71%. Signal hypointensity of the deep layers of the primary motor cortex correlated with upper motor neuron impairment (r = -0.47; P < .001) and with disease progression rate (r = -0.60; P = .009).ConclusionsThe combined high spatial resolution and sensitivity to paramagnetic substances of 7T MR imaging demonstrate in vivo signal changes of the cerebral motor cortex that resemble the distribution of activated microglia within the cortex of patients with amyotrophic lateral sclerosis. Cortical thinning and signal hypointensity of the deep layers of the primary motor cortex could constitute a marker of upper motor neuron impairment in patients with amyotrophic lateral sclerosis.

Dataset Information

High-frequency motor rehabilitation in amyotrophic lateral sclerosis: a randomized clinical trial.

Publications

High-frequency motor rehabilitation in amyotrophic lateral sclerosis: a randomized clinical trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets