Dataset Information

Pilot trial of inosine to elevate urate levels in amyotrophic lateral sclerosis.

ABSTRACT: Objective:To test the safety, tolerability, and urate-elevating capability of the urate precursor inosine taken orally or by feeding tube in people with amyotrophic lateral sclerosis (ALS). Methods:This was a pilot, open-label trial in 25 participants with ALS. Treatment duration was 12 weeks. The dose of inosine was titrated at pre-specified time points to elevate serum urate levels to 7-8 mg/dL. Primary outcomes were safety (as assessed by the occurrence of adverse events [AEs]) and tolerability (defined as the ability to complete the 12-week study on study drug). Secondary outcomes included biomarkers of oxidative stress and damage. As an exploratory analysis, observed outcomes were compared with a virtual control arm built using prediction algorithms to estimate ALSFRS-R scores. Results:Twenty-four out of 25 participants (96%) completed 12 weeks of study drug treatment. One participant was unable to comply with study visits and was lost to follow-up. Serum urate rose to target levels in 6 weeks. No serious AEs attributed to study drug and no AEs of special concern, such as urolithiasis and gout, occurred. Selected biomarkers of oxidative stress and damage had significant changes during the study period. Observed changes in ALSFRS-R did not differ from baseline predictions. Interpretation:Inosine appeared safe, well tolerated, and effective in raising serum urate levels in people with ALS. These findings, together with epidemiological observations and preclinical data supporting a neuroprotective role of urate in ALS models, provide the rationale for larger clinical trials testing inosine as a potential disease-modifying therapy for ALS.

SUBMITTER: Nicholson K

PROVIDER: S-EPMC6292193 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pilot trial of inosine to elevate urate levels in amyotrophic lateral sclerosis.

Nicholson Katharine K Chan James J Macklin Eric A EA Levine-Weinberg Mark M Breen Christopher C Bakshi Rachit R Grasso Daniela L DL Wills Anne-Marie AM Jahandideh Samad S Taylor Albert A AA Beaulieu Danielle D Ennist David L DL Andronesi Ovidiu O Ratai Eva-Maria EM Schwarzschild Michael A MA Cudkowicz Merit M Paganoni Sabrina S

Annals of clinical and translational neurology 20181022 12

<h4>Objective</h4>To test the safety, tolerability, and urate-elevating capability of the urate precursor inosine taken orally or by feeding tube in people with amyotrophic lateral sclerosis (ALS).<h4>Methods</h4>This was a pilot, open-label trial in 25 participants with ALS. Treatment duration was 12 weeks. The dose of inosine was titrated at pre-specified time points to elevate serum urate levels to 7-8 mg/dL. Primary outcomes were safety (as assessed by the occurrence of adverse events [AEs]) ...[more]

PMID: 30564619

Similar Datasets

Project description:BackgroundPatients with amyotrophic lateral sclerosis (ALS) suffer from dysphagia that increases the risk for aspiration, pneumonia and weight loss. Pharyngeal electrical stimulation (PES) is a therapeutic technique that applies electric stimuli to the patient's pharynx in order to improve swallowing based on the principle of cortical plasticity and reorganization. Previous studies have demonstrated positive effects in patients with various neurological diseases.ObjectiveThis study was initiated to investigate the effect of PES on swallowing function in patients with ALS.MethodsIn all, 20 ALS patients with severe dysphagia [characterized by a Penetration Aspiration Scale (PAS) of at least 4 in thin liquid] were randomized to receive either PES for 10 min at 3 consecutive days in addition to Standard Logopaedic Therapy (SLT) or SLT alone. Swallowing function was evaluated by Fiberoptic Endoscopic Evaluation of Swallowing (FEES) at five timepoints: at baseline, 1 day, 4 days, 3 weeks and 3 months after treatment. Primary endpoint was the severity of penetrations or aspirations as classified by PAS. Secondary endpoints were adverse events, dysphagia-related quality of life, Swallowing Quality of Life (SWAL-QOL), Dysphagia Severity Rating Scale (DSRS), residues, leaking, ALS Functional Rating Scale Revised (ALSFRS-R), and the performance in Clinical Evaluation of Swallowing (CES). The trial is registered under the name of 'Pharyngeal Electrical Stimulation in Amyotrophic Lateral Sclerosis' with ClinialTrials.gov, number NCT03481348 (https://clinicaltrials.gov/ct2/show/NCT03481348).ResultsBoth groups combined showed a significant improvement (p = 0.003) of median Total-PAS from 3.6 [interquartile range (IQR) = 2.9-5.0] at baseline to 2.3 (IQR = 1.8-4.0) 1 day after treatment. During subsequent study visits, PAS increased again but remained below baseline. PES and control group did not differ significantly 1 day after intervention (p = 0.32). Similar effects were found in the majority of secondary endpoints.InterpretationThe findings suggest that PES may not provide an additional positive effect on swallowing function in ALS. SLT seems to yield at least short-term positive effects on swallowing function and swallowing-specific life quality in ALS.Registration: ClinialTrials.gov: NCT03481348.

Dataset Information

Pilot trial of inosine to elevate urate levels in amyotrophic lateral sclerosis.

Publications

Pilot trial of inosine to elevate urate levels in amyotrophic lateral sclerosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets