The Efficacy and Safety of Ornithine Aspartic Acid Granules in NAFLD Against Silymarin Capsules

Study Overview
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Brief Summary
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This is a multicenter, randomized, double-blind, double-dummy, and positive control clinic trial which explores the efficacy and safety of ornithine aspartate granules in the treatment of non-alcoholic fatty liver disease against silymarin capsules. The hypothesis is that the ornithine aspartate granules have similar or better efficacy than the silymarin capsules.

Official Title
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The Efficacy and Safety of Ornithine Aspartic Acid Granules in Non-Alcoholic Fatty Liver Disease Against Silymarin Capsules: a Randomized, Double-Blind, Multicenter Clinical Trial

Conditions
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Non-alcoholic Fatty Liver Disease

Intervention / Treatment
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* Drug: Ornithine aspartate granule
* Drug: Silymarin capsule
* Drug: Silymarin capsule simulant
* Drug: Ornithine aspartate granule simulant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Consistent with NAFLD diagnosis criteria, and during previous one month, the B-mode ultrasonography showed diffuse fatty liver and Fibroscan test showed that CAP value > 248 db/m; 2. During previous one month, serum ALT level was higher than 1.5 times the upper limit of normal. 3. BMI is not more than 30 kg/m2. 4. Voluntary to participate in the research and signed a written informed consent to comply with the trial protocol. Exclusion Criteria: 1. Hereditary metabolic or autoimmune liver disease, hepatotropic and non-hepatotropic virus infection, drug/toxic/alcoholic/biliary liver injury, or any end-stage liver disease; fatty liver disease caused by one of the following reasons: total parenteral nutrition, inflammatory bowel disease, hypothyroidism, Cushing's syndrome, beta-lipoprotein deficiency and some insulin resistance (IR) related syndromes (lipid atrophic diabetes, Mauriac syndrome); 2. Hepatic or extrahepatic malignant tumors; 3. Severe heart failure or renal failure (serum creatinine > 3mg/100mL); 4. Allergic constitution, or allergic to amino acid drugs or to ornithine aspartate and its constituents or to silymarin; 5. ALT or γ-glutamyl transpeptidase (γ-GT) are greater than 5 times the upper limit of normal, or total bilirubin (TBIL) > 51 umol/L.; 6. Confirmed liver cirrhosis or Fibroscan test showed E value > 12.5 kilopascal (KPa); 7. Triglyceride > 5.6mmol/L; 8. Diabetes diagnosed for more than 5 years, combined with current insulin therapy or taking hypoglycemic drugs with poorly controlled condition (HbA1c > 9%). 9. Women who are pregnant, nursing or preparing for pregnancy; 10. Suspected or confirmed excessive drinking (equivalent alcohol amount: male, > 40g/d; female, > 20g/d), or history of drug abuse; 11. Combined use of drugs with liver protection and anti-inflammatory effects, as well as any Chinese patent medicine, Chinese herbal medicine, or health products that may have liver protection or liver damage effects; 12. Taking weight-loss drugs or receiving weight-loss treatment; 13. Situations of inappropriate participation judged by researchers.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ornithine aspartate granule group<br>Patients in this group will be given aspartate ornithine granules (3 g po tid, after three meals) and silymarin capsule simulant (140 mg po bid, before breakfast and dinner). | Drug: Ornithine aspartate granule<br>* Ornithine aspartate granules in the experimental arm.<br>Drug: Silymarin capsule simulant<br>* Silymarin capsule simulant in the experimental arm.<br>|
| Active Comparator: silymarin capsule group<br>Patients in this group will be given silymarin capsule (140 mg po bid, before breakfast and dinner) and aspartate ornithine granules simulant (3 g po tid, after three meals) . | Drug: Silymarin capsule<br>* Silymarin capsules in the active comparator arm.<br>Drug: Ornithine aspartate granule simulant<br>* Ornithine aspartate granule simulant in the active comparator arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients whose controlled attenuation parameter (CAP) value returned to normal or changed by more than 10% |  | Assessed at 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The changed degree of quality-of-life measured by the Chronic Liver Disease Questionnaire (CLDQ)-NAFLD/NASH |  | Assessed at 4 weeks, 12 weeks, and 24 weeks | 
| The proportion of patients whose alanine aminotransferase (ALT) level returned to normal or changed by more than 50% |  | Assessed at 4 weeks, 12 weeks, and 24 weeks |