Clinical Trials Using HepatoKeeper Herbal Essentials to Treat Non-alcoholic Fatty Liver Disease and Metabolic Factors

A Clinical Trial Using Ganwei (HepatoKeeper) Herbal Essentials to Treat Non-Alcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease globally, with an estimated prevalence of approximately 15 to 30%. The incidence of NAFLD is even higher, reaching up to 58%, in individuals who are overweight or obese. The pathogenesis of NAFLD is complex and not fully understood. The metabolism of carbohydrates contributes to the development of NAFLD, as it increases the enzymatic activity of lipid synthesis in the liver, depleting adenosine triphosphate (ATP) rapidly and causing stress on mitochondria and endoplasmic reticulum. The multifunctional protein Glycine N-methyltransferase (GNMT) plays a regulatory role in liver carbohydrate metabolism, and its expression is downregulated in the liver tissues of NAFLD.

While weight loss and lifestyle adjustments are helpful in controlling NAFLD, effective pharmacological or healthcare interventions for NAFLD patients are currently lacking. Insulin resistance is crucial in the pathogenesis of NAFLD, suggesting that drugs improving insulin sensitivity, such as metformin, might have therapeutic effects. However, recent large-scale clinical trial results have not supported this hypothesis. Investigators propose that the mitochondrial inhibitory effects of metformin may be related to this discrepancy, and the negative effects may be reversed through food containing substances promoting GNMT gene expression, such as Ganwei (as know as "HepatoKeeper"). Preliminary animal experiments also show that the combined use of metformin and GNMT enhancers effectively eliminates liver lipid droplet accumulation and improves liver inflammation in a NAFLD mouse model, surpassing the effects of either drug used alone.

Based on these findings, our team designed the medication treatment group for this clinical trial, aiming to investigate whether the combination of Ganwei and metformin produces a synergistic effect in humans. Ganwei compound herbal extract capsules contain extracts from natural foods such as Schisandra chinensis, Paeonia lactiflora, and Punica granatum. Among them, Paeonia lactiflora is known to contain components that enhance GNMT expression. Animal and cell experiments have demonstrated its potential for repairing liver damage and inflammation. This trial aims to assess the impact of orally administering Ganwei compound herbal extract capsules on participants and evaluate its effects on fatty liver, liver fibrosis, and metabolic indicators.

Study Overview

• Status: Completed
• Conditions: Non-alcoholic Fatty Liver Disease; Liver Fibrosis; Liver Injury
• Intervention / Treatment: Drug: Metformin; Drug: Placebo; Drug: Ganwei

Detailed Description

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease globally, with an estimated prevalence of approximately 15 to 30%. The incidence of NAFLD is even higher, reaching up to 58%, in individuals who are overweight or obese (Schwenger, 2014). With the Westernization of diets and insufficient physical activity, the prevalence of obesity, diabetes, and hyperlipidemia has been increasing in Taiwan in recent years, contributing to the gradual rise in the prevalence of NAFLD. NAFLD is strongly associated with metabolic syndrome, cardiovascular diseases, insulin resistance, and may progress to hepatitis, liver fibrosis, and even cirrhosis (Fazel, 2016; Amr, 2020).

The pathogenesis of NAFLD is complex and not fully understood. Current understanding suggests that environmental factors such as diet, exercise, obesity, gut microbiota, and genetics play a role in the development of NAFLD. The liver, responsible for metabolizing major substances including carbohydrates and fatty acids, becomes overwhelmed, leading to the production of toxic lipids. Disruptions in lipid metabolism, inhibition of mitochondrial function, and impaired export of triglycerides from liver cells contribute to the accumulation of lipids within the liver. Insulin resistance further exacerbates this process. Additionally, lipid alterations in liver cells increase oxidative stress and activate cell signaling, triggering immune responses that damage liver cells and contribute to the development of fatty liver inflammation, fibrosis, and potentially liver cancer (Fazel, 2016; Amr, 2020).

The metabolism of carbohydrates also contributes to NAFLD, as it increases the enzymatic activity of lipid synthesis in the liver, depleting adenosine triphosphate (ATP) rapidly and causing stress on mitochondria and endoplasmic reticulum. This results in liver cell necrosis, contributing to the development of NAFLD. The multifunctional protein Glycine N-methyltransferase (GNMT) plays a regulatory role in liver carbohydrate metabolism, and its expression is downregulated in the liver tissues of NAFLD (Liao, 2012).

While weight loss and lifestyle adjustments are helpful in controlling NAFLD, effective pharmacological or healthcare interventions for NAFLD patients are currently lacking (Julien et al., 2019; Mary et al., 2020). Insulin resistance is crucial in the pathogenesis of NAFLD, suggesting that drugs improving insulin sensitivity, such as metformin, might have therapeutic effects. However, recent large-scale clinical trial results have not supported this hypothesis. Investigators propose that the mitochondrial inhibitory effects of metformin may be related to this discrepancy, and the negative effects may be reversed through food containing substances promoting GNMT gene expression, such as Ganwei (as know as "HepatoKeeper"). Preliminary animal experiments also show that the combined use of metformin and GNMT enhancers effectively eliminates liver lipid droplet accumulation and improves liver inflammation in a NAFLD mouse model, surpassing the effects of either drug used alone.

Based on these findings, our team designed the medication treatment group for this clinical trial, aiming to investigate whether the combination of Ganwei and metformin produces a synergistic effect in humans. Ganwei compound herbal extract capsules contain extracts from natural foods such as Schisandra chinensis, Paeonia lactiflora, and Punica granatum. Among them, Paeonia lactiflora is known to contain components that enhance GNMT expression (Kyu-Han et al., 2020; Rajni et al., 2019). Animal and cell experiments have demonstrated its potential for repairing liver damage and inflammation. This trial aims to assess the impact of orally administering Ganwei compound herbal extract capsules on participants and evaluate its effects on fatty liver, liver fibrosis, and metabolic indicators.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 103212
    • Taipei City Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Must be willing to participate in the study and provide written informed consent.
• Male and female adults ≥20 and <80 years of age.

• Suspected or confirmed diagnosis of NAFLD:

  • Fibroscan with CAP ≥220 dB/m
  • Criteria for diagnosing fatty liver: Abdominal ultrasound reveals differences in liver and kidney parenchyma due to wave reflection, liver parenchymal ultrasound attenuation, and blurred imaging of liver vessels and diaphragm, indicating fatty liver.

Exclusion Criteria:

• Female patients who are pregnant or breastfeeding.
• Diabetic patients undergoing medication treatment.
• Patients clinically diagnosed with alcoholic hepatitis, autoimmune hepatitis, or biliary liver disease.
• Excessive alcohol consumption (more than 15 grams/day for females, more than 30 grams/day for males).
• Users of weight-loss products and vitamin E supplements.
• Individuals with an estimated Glomerular Filtration Rate (eGFR) less than 60 mL/min/1.73m².

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo + metformin; Double blinded: matching placebo + metformin Placebo daily metformin 1500mg daily	Drug: Metformin; Tablets; Other Names: A10BA02; Drug: Placebo; Matching capsules
Experimental: Ganwei + metformin; Double blinded: Ganwei + metformin Ganwei 500mg/15 kg of body weight, daily metformin 1500mg daily	Drug: Metformin; Tablets; Other Names: A10BA02; Drug: Ganwei; Capsules; Other Names: HepatoKeeper
Placebo Comparator: Placebo; Double blinded: matching placebo Placebo daily	Drug: Placebo; Matching capsules
Experimental: Ganwei; Double blinded: Ganwei Ganwei 500mg/15 kg of body weight, daily	Drug: Ganwei; Capsules; Other Names: HepatoKeeper

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver steatosis severity: the change of CAP (dB/m) by Fibroscan	The effect of once daily, oral administration of 500 mg/15 kg of body weight Ganwei and/or 1500 mg metformin 24 weeks treatment versus before on the change in Controlled Attenuation Parameter(CAP) by FibroScan	Week 24
Liver fibrosis severity: the change of kPa by Fibroscan	The effect of once daily, oral administration of 500 mg/15 kg of body weight Ganwei and/or 1500 mg metformin 24 weeks treatment versus before on the change in kPa by FibroScan	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aspartate Transaminase (AST)	The effect of once daily, oral administration of 500 mg/15 kg of body weight Ganwei and/or 1500 mg metformin 24 weeks treatment versus before on the change in Aspartate Transaminase (AST)	Week 24
Alanine amino Transferase (ALT)	The effect of once daily, oral administration of 500 mg/15 kg of body weight Ganwei and/or 1500 mg metformin 24 weeks treatment versus before on the change in Alanine amino Transferase (ALT)	Week 24
Body mass index (BMI)	The effect of once daily, oral administration of 500 mg/15 kg of body weight Ganwei and/or 1500 mg metformin 24 weeks treatment versus before on the change in Body mass index (BMI)	Week 24
Glycated Hemoglobin (HbA1c)	The effect of once daily, oral administration of 500 mg/15 kg of body weight Ganwei and/or 1500 mg metformin 24 weeks treatment versus before on the change in Glycated Hemoglobin (HbA1c)	Week 24
White blood cell (WBC)	The effect of once daily, oral administration of 500 mg/15 kg of body weight Ganwei and/or 1500 mg metformin 24 weeks treatment versus before on the change in White blood cell (WBC)	Week 24
C-reactive protein (CRP)	The effect of once daily, oral administration of 500 mg/15 kg of body weight Ganwei and/or 1500 mg metformin 24 weeks treatment versus before on the change in C-reactive protein (CRP)	Week 24
Triglyceride (TG)	The effect of once daily, oral administration of 500 mg/15 kg of body weight Ganwei and/or 1500 mg metformin 24 weeks treatment versus before on the change in Triglyceride (TG)	Week 24
estimated Glomerular filtration rate (eGFR)	The effect of once daily, oral administration of 500 mg/15 kg of body weight Ganwei and/or 1500 mg metformin 24 weeks treatment versus before on the change in estimated Glomerular filtration rate (eGFR)	Week 24
Physical functioning	The effect of once daily, oral administration of 500 mg/15 kg of body weight Ganwei and/or 1500 mg metformin 24 weeks treatment versus before on the change in Physical functioning by 36-Item Short Form Health Survey (SF-36)	Week 24
Role limitations due to physical health	The effect of once daily, oral administration of 500 mg/15 kg of body weight Ganwei and/or 1500 mg metformin 24 weeks treatment versus before on the change in Role limitations due to physical health by 36-Item Short Form Health Survey (SF-36)	Week 24
Role limitations due to emotional problems	The effect of once daily, oral administration of 500 mg/15 kg of body weight Ganwei and/or 1500 mg metformin 24 weeks treatment versus before on the change in Role limitations due to emotional problems by 36-Item Short Form Health Survey (SF-36)	Week 24
Energy/fatigue	The effect of once daily, oral administration of 500 mg/15 kg of body weight Ganwei and/or 1500 mg metformin 24 weeks treatment versus before on the change in Energy/fatigue by 36-Item Short Form Health Survey (SF-36)	Week 24
Emotional well-being	The effect of once daily, oral administration of 500 mg/15 kg of body weight Ganwei and/or 1500 mg metformin 24 weeks treatment versus before on the change in Emotional well-being by 36-Item Short Form Health Survey (SF-36)	Week 24
Social functioning	The effect of once daily, oral administration of 500 mg/15 kg of body weight Ganwei and/or 1500 mg metformin 24 weeks treatment versus before on the change in Social functioning by 36-Item Short Form Health Survey (SF-36)	Week 24
Bodily pain	The effect of once daily, oral administration of 500 mg/15 kg of body weight Ganwei and/or 1500 mg metformin 24 weeks treatment versus before on the change in Pain by 36-Item Short Form Health Survey (SF-36)	Week 24
General health	The effect of once daily, oral administration of 500 mg/15 kg of body weight Ganwei and/or 1500 mg metformin 24 weeks treatment versus before on the change in General health by 36-Item Short Form Health Survey (SF-36)	Week 24

Collaborators and Investigators

• Sponsor: Taipei City Hospital
• Collaborators: The One Biopharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Chih-Lin Lin, MD., Department of Gastroenterology, Renai branch, Taipei City Hospital, Taipei, Taiwan.

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2021
• Primary Completion (Actual): March 14, 2023
• Study Completion (Actual): June 13, 2023

Study Registration Dates

• First Submitted: January 29, 2024
• First Submitted That Met QC Criteria: January 29, 2024
• First Posted (Actual): February 6, 2024

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Non-alcoholic fatty liver disease; metformin; Ganwei
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Fibrosis; Liver Diseases; Fatty Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: TCHIRB-11002006

Drug and device information, study documents

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