Dataset Information

Interleukin-1 Antagonist Anakinra in Amyotrophic Lateral Sclerosis--A Pilot Study.

ABSTRACT: Preclinical studies show that blocking Interleukin-1 (IL-1) retards the progression of Amyotrophic Lateral Sclerosis (ALS). We assessed the safety of Anakinra (ANA), an IL-1 receptor antagonist, in ALS patients. In a single arm pilot study we treated 17 ALS patients with ANA (100 mg) daily for one year. We selected patients with dominant or exclusive lower motor neuron degeneration (LMND) presentation, as peripheral nerves may be more accessible to the drug. Our primary endpoint was safety and tolerability. Secondary endpoints included measuring disease progression with the revised ALS functional rating scale (ALSFRSr). We also quantified serum inflammatory markers. For comparison, we generated a historical cohort of 47 patients that fit the criteria for enrollment, disease characteristics and rate of progression of the study group. Only mild adverse events occurred in ALS patients treated with ANA. Notably, we observed lower levels of cytokines and the inflammatory marker fibrinogen during the first 24 weeks of treatment. Despite of this, we could not detect a significant reduction in disease progression during the same period in patients treated with ANA compared to controls as measured by the ALSFRSr. In the second part of the treatment period we observed an increase in serum inflammatory markers. Sixteen out of the 17 patients (94%) developed antibodies against ANA. This study showed that blocking IL-1 is safe in patients with ALS. Further trials should test whether targeting IL-1 more efficiently can help treating this devastating disease.ClinicalTrials.gov NCT01277315.

SUBMITTER: Maier A

PROVIDER: S-EPMC4596620 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Interleukin-1 Antagonist Anakinra in Amyotrophic Lateral Sclerosis--A Pilot Study.

Maier André A Deigendesch Nikolaus N Müller Kathrin K Weishaupt Jochen H JH Krannich Alexander A Röhle Robert R Meissner Felix F Molawi Kaaweh K Münch Christoph C Holm Teresa T Meyer Robert R Meyer Thomas T Zychlinsky Arturo A

PloS one 20151007 10

<h4>Unlabelled</h4>Preclinical studies show that blocking Interleukin-1 (IL-1) retards the progression of Amyotrophic Lateral Sclerosis (ALS). We assessed the safety of Anakinra (ANA), an IL-1 receptor antagonist, in ALS patients. In a single arm pilot study we treated 17 ALS patients with ANA (100 mg) daily for one year. We selected patients with dominant or exclusive lower motor neuron degeneration (LMND) presentation, as peripheral nerves may be more accessible to the drug. Our primary endpoi ...[more]

PMID: 26444282

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.

Project description:Background:Oligodendrocytes (OGs) provide metabolic support to motor neurons (MNs) and are implicated in the pathophysiology of amyotrophic lateral sclerosis (ALS). MD1003, or high-dose Pharmaceutical grade Biotin (hdPB), may improve disability in progressive multiple sclerosis patients via augmentation of OG or MN energy levels. Here, we assessed the safety and efficacy of MD1003 in ALS patients. Methods:This single centre, randomised, double-blind, placebo-controlled trial included patients aged 25-80 years with probable or definite ALS. Patients were assigned (2:1), using a computer-generated randomisation list, to receive oral MD1003 (300 mg/day) or placebo treatment for 24 weeks. The primary outcome, safety, was analysed in all patients who received at least one dose of study drug. This study, registered with ClinicalTrials.gov, NCT03114215, has been completed. Findings:Between June and December 2016, 30 patients were enrolled (MD1003, n = 20; placebo, n = 10). Baseline characteristics were representative of the ALS population. MD1003 and placebo groups were not well balanced at screening, with the MD1003-treated group having a higher rate of ALSFRS-R decline prior to screening versus placebo (-6·0 IQR [-8·5, -5·0] vs. -5·0 IQR [-5·0, -3·0]) and a predominance of ALS with upper limb onset compared to placebo (35% vs. 10%). MD1003 had a favourable safety profile and was well tolerated. The occurrence of adverse events was similar in both groups (60%). Two deaths occurred in the MD1003 group versus 1 in the placebo group. ALSFRS-R median change from baseline to month 6 was not significantly different between the two groups (p = 0·49); the mean difference between groups was -1·6 (SEM=3·3). Interpretation:MD1003 treatment was safe and well tolerated. It was not possible to establish MD1003 efficacy in this relatively small study. Given the favourable safety profile of MD1003 and an imbalance between treatment groups favouring placebo, additional, larger studies in ALS are warranted. Funding:MedDay Pharmaceuticals.

Dataset Information

Interleukin-1 Antagonist Anakinra in Amyotrophic Lateral Sclerosis--A Pilot Study.

Publications

Interleukin-1 Antagonist Anakinra in Amyotrophic Lateral Sclerosis--A Pilot Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets