Active clinical trials for "Motor Neuron Disease"

Amyotrophic lateral sclerosis (ALS) is a rare neuromuscular disease that occurs in adults. It is characterized by a progressive degeneration of the first and second motor neurons leading to muscle failure. In its spinal form, ALS manifests by a progressive worsening of limb involvement, whereas the bulbar form presents with swallowing disorders, dysarthria and feeding difficulties. Respiratory impairment is the most serious feature of ALS. Phrenic nerve damage causes diaphragmatic weakness, which inevitably leads to chronic restrictive respiratory failure. At the stage of symptomatic nocturnal or diurnal alveolar hypoventilation, non-invasive ventilation (NIV) prolongs survival while improving quality of life by relieving respiratory symptoms. The indication for the initiation of NIV is based on the appearance of respiratory symptoms but also on the demonstration of diaphragmatic insufficiency. A quarterly follow-up of diaphragmatic function has been recommended by the French Health Authority since 2006. It is based on functional respiratory explorations (VC in sitting and lying position, measurement of maximal inspiratory pressure) and screening for diurnal or nocturnal hypoventilation with the measurement of PaCO2 or the nocturnal recording of SpO2. Access to these examinations remains limited and they are sometimes complex to perform (in particular issues with mouth occlusion during respiratory manoeuvres in case of bulbar damage). Thus, only 60% of patients undergo a complete evaluation. Moreover, these explorations are only late markers of diaphragmatic dysfunction, and it has recently been shown that they do not correlate with histological diaphragmatic amyotrophy. The development of new, reliable, and easily available tools for the evaluation of diaphragmatic function, and that are capable of detecting diaphragmatic insufficiency early in the course of the disease, are therefore necessary. Such tools would make it easier to implement NIV at the optimal time, preventing episodes of acute respiratory distress. Recently, diaphragmatic ultrasound has appeared in the ICU as a new tool for assessing diaphragmatic function. It has the advantage of being highly available, inexpensive, non-irradiating, quick to perform, reproducible and very sensitive and specific for the diagnosis of diaphragmatic dysfunction. In ALS, few studies have investigated the contribution of ultrasound for the diagnosis or follow-up of diaphragmatic dysfunction. In addition, no study so far has compared diaphragmatic ultrasound to complete pulmonary function test (PFT) data or to direct measurement of diaphragmatic pressure (Pdi). Very few publications report the how the diaphragm changes on ultrasound imaging during the disease. Moreover, these studies do not analyse the interest of diaphragmatic ultrasound in the prediction of progression towards respiratory failure with respiratory support, or death. Finally, these studies use different ultrasound measurements of the diaphragm (stroke, thickness, thickening fraction, and thickening fraction ratio, among others) rather than a simple, consensual parameter. The aim of this study is to describe the evolution of diaphragmatic ultrasound parameters, to identify the parameter that best correlates with other respiratory measures (PFT, PaCO2, nocturnal oximetry) and to determine the prognostic value of diaphragmatic ultrasound in predicting the initiation of NIV or death at 6 and 12 months.

RNALS is a multicentre, transversal, diagnostic and non-interventional study carried out in ALS reference centers; in order to identify a diagnostic signature for Amyotrophic Lateral Sclerosis by analyzing of coding and non-coding RNA contained in patients saliva. The study population consists of patients with definite or probable amyotrophic lateral sclerosis (ALS) according to the El Escorial criteria ("ALS Subjects" group) and subjects with no neurological history (Control group). The control group will be made up of caregivers of patients with ALS, and caregivers of patients with a pathology other than ALS. The ALS patients concerned by the study already benefit from routine medical care in ALS expert centers in France. The patients concerned by the study will be managed without modification of the care pathway, nor modification of the therapeutic indications, nor modification of the diagnostic or follow-up examinations necessary according to the context, which are carried out according to the recommendations of the HAS, CNGOF.

Patients with motor neurone disease typically experience relentless motor decline and die within three years of symptom onset from respiratory muscle weakness. There are currently no effective therapies and the discovery of novel therapies is hampered by the lack of a sensitive disease biomarker. Consequently, there is a huge drive to discover novel biomarkers, which can reliably track disease progression over time. These can then be incorporated into clinical drug trials to expedite effective drug discovery. Muscle fasciculations represent the hyperexcitability of diseased motor neurons and are almost universally present from the early stages of MND. We predict that the site, frequency and shape of fasciculations might provide a sensitive measure of disease progression in an individual. We have been conducting a 12-month longitudinal study of 25 patients, performing high-density surface EMG every two months. We have validated an automated technique to process these large data sets. Ultrasound is widely used in clinical medicine to assess anatomical structure in a safe and non-invasive way. Dr Emma Hodson-Tole (Manchester Metropolitan University) and her group have been applying this to the analysis of fasciculations in healthy individuals and patients with MND. This collaborative project will explore combining these two techniques simultaneously in patients with motor neuron disease and control subjects. The goal is to explore the nature of electro-mechanical coupling related to fasciculations and to determine whether any of these properties are pathophysiological. This would complement other studies from our two groups, investigating the natural history and potential utility of fasciculations as a biomarker of motor neuron health in MND.

The EyeControl device is an eye movement-based communication device in the form of wearable glasses with connected infrared cam-era that tracks the pupil and translates blinks and movements into commands.This study is aimed to demonstrate the safety and feasibility of the EyeControl device in healthy volunteers, and ALS patients in early stages.

To evaluate if transcranial magnetic stimulation can be used as a biomarker in Amyotrophic Lateral sclerosis (ALS).

Anti alfa-3 and alfa-7 ganglionic cholinergic receptors (anti-AChRs) antibodies (Abs) plasma removal by plasmapheresis (1,2) acutely improved dysautonomia symptoms in case reports with Pure Autonomic Failure (PAF) (3). We shall assess the prevalence of anti-AChRs Ab and the relationship among Ab titer, cardiovascular autonomic profile and symptoms in neurodegenerative diseases characterized by similar dysautonomia symptoms such as PAF, Amyotrophic Lateral Sclerosis (ALS) and Postural Orthostatic Tachycardia Syndrome (POTS) (4). Ab positive patients will undergo selective immunoabsorption once a week up to achievement of Ab titer lower than 65% of baseline followed by immunosuppressive therapy with prednisone. Both Ab positive and negative groups will undergo anti-AChR Abs, autonomic profile and dysautonomia symptoms assessment, every 4 months up to 3 years. Evidence of correlation among reduced Ab titer and autonomic profile and symptoms improvement may result in new effective therapy.

The first questions asked by patients with a new diagnosis of Amyotrophic Lateral Sclerosis (ALS) often include: "Does exercise help slow the progression of the disease?", "Is there any harm in exercising?", or "What type of exercise (endurance or resistance) is most appropriate?" At this time, however, there is a lack of answers for people who suffer from an illness that affects their strength above all else. Yet the beneficial effects of exercise in both healthy people as well as people with other diseases have been extensively studied and resulted in recommendations about the types of exercise that are beneficial. In this study the investigators will ask participants with ALS to exercise in one of three ways: weightlifting (resistance exercise), stationary bicycling (endurance exercise), and range of motion exercise (the current "standard of care" for ALS patients). The investigators will use several different types of tests to determine whether one type of exercise is tolerated better and is safer than another. The investigators will also collect information about how the body responds to exercise in ALS. This study will help in the development of a larger national study to understand how exercise can be combined with other treatments to potentially improve strength and alter the course of the disease.

Consistent data suggest that neuromuscular transmission is impaired in ALS patients. Neuromuscular junctions dysfunction may appear very early in the disease, as shown by data in animal models. The pathogenesis of this neuromuscular transmission impairment is unknown. Nogo A isoform, a possible marker of the disease over-expressed in skeletal muscle of ALS patients, can be involved. We will characterize the pathophysiological mechanisms implicated using a complete study of the structure and function of the NMJ on muscle biopsies, in a group of 20 ALS patients compared to 10 controls.

This study evaluated the influence of a tailored aerobic exercise protocol on the functional outcome in ALS patients. In addition, the investigators compare some CPET variables collected during exercise testing in both groups.

This is a 6-month double blind randomized 2:1 placebo-controlled study with two arms (placebo, biotin 300 mg/day). The study will be followed by a 6-month extension phase during which all patients will receive biotin 300 mg/day.