Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT06244550 |
| Other study ID # |
TCHIRB-11002006 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
September 22, 2021 |
| Est. completion date |
June 13, 2023 |
Study information
| Verified date |
January 2024 |
| Source |
Taipei City Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
