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

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

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.

Study Overview

• Status: Completed
• Conditions: Non-alcoholic Fatty Liver Disease
• Intervention / Treatment: Drug: Ornithine aspartate granule; Drug: Silymarin capsule simulant; Drug: Silymarin capsule; Drug: Ornithine aspartate granule simulant

• Study Type: Interventional
• Enrollment (Actual): 237
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200092
      • Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ornithine aspartate granule group; 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; Ornithine aspartate granules in the experimental arm.; Drug: Silymarin capsule simulant; Silymarin capsule simulant in the experimental arm.
Active Comparator: silymarin capsule group; 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; Silymarin capsules in the active comparator arm.; Drug: Ornithine aspartate granule simulant; Ornithine aspartate granule simulant in the active comparator arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The changed amount of blood ammonia	An exploratory indicator	Assessed at 4 weeks, 12 weeks, and 24 weeks
The changed amount of body fat	An exploratory indicator of body composition analysis	Assessed at 4 weeks, 12 weeks, and 24 weeks
The changed amount of body fat proportion	An exploratory indicator of body composition analysis	Assessed at 4 weeks, 12 weeks, and 24 weeks
The changed amount of muscle mass	An exploratory indicator of body composition analysis	Assessed at 4 weeks, 12 weeks, and 24 weeks

Collaborators and Investigators

• Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
• Collaborators: Beijing YouAn Hospital; Beijing Ditan Hospital; First Affiliated Hospital, Sun Yat-Sen University; Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
• Investigators: Principal Investigator: Jian G Fan, PHD, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2019
• Primary Completion (Actual): December 18, 2022
• Study Completion (Actual): December 20, 2022

Study Registration Dates

• First Submitted: August 24, 2021
• First Submitted That Met QC Criteria: September 3, 2021
• First Posted (Actual): September 13, 2021

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pyrans; Benzopyrans; Flavonoids; Chromones; Flavonolignans; Silymarin
• Other Study ID Numbers: XH-19-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No