Explore Neuroprotective Effect of Lipoic Acid in Amyotrophic Lateral Sclerosis

Study Overview
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Brief Summary
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In this proposed study, the investigators will evaluate the safety and efficacy of lipoic acid in treatment of Amyotrophic lateral sclerosis (ALS). The study will recruit 150 AD patients, and then these patients will be randomized to lipoic acid group or control group (75 patients per arm) for 6 courses for about 5 months. Clinical assessment will be done at screen/baseline, 3th course and 6th course. The specific aims are to compare lipoic acid versus control on: motor function and disease progression. During the study period, clinical effect index will be recorded, including bulbar function, motor function, respiratory function, and safety index including blood and urine routine, liver and kidney function, coagulation function.

Detailed Description
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In this proposed study, the investigators will evaluate the safety and efficacy of Lipoic acid in treatment of ALS. The study will recruit 150 ALS patients, then these patients will be randomized to lipoic acid group or control group (75 patients per arm) for 6 courses for about 5 months. Clinical efficacy and safety assessment will be done at screen/baseline, 3th course and 6th course. The specific aims are to compare lipoic acid versus placebo on: (1) Lipoic acid could improve the motor function, delay the disease progression and extend survival time in patients with ALS, measured by the ALSFRS-R Scale, ROADS Scale, upper motor neuron Scale, Muscle strength Scale and Electromyography; (2) Lung function will be collected to prove the hypothesis lipoic acid may help respiratory function. (3) Safety index including blood and urine routine, liver and kidney function, coagulation index will be recorded.

Official Title
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Randomized, Parallel Safety and Efficacy Study of Lipoic Acid in Patients With Amyotrophic Lateral Sclerosis

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: lipoic acid group
* Drug: control group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age range from 20 to 75 (including 20 and 75 years old), regardless of ethnic group or gender; The subjects should meet the diagnostic criteria for ALS by El Escorial revised criteria: Definite ALS, Probable ALS and Probable, laboratory-supported ALS. ALS Functional Rating Scale-Revised (ALSFRS-R 12 items) each item score ≥2 points; The onset (the symptoms of limbs weakness, muscle atrophy or bulbar involvement ) of the disease is less than 2 years Baseline breath function: Forced Vital Capacity≥70% . Disease Progression Rate FS=(48- ALSFRS-R at time of diagnosis)/duration from onset to diagnosis (month), progression rate FS≤1; Exclusion Criteria: Combined with one of cerebrovascular disease, spinal cord disease, spinal muscular atrophy, juvenile myoatrophy of distal upper extremity, multifocal motor neuropathy, Kennedy disease, epilepsy, etc; Severe renal insufficiency: creatinine clearance rate <30 mL/min (Cockcroft-Gault formula, urea nitrogen and (or) blood creatinine> 1.5 times the upper limit of normal, or other known severe renal insufficiency diseases; Severe liver damage: ALT, AST> 3 times the upper limit of normal, or other known liver diseases such as acute and chronic hepatitis, cirrhosis, etc.; Obvious tachycardia or bradycardia; patients with acute myocardial infarction or interventional therapy in the past 6 months (patients with grade III-IV according to NYHA classification); Combined with malignant tumor, blood, digestion or other serious diseases; Female patients during pregnancy and lactation; Participated in other clinical trials within 30 days before randomization, or are participating in other clinical trials;

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: lipoic acid group<br>The patients will take lipoic acid by intravenous. At the same time, the patients will take take riluzole tablets orally everyday. | Drug: lipoic acid group<br>* The patients will take lipoic acid for 6 course, the first course of treatment is 14 days with 14 days of rest, and the following course is the first for 10 days, with 14 days interval.The patients will use 600mg domestic lipoic acid in 250ml normal saline by intravenous, once a day. At the same time, the patients will take domestic riluzole tablets 50mg orally, twice a day.<br>|
| Experimental: control group<br>The patients will take riluzole tablets orally everyday. | Drug: control group<br>* The patients will take domestic riluzole tablets 50mg orally, twice a day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change of Amyotrophic lateral sclerosis Function Rate Scale-Revised (ALSFRS-R) | The Amyotrophic lateral sclerosis Function Rate Scale-Revised (ALSFRS-R) will be performed to test the motor function of patients at the enrollment, 3th course and 6th course . The score ranges from 0 to 48#and higher scores represent a better motor function. | change from baseline to 11th week& 21th week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change of Rasch Overall ALS Disability Scale (ROADS) | Rasch Overall ALS Disability Scale (ROADS) will be performed to test the motor function of patients at the enrollment, 3th course and 6th course . The score ranges from 0 to 56#and higher scores represent a better motor function. | change from baseline to 11th week& 21th week | 
| change of Upper motor neuron scale (UMNS) | Upper motor neuron scale(UMNS) will be performed to test the motor function of patients at the enrollment, 3th course and 6th course . The score ranges from 0 to 33. | change from baseline to 11th week& 21th week | 
| change of Muscle strength scale | Muscle strength scale will be performed to test the muscle strength of patients at the enrollment, 3th course and 6th course. Higher scores represent a better muscle strength. | change from baseline to 11th week& 21th week | 
| change of Pulmonary Forced Vital Capacity (PFVC) | Pulmonary Forced Vital Capacity (PFVC) will be performed to test the breath function of patients at the enrollment, 3th course and 6th course. Higher scores represent a better pulmonary function. | change from baseline to 11th week& 21th week | 
| change of Motor Neuron Disease Electromyography | Motor Neuron Disease Electromyography will be performed to test the electrical activity of muscles of patients at the enrollment, 3th course and 6th course . | change from baseline EMG to 21th week |