NLP SNP

This is a pilot study in 40 subjects with definite ALS to evaluate the efficacy of valproate and lithium carbonate. After a random assignation of the dual treatment vs. placebo, a follow-up of 20 months will allow to know the clinical and functional evolution so as the status of biomarkers under each treatment.

NCT03204500

Conditions

Amyotrophic Lateral Sclerosis
Amyotrophic Lateral Sclerosis, Sporadic

Interventions

Combination Product: Active treatment with dual therapy
Drug: Placebos

MeSH:Motor Neuron Disease Amyotrophic Lateral Sclerosis Sclerosis

HPO:Abnormal anterior horn cell morphology Amyotrophic lateral sclerosis

In the same year, two Chinese studies showed a synergistic neuroprotective effect of valproate administered with lithium in neuronal cultures and in G93A ALS transgenic models. --- G93A ---

Primary Outcomes

Description: To evaluate the effect of VPA+Li on progression of ALS by measuring functionnal changes from baseline in ALSFRS-R.

Measure: Changes in ALSFRS-R

Time: Every 2 months for 20 months

Secondary Outcomes

Description: Changes from baseline in ALSAQ-5, a brief self-administered quality of life scale.

Measure: Changes in score in ALSAQ-5

Time: Baseline, Month 10, Month 20

Description: DTI biomarkers in corticospinal tract are measured in 6 regions bilaterally

Measure: Changes from baseline in FA (fractional anisotropy)

Time: Baseline and month18

3 GM604 Phase 2A Randomized Double-blind Placebo Controlled Pilot Trial in Amyotrophic Lateral Disease (ALS)

GM604 is an endogenous human embryonic stage neural regulatory and signaling peptide that controls the development, monitoring and correction of the human nervous system. Neurological diseases are multisystem, multifactorial, and single target drugs are ineffective. Genervon's Master Regulators play a significant role in embryonic/fetal nervous system development and are potent disease modification drug candidates modulating many pathways including inflammation, apoptotic, and hypoxia. The study drug is an regulatory peptide with a sequence identical to one of the active sites of human Motoneuronotrophic Factor and is manufactured by solid phase synthesis. Pre-clinical research indicates it to be a neuro-protective agent in animal models of ALS, motorneuron diseases, PD, other neuro-degenerative diseases and stroke. GM604 controls and modulates over many known and significant ALS genes with positive effects interactively and dynamically through multiple pathways, and up to twenty-two biological processes, including neuro-protection, neurogenesis, neural development, neuronal signaling, neural transport, and other processes. GM6 is not a cocktail of drugs, but one master regulator peptide drug that functions through multiple pathways. Genervon hypothesized that studying the biomarkers of protein expressions of these ALS genes such as superoxide dismutase 1 (SOD1) and the protein expression of substances such as tau, neurofilament - heavy (NF-H), Cystatin C which were indications of degeneration of neuron in the CSF collected from ALS patients will provide information of the possible GM604's mechanisms of action in treating ALS. 1. This pilot trial is designed to test proof of principle, i.e. determine if a 2-week IV bolus treatment with this agent can (1) change ALS protein expression (target biomarkers and efficacy biomarkers) after treatment (2) have preliminary effects measures of ALS disease clinical progression. Study Objectives are: 1. To test the safety and tolerability of GM604 in a population of ALS patients. 2. To test for changes in ALS biomarkers before and after treatment. 3. To determine preliminary effects of injections of GM604 on measures of ALS disease biomarkers and clinical progression

NCT01854294

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Drug: GM604
Drug: Placebo comparator

MeSH:Motor Neuron Disease Amyotrophic Lateral Sclerosis

HPO:Abnormal anterior horn cell morphology Amyotrophic lateral sclerosis

In ALS model, SOD1 mice from Jackson Lab stock #G93A were treated with GM604 at 0, 1 and 5 mg/kg. --- G93A ---

Primary Outcomes

Description: Efficacy by percent change in biomarker in the CSF at week 12 from baseline: (a) Efficacy biomarkers (b) Target biomarkers (c) Efficacy/target biomarkers

Measure: Efficacy by percent change in biomarker in th CSF at week 12 from baseline

Time: baseline, week 2, week 12

Description: Safety: 1. adverse event frequency and severity, changes in vital signs, clinical laboratory values. 2. Serious adverse event frequency

Measure: Safety by measuring 1. adverse event frequency and severity, changes in vital signs, clinical laboratory values. 2. Serious adverse event frequency

Time: baseline, week 2, week 12

Description: Tolerability: The ability to complete the first 2 weeks of active treatment in the study

Measure: Tolerability by measuring the ability to complete the first 2 weeks of active treatment in the study

Time: Baseline, week 2, week 12

Secondary Outcomes

Description: Progressive change in ALSFRS-R of each patient determined from the following data points:1) symptom onset, 2) baseline, 3) end of week 2 examination, 4) end of week 6 examination and 5) end of week 12 examination.

Measure: ALSFRS-R (Amyotrophic Laeral Sclerosis Functional Rating Scale - Revised)

Time: Symptom onset, screening, baseline, week 2, week 6, week 12

Description: Progressive change in Forced Vital Capacity (FVC) from the following data points: 1) symptom onset, 2) baseline, 3) end of week 2 examination, 4) end of week 6 examination and 5) end of week 12 examination.

Measure: Forced Vital Capacity (FVC)

Time: Symptom onset, baseline, week 2, week 6, week 12

Measure: Time Up and Go (TUG)

Time: Symptom onset, baseline, week 2, week 6, week 12

Description: Progressive muscle strength change measured by HHD (handheld dynamometry testing score) from the following data points: 1) symptom onset, 2) baseline, 3) end of week 2 examination, 4) end of week 6 examination and 5) end of week 12 examination.

Measure: muscle strength

Time: Symptom onset, baseline, week 2, week 6, week 12

Description: Percentage changes in Biomarkers in blood between baseline and 1) the end of week 1, 2) end of week 2, 3) end of week 6 and 4) end of week 12. Comparing the changes encompassing the entire cohort of 10 subjects.

Measure: Biomarker in blood

Time: baseline, week 2, week 6, week 12

Description: Report all death as mortality rate

Measure: Mortality rate

Time: baseline, week 2, week 6, week 12

Other Outcomes

Description: Secondary analyses may consider a comparison of slopes (change in the rate of decline) for any hint of disease modification using placebo outcomes in patients matched for baseline features from a large database of recent clinical trials by NEALS showing stable rates of decline as historical controls.

Measure: comparison of slopes (change in the rate of decline)of disease progression

Time: Symptom onset, baseline, week 2, week 6, week 12

Description: Secondary analysis to allow a-priori stratification of patients by their symptoms if available predominantly lower motor neuron predominantly upper motor neuron predominantly bulbar

Measure: stratification of patients by symptoms

Time: Symptom onset, baseline, week 2, week 6, week 12

4 Etude de l'Expression Des Micro-RNA Comme Biomarqueur Diagnostic et Pronostic Dans la Sclérose Latérale Amyotrophique

The principal goal is to demonstrate that a specific pattern of microRNA (miRNA) expression can be correlated with the definite diagnostic of Amyotrophic Lateral Sclerosis (ALS). The investigators will use biological sample (from muscle biopsy, Cerebrospinal Fluid (CSF) and blood sample) collected in three control populations: definite ALS patients according to El Escorial diagnostic criterion, control patients without any neurological disease having an orthopedic surgery for shoulder disease, and control patient explored for peripheral neuropathy and myopathy. A second goal will correlate the miRNA pattern to the severity and/or progression rate of the motor neurons define as the progression rate of the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) score/year.

NCT01992029

Conditions

Amyotrophic Lateral Sclerosis
ALS

Interventions

Other: Clinical evaluation
Procedure: Muscular biopsy
Procedure: Lumbar puncture
Procedure: Blood sampling
Other: Neurological assessments
Procedure: Neuro-muscular biopsy and lumbar puncture
Procedure: Muscular biopsy
Procedure: Blood sample
Device: Cervical spinal cord and brain MRI

MeSH:Motor Neuron Disease Amyotrophic Lateral Sclerosis Sclerosis

HPO:Abnormal anterior horn cell morphology Amyotrophic lateral sclerosis

A more recent work on transgenic murine model SOD1 G93A has demonstrated the role of the specific miRNA206 in regulating the re-innervation processes at the neuro-muscular junction. --- G93A ---

Primary Outcomes

Description: miRNA expression pattern in ALS patients compared to control patients.

Measure: miRNA expression

Time: At inclusion (day 0)

Secondary Outcomes

Description: Evolution of miRNA expression level in blood and CSF of ALS patients

Measure: miRNA evolution

Time: 12 months after inclusion

Measure: miRNA expression pattern in different ALS patients compared to control patients predictive of the clinical phenotype and of the progression of the disease.

Time: Day 0 (inclusion)

Description: Difference in diffusivity parameters of MRI between ALS subjects and control groups

Measure: Difference in diffusivity parameters of MRI

Time: At inclusion (Day 0) and 8 month after inclusion

5 Phase II/III Randomized, Placebo-Controlled Trial of Arimoclomol in SOD1 Positive Familial Amyotrophic Lateral Sclerosis (ALS)

The purpose of this study will be to demonstrate the safety, tolerability, and efficacy of arimoclomol in subjects with SOD1 positive familial Amyotrophic Lateral Sclerosis (ALS). This type of ALS is HEREDITARY (runs in families), and at least one other person in the family must have had ALS. Study hypotheses: Arimoclomol, taken at a dose of 200 mg three times daily will improve survival as defined by time to death, tracheostomy or permanent assisted ventilation. In addition, it will be safe and well tolerated in subjects with SOD1 positive familial ALS. Funding Source - FDA-OOPD

NCT00706147

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Drug: Arimoclomol
Drug: Placebo

MeSH:Motor Neuron Disease Amyotrophic Lateral Sclerosis Sclerosis

HPO:Abnormal anterior horn cell morphology Amyotrophic lateral sclerosis

A4V, A4T, C6F, C6G, V7E, L8Q, G10V, G41S, H43R, H48Q, D90V, G93A, D101H, D101Y, L106V, I112M, I112T, R115G, L126X, G127X, A145T, V148G, V148I) or possibly associated with rapidly progressive disease (E21G, G37R, L38V, D76Y, L84F, L84V, N86S, D90A het, G93R, I104F, I113T, L144F, L144S). --- G10V --- --- G41S --- --- H43R --- --- H48Q --- --- D90V --- --- G93A ---

Primary Outcomes

Measure: Time to death, tracheostomy or permanent assisted ventilation will be the primary outcome measure.

Time: 12 months

Secondary Outcomes

Measure: Rate of decline of ALSFRS-R (ALS functional rating scale-revised) over a period of up to 12 months.

Time: 12 months

Measure: Disease progression as measured by the rate of decline of FEV6.

Time: 12 months

Measure: Safety and tolerability of arimoclomol will be evaluated by using vital signs and weight, clinical laboratory measures, physical examination, report of adverse events, and the proportion of subjects completing the study on assigned treatment.

Time: 12 months

6 Impact of the Combined Treatment of Curcumin and Resveratrol Liposomed Polyphenols With Dutasteride on the Clinical Improvement of ALS Patients

Amyotrophic lateral sclerosis (ALS) is a disease of an inflammatory nature, which causes progressive muscle weakness associated with cognitive and behavioural disorders. Pathogenically, it is characterised by loss of oxidative control, excitotoxicity due to excess glutamate and intestinal dysbiosis. In the absence of curative treatment, the aim of the study is to assess the impact at a clinical level of the combination of liposomed polyphenols to improve their effectiveness, with the drug Dutasteride which shows great anti-ALS properties by Molecular Topology methodology. A prospective, longitudinal, mixed, analytical, experimental and double-blind study is proposed, with a population sample of 100 patients distributed randomly in 50 patients in the intervention group who will receive treatment for 6 months, and 50 patients in the control group who will receive a placebo for the same period. The assessment will be at time 0, and at 3 months and 6 months after treatment, with functional, cognitive and behavioural tests, and of the state of inflammation and oxidation; and at time 0 and 6 months, of the intestinal microbiota.

NCT04654689

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Dietary Supplement: Liposomed polyphenols resveratrol and curcumin
Other: Placebo for liposomed resveratrol and curcumin
Dietary Supplement: Isocaloric Diet
Drug: Dutasteride 0.5 mg
Other: Placebo microcrystalline methylcellulose

MeSH:Motor Neuron Disease Amyotrophic Lateral Sclerosis

HPO:Abnormal anterior horn cell morphology Amyotrophic lateral sclerosis

Both mediators promoted the normalization of autophage flow and, more importantly, increased mitochondrial biogenesis in SOD1-G93A mice. --- G93A ---

Primary Outcomes

Description: Maximum value: 48 points; Means better outcome motor variables Minimum value: 0 points

Measure: Revised Amyotrophic Lateral Sclerosis Functional Rating Scale associated with ALS

Time: Time 0

Description: Maximum value: 48 points; Means better outcome motor variables Minimum value: 0 points

Measure: Revised Amyotrophic Lateral Sclerosis Functional Rating Scale associated with ALS

Time: 3 months

Description: Maximum value: 48 points; Means better outcome motor variables Minimum value: 0 points

Measure: Revised Amyotrophic Lateral Sclerosis Functional Rating Scale associated with ALS

Time: 6 months

Description: Motor Variables

Measure: Electromyography

Time: Time 0

Description: Motor Variables

Measure: Electromyography

Time: 3 months

Description: Motor Variables

Measure: Electromyography

Time: 6 months

Description: Motor Variables

Measure: Measurement of forced vital capacity

Time: Time 0

Description: Motor Variables

Measure: Measurement of forced vital capacity

Time: 3 months

Description: Motor Variables

Measure: Measurement of forced vital capacity

Time: 6 months