Clinical trial NCT06244550: Clinical Trials Using HepatoKeeper Herbal Essentials to Treat Non-alcoholic Fatty Liver Disease and Metabolic Factors
Official title: A Clinical Trial Using Ganwei (HepatoKeeper) Herbal Essentials to Treat Non-Alcoholic Fatty Liver Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non-alcoholic Fatty Liver Disease
Liver Fibrosis
Liver Injury
Keywords: Ganwei
Non-alcoholic fatty liver disease
metformin
Lead sponsor: Taipei City Hospital
Sponsor class: OTHER_GOV
Collaborators: name: The One Biopharmaceutical Co., Ltd.
First posted: 2024-02-06
Enrollment: 60
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Liver steatosis severity: the change of CAP (dB/m) by Fibroscan
timeFrame: Week 24
measure: Liver fibrosis severity: the change of kPa by Fibroscan
timeFrame: Week 24
Secondary outcomes:
measure: Aspartate Transaminase (AST)
timeFrame: Week 24
measure: Alanine amino Transferase (ALT)
timeFrame: Week 24
measure: Body mass index (BMI)
timeFrame: Week 24
measure: Glycated Hemoglobin (HbA1c)
timeFrame: Week 24
measure: White blood cell (WBC)
timeFrame: Week 24
measure: C-reactive protein (CRP)
timeFrame: Week 24
measure: Triglyceride (TG)
timeFrame: Week 24
measure: estimated Glomerular filtration rate (eGFR)
timeFrame: Week 24
measure: Physical functioning
timeFrame: Week 24
measure: Role limitations due to physical health
timeFrame: Week 24
measure: Role limitations due to emotional problems
timeFrame: Week 24
measure: Energy/fatigue
timeFrame: Week 24
measure: Emotional well-being
timeFrame: Week 24
measure: Social functioning
timeFrame: Week 24
measure: Bodily pain
timeFrame: Week 24
measure: General health
timeFrame: Week 24
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Taipei City Hospital
Study officials:
affiliation: Department of Gastroenterology, Renai branch, Taipei City Hospital, Taipei, Taiwan.
name: Chih-Lin Lin, MD.
role: PRINCIPAL_INVESTIGATOR
References: