SNPMiner Trials by Shray Alag


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Report for Mutation G93A

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 5 clinical trials

Clinical Trials


1 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 Amyotrophic Lateral Sclerosis 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

2 Phase 1 Open Label Study of Zinc Therapy in ALS Patients

The purpose of this study is to determine the safety of Zinc given at 90mg/d in conjunction with 2mg/d of copper in ALS patients.

NCT01259050 Amyotrophic Lateral Sclerosis Drug: Zinc and Copper
MeSH: Motor Neuron Disease Amyotrophic Lateral Sclerosis
HPO: Abnormal anterior horn cell morphology Amyotrophic lateral sclerosis

Previous studies have shown that in ALS mutant G93A SOD transgenic mice, actual zinc supplementation delayed death. --- G93A ---

Primary Outcomes

Measure: To evaluate the safety of high doses of zinc in patients with ALS

Time: 1 year

Secondary Outcomes

Measure: Measure levels of BMAA in blood and urine to determine if there is a decline in these levels over the course of treatment

Time: 1 year

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 Amyotrophic Lateral Sclerosis 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

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: 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 Amyotrophic Lateral Sclerosis ALS 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 A Randomized Clinical Trial, Double Blind, Placebo-controlled of Lithium and Valproate in Amyotrophic Lateral Sclerosis.

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 Amyotrophic Lateral Sclerosis Amyotrophic Lateral Sclerosis, Sporadic 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


HPO Nodes


Abnormal anterior horn cell morphology
Genes 18
ASAH1 TFG CPLANE1 CEP126 DCTN1 IGHMBP2 PRPH SMN1 SMN2 VRK1 SMN1 ATXN3 UBA1 SOD1 SMN1 NEFH SETX GLE1
Amyotrophic lateral sclerosis
Genes 77
MATR3 TREM2 VCP FUS PRPH ANXA11 ALS2 C9ORF72 HNRNPA1 PRPH PFN1 FUS UBQLN2 SQSTM1 ATXN2 MATR3 TBK1 CHMP2B SIGMAR1 PON1 OPTN MAPT MATR3 ANG VCP DAO ERBB4 SQSTM1 SPG11 NEFH EPHA4 CCNF ANG TARDBP DCTN1 PON2 SOD1 ANXA11 UBQLN2 GLT8D1 FIG4 OPTN DCTN1 TARDBP CHMP2B VAPB SIGMAR1 HNRNPA1 CFAP410 PFN1 PSEN1 HNRNPA1 SOD1 SPG11 C9ORF72 ALS2 TRPM7 ERBB4 CHCHD10 KIF5A VAPB PON3 FIG4 GLE1 NEK1 CHCHD10 PPARGC1A TUBA4A VCP UNC13A TBK1 VCP HNRNPA2B1 TAF15 FUS NEFH SETX