View clinical trials related to Amyotrophic Lateral Sclerosis.
Filter by:Recently two staging systems have been proposed for amyotrophic lateral sclerosis (ALS), based on clinical milestones The King's college clinical staging system (1) and ALS Milano-Torino Staging (ALS-MITOS) (2). Further research to validate and develop an accurate staging system in different populations will improve our understanding of its pathogenesis, disease activity and progression. General objective : To validate the two previously proposed staging system and to test the interest of considering Neurofilament biomarkers in these systems. Specific objectives: 1) To validate the two classification systems in an independent cohort of patients with ALS followed-up in the ALS expert center of Limoges (France) 2) To assess the interest of Nf biomarkers to predict neurological decline
The primary objective of this study is to evaluate the efficacy of tofersen in presymptomatic adult carriers of a superoxide dismutase 1 (SOD1) mutation with elevated neurofilament (NF). The secondary objectives of this study are to evaluate the safety and tolerability tofersen and to evaluate the effect of tofersen on pharmacodynamics (PD)/treatment response biomarkers when initiated prior to versus at the time of emergence of clinically manifest amyotrophic lateral sclerosis (ALS).
Hyperkinetic movement disorders in patients with diseases of motor neurons will be studied. Patients with spinal muscular atrophy (SMA) and motor neuron disease patients will be studied. Involuntary movements will be video recorded and accelerometry with electromyography (EMG) will be recorded in a subset of patients. Hyperkinetic involuntary movements studied will be tremor and minipolymyoclonus. Tremor is defined as involuntary, rhythmic, oscillatory movements of a body part, and minipolymyoclonus are intermittent and irregular movements, with amplitudes sufficient to produce visible movements of the joints. Hyperkinetic movement disorders may be of central or peripheral origin and using accelerometry with EMG may help distinguish the two mechanisms. In patients with SMA the investigators will explore the effect of Nusinersen treatment on phenomenology and amplitude of tremor and minipolymyoclonus. Aims: To explore the prevalence and phenomenology of hyperkinetic movement disorders in patients with MND and SMA and to study the underlying pathological mechanisms with the use of accelerometry and EMG. To explore the effect of Nusinersen treatment on phenomenology and amplitude of involuntary movements. Hypotheses: Based on clinical observations the investigators believe it will proven that hyperkinetic movement disorders are common in patients with disease of motor neurons. The investigators hypothesize that hyperkinetic movement disorders in MND and SMA patients are of peripheral origin, being caused by uneven graduation of contraction in the wasted muscles with large motor units being active with no sufficient previous recruitment of small units to smooth contraction of large motor units. If tremor and minipolymyoclonus in SMA are due to the activation of enlarged motor units which are caused by reinnervation of muscle fibers, the treatment with Nusinersen will increase the amplitude of tremor and minipolymyoclonus. Methods: Presence, quality, and regularity of hyperkinetic movement disorders will be defined using clinical examination, accelerometry and EMG. Hyperkinetic movements will be classified as minipolymyoclonus or tremor. In patients with SMA, the measurements will be repeated 6-12 months after initiation of treatment with Nusinersen.
Weight loss is a known negative prognostic factor in amyotrophic lateral sclerosis (ALS). One potential mechanism of weight loss in ALS is a disturbance of the mitochondrial complex I which causes an energy deficit in affected cells. Over the last years, various interventional studies targeting the energy deficit in ALS yielded promising results; however,it is still unclear which kind of nutrition or nutritional supplement is most beneficial. Ketone bodies represent a logical therapeutic option in ALS as ketone bodies are an extremely high-energetic substrate which yields the double amount of adenosine triphosphate (ATP) per mole compared to glucose. The human liver is able to synthesize ketone bodies (beta-hydroxybutyrate, acetone, and aceto-acetate) from fat in times of glucose shortage, for example after a prolonged period of fasting. This metabolic shift is the underlying principle of the ketogenic diet, a carbohydrate-free, fat-rich diet which has been successfully tested in other neurodegenerative diseases such as Alzheimer's and Parkinson's disease. In the ALS mouse model, a ketogenic diet was associated with a slower decline of motor function. However, a ketogenic diet is difficult to implement in ALS as it requires a long-term change of eating habits, which is difficult to achieve due to progressive dysphagia, fast worsening of general condition, and limited survival. Therefore, the direct administration of ketone bodies yields a more realistic alternative in ALS as it is easy to apply and allows to maintain the usual eating habits. In this study, we hypothesize that the administration of 3 x 10 g beta hydroxybutyrate ester per day (in addition to normal food intake and the standard medication of 2 x 50 mg riluzole) slows down disease progression as measured by neurofilament light chains (NfL) in serum after 6 months compared to placebo. Power calculation relies on the results of the lipids and calories for ALS (LIPCAL-ALS) study which tested the effect of a high-caloric fatty nutritional supplement in ALS. The study revealed that NfL serum values declined significantly in the intervention group while remaining stable in the placebo group over the course of the study. Assuming a similar effect size for ketone bodies, we calculated that 76 patients had to be included in the current trial.
The aim of this project is to analyze the macrophage transcriptome and protein markers of Amyotrophic Lateral Sclerosis (ALS) patients compared to controls (non-affected individuals, patients with other motor impairments) and asymptomatic ALS gene carriers, to find new pathways for therapeutic targets and disease biomarkers.
The purpose of this study is to investigate if a person with weakness or paralysis in one or both arms, can use the NuroSleeve combined powered arm brace (orthosis) and muscle stimulation system to help restore movement in one arm sufficient to perform daily activities. This study could lead to the development of a product that could allow people with arm weakness or arm paralysis to use the NuroSleeve and similar devices to improve arm health and independent function.
The measurement of the facial deformation according to the body posture will be conducted by 3D scanning for each posture after marking the landmarks on the face. A 3D scan of the face will be conducted for 1 minute in a static state for the sitting posture to be used as a reference, the supine posture to gaze at the ceiling while lying down correctly, and the lateral posture to the side with the upper body facing left. Healthy volunteer and ALS with bulbar palsy participants will be asked to keep their mouths closed gently while the 3D scan was being processed. A post-processing of the 3D face scan data will be conducted to analyze facial deformation by the body postures. A facial deformation will be analyzed by measuring the amount of change in position for each reference point after aligning and rotating the facial data on the same basis. The relative ratio of the amount of position change to the size of the face will be analyzed. The present study will analyze the effect of the body posture on the position changes of the landmarks.
The primary purpose of this study is to evaluate the efficacy of ION363 on clinical function and survival in carriers of fused in sarcoma mutations with amyotrophic lateral sclerosis (FUS-ALS).
RT001-014 is a Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Assess Efficacy, Long Term Safety and Tolerability of RT001 in Subjects with Amyotrophic Lateral Sclerosis
This study consists of a phase 1 part and a phase 2 part. Phase 1 part: This is a phase 1, open-label, multicenter, dose escalation study to evaluate the safety and tolerability of bosutinib to determine the maximum tolerated dose(MTD) and a recommended phase 2 dose (RP2D) of bosutinib for treatment of ALS patients. Also, efficacy will be evaluated exploratory. Phase 2 part: This is an open label, multicenter, phase 2 part whose purpose is to evaluate the efficacy exploratorily and the long-term (for 24 weeks) safety of bosutinib for the treatment of ALS patients.