Metabolic Dysfunction-associated Fatty Liver Disease (MAFLD)
Conditions
Keywords
Non-alcoholic fatty liver, Traditional Chinese medicine, Non-alcoholic fatty liver disease, Metabolic dysfunction-associated fatty liver disease, Linzhi Jianghuang Fufang Huoxue Anshen Capsule
Brief summary
This is a randomized, double-blinded, placebo-controlled clinical trial aimed at evaluating the efficacy and safety of Linzhi Jianghuang Fufang Huoxue Anshen Capsule (LJF) for non-alcoholic fatty liver.
Detailed description
Non-alcoholic fatty liver disease (NAFLD), also known as metabolic dysfunction-associated fatty liver disease (MAFLD), refers to a spectrum of conditions characterized by abnormal lipid metabolism leading to fat accumulation within the liver. This spectrum includes non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), hepatic fibrosis, and cirrhosis. Linzhi Jianghuang Linzhi Jianghuang Fufang Huoxue Anshen Capsule (LJF) is composed of five herbs (e.g., Salviae Miltiorrhizae Radix et Rhizoma, Puerariae Lobatae Radix). A total of 180 participants aged 18-65 years with Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF) ≥ 10% will be recruited and randomized to receive either LJF or placebo in a 1:1 ratio for 24 weeks.
Interventions
DRUGLinzhi Jianghuang Fufang Huoxue Anshen Capsule (LJF)
Linzhi Jianghuang Fufang Huoxue Anshen Capsule (LJF) is composed of five herbs (e.g., Salviae Miltiorrhizae Radix et Rhizoma, Puerariae Lobatae Radix).
OTHERPlacebo
The placebo contains caramel color, sucrose octaacetate, sucralose, etc.
Sponsors
Hong Kong Baptist University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Participants, investigators, assessors, and statistician will be blinded to the group allocation.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 1\) Age between 18 and 65 years (inclusive); * 2\) Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF) ≥ 10%; * 3\) Liver stiffness measured by transient elastography \< 7.3 kPa; * 4\) Presence of one or more metabolic risk factors: a. Fasting plasma glucose ≥ 6.1 mmol/L, or 2-hour postprandial glucose ≥ 7.8 mmol/L, or HbA1c ≥ 5.7%, or a history of type 2 diabetes, or HOMA-IR ≥ 2.5; b. Arterial blood pressure ≥ 130/85 mmHg, or receiving antihypertensive medication; c. Fasting serum triglycerides ≥ 1.7 mmol/L; * 5\) Diagnosis of NAFLD with Phlegm-Stasis Obstructing Collateral pattern according to Traditional Chinese Medicine (TCM) criteria, formulated based on the "Consensus Opinion on Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment of Non-alcoholic Fatty Liver Disease (2017)": Primary Symptoms: a. Intercostal stabbing or dull pain; b. Palpable abdominal mass (hypochondriac mass); c. Dark or dull complexion; d. Obesity. Secondary Symptoms: a. Epigastric and chest fullness and oppression; b. Expectoration of sputum; c. Poor appetite and aversion to greasy food; d. Heavy sensation in the limbs. Tongue and Pulse: Dark red tongue with ecchymosis, enlarged tongue body with teeth marks, greasy coating; wiry, slippery, or hesitant pulse. Diagnosis can be established with the presence of at least 2 primary symptoms and 1 or 2 secondary symptoms, in conjunction with the tongue and pulse presentation. * 6\) Understand the trial content thoroughly and voluntarily sign the informed consent form.
Exclusion criteria
* 1\) Excessive alcohol intake (converted pure alcohol \> 210 g per week for men, \> 140 g per week for women), or an Alcohol Use Disorder Identification Test (AUDIT) score ≥ 8; * 2\) Other liver diseases (e.g., alcoholic hepatitis, viral hepatitis, drug-induced liver disease, Wilson's disease, autoimmune liver disease, etc.), or a history of liver transplantation or liver resection; * 3\) Presence of severe concurrent diseases affecting the heart, brain, hematopoietic system, immune system, or kidneys (BUN \> 1.5 × ULN, Cr \> ULN); * 4\) Presence of other endocrine system disorders, such as hyperthyroidism, Cushing's syndrome, etc.; * 5\) History of malignancy that has not been in complete remission for more than 5 years; * 6\) Hepatic decompensation (total bilirubin, platelet count, prothrombin time, albumin \> ULN; ALT or AST \> 2 × ULN), presence of ascites, varices, or a history of hepatic encephalopathy; * 7\) Poorly controlled severe hypertension, defined as systolic blood pressure ≥ 180 mmHg and/or diastolic blood pressure ≥ 110 mmHg; * 8\) Insulin-dependent diabetes mellitus (e.g., type 1 diabetes mellitus, or current use of insulin), or non-insulin-dependent diabetes mellitus with poor glycemic control (HbA1c ≥ 9.5%), or diabetic acute complications, or diabetes with severe chronic complications; * 9\) Use of medications that may cause hepatic steatosis or steatohepatitis (e.g., tamoxifen, amiodarone, glucocorticoids, tetracyclines, methotrexate, valproate, salicylates, estrogens) or potentially hepatotoxic drugs for 2 consecutive weeks or more within the past year; * 10\) Current use or use within the past 3 months of GLP-1 receptor agonists; * 11\) Adjustment of hypoglycemic, antihypertensive, or lipid-lowering medications within the past 3 months (e.g., adding or discontinuing medication, dose change, or irregular use); * 12\) Regular use of hepatoprotective drugs or vitamin E within the past month; * 13\) History of bariatric surgery within the past year, or body weight change \> 5% within the past 3 months; * 14\) History of surgery within the past month; * 15\) Coagulation abnormalities, or current use of medications or foods with anticoagulant effects (e.g., aspirin, warfarin, Panax notoginseng, safflower, Angelica sinensis, peach kernel, etc.); * 16\) Concomitant psychiatric or psychological disorders, or substance/drug abuse; * 17\) Known allergic constitution, or known allergy to any component of LJF; * 18\) Participation in another clinical trial within the past month; * 19\) Contraindications for MRI examination, such as claustrophobia or presence of metallic implants; * 20\) Individuals of childbearing potential (male or female) with fertility plans; pregnant or lactating women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MRI-PDFF | Week-0, week-24. | Primary endpoint will be the change in liver fat content from baseline, as measured by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF) after 24 weeks of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Liver fat content | Week-0, week-12, and week-24. | Changes in liver fat content from baseline, as measured by Liverscan. |
| Liver stiffness | Week-0, week-12, and week-24. | Changes in liver stiffness from baseline, as measured by Liverscan. |
| Metabolic parameter | Week-0, week-24. | Changes in metabolic parameter (e.g., insulin resistance) from baseline to the end of 24 weeks of treatment. |
| Anthropometric parameter | Week-0, week-12, and week-24. | Changes in anthropometric parameter (e.g., Body Mass Index) from baseline. |
| Fatty Liver Index | Week-0, week-24. | Change in Fatty Liver Index (FLI) score from baseline to the end of 24 weeks of treatment. It ranges from 0 to 100. A FLI \< 30 can be used to rule out and a FLI ≥ 60 to rule in hepatic steatosis. |
| Hepatic Steatosis Index | Week-0, week-24. | Change in Hepatic Steatosis Index (HSI) score from baseline to the end of 24 weeks of treatment. The result is expressed on a scale from 0 to 100, with values \<30 ruling out fatty liver, whereas values \>36 confirm its presence. |
| Fibrosis-4 Index | Week-0, week-24. | Change in Fibrosis-4 Index (FIB-4) score from baseline to the end of 24 weeks of treatment. A FIB-4 score below 1.30 generally indicates a low likelihood of liver fibrosis. |
| CLDQ-NAFLD | Week-0, week-12, and week-24. | Changes in the Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease (CLDQ-NAFLD) score. Each item is scored on a 7-point Likert scale, and the total score is the average of the 6 domain scores, with higher scores indicating better quality of life. |
| Sleep quality | Week-0, week-12, and week-24. | Sleep quality will be assessed using the Pittsburgh Sleep Quality Index (PSQI), a 19-item instrument whose items generate 7 component scores that are summed into a global score ranging from 0 to 21, with higher scores indicating poorer sleep quality. |
| Fatigue | Week-0, week-12, and week-24. | Fatigue will be assessed using the Chalder Fatigue Questionnaire (CFQ-11), an 11-item instrument whose scores are summed into a total score ranging from 0 to 33, with higher scores indicating greater fatigue. |
| Adverse events | From week-0 to week-24 | Adverse events (AEs) occurring from the participant's enrollment to the end of the trial and any abnormal changes in laboratory parameters will be recorded. |
Contacts
CONTACTJialing ZHANG, PhD
Outcome results
None listed