| Eligibility |
Inclusion Criteria:
1. Patients who have received a full explanation about this study and who have provided
written consent.
2. Patients = 20 years of age = 75 years of age at the time consent was provided.
3. Patients diagnosed with essential hypertension and whose systolic blood pressure at
the time of screening is = 130 mmHg and/or diastolic blood pressure is = 85 mmHg
(according to the diagnostic criteria for metabolic syndrome)
4. Patients diagnosed with NAFLD/NASH who meet the following criteria (1) or (2) (1)
Patients diagnosed with NAFLD who meet the following three criteria: ·Diagnostic
imaging or histological evidence of fatty liver, ·Alcohol intake < 30 g/day for men
and < 20 g/day for women for 12 or more consecutive weeks one year before screening,
·Absence of other factors that cause fattening or chronic liver disease. (2) Patients
with a definitive diagnosis of NASH by biopsy within 32 weeks before screening * The
definitive diagnostic criteria for NASH are defined as a fibrosis stage in liver
biopsy in the evaluation using the "NASH Clinical Research Network (CRN) criteria" by
an F1-F3 pathologist and a NAFLD activity score (NAS) =4 points (each item has one or
more points): ·Steatosis (0-3 points)
- Ballooning (0-2 points)
- Inflammation in the lobules (0-3 points)
5. Patients with magnetic resonance imaging (MRI)-proton density fat fraction (PDFF)
liver fat mass = 8% at screening.
6. Patients with magnetic resonance elastography (MRE) value = 3.6 kPa at screening.
7. Patients with a body mass index (BMI) = 25 kg/m2 at the time of screening.
8. Patients receiving diet or exercise therapy 12 weeks before screening, with no
improvement.
9. Patients who are willing to maintain a stable diet and physical activity during the
clinical trial.
Exclusion Criteria:
1. Pregnant, lactating, potentially pregnant women, or patients who do not agree to
contraception during the trial period.
2. Patients who have taken guanabenz acetate within 16 weeks prior to screening or who
have participated in other clinical studies (observational studies are excluded).
3. Patients with drug allergies to guanabenz acetate. 4. Patients with liver failure or
cirrhosis. 5. Patients with the following laboratory test values:
(1) Alanine aminotransferase (ALT) > 430 IU/L (males) or > 240 IU/L (female); or aspartate
aminotransferase (AST) > 300 IU/L (males and females) (2) Prothrombin time-international
normalized ratio (PT-INR) = 1.5 (excluding anticoagulant therapy) (3) Total bilirubin value
> 2.0 mg/dL (excluding definitive diagnosis of Gilbert syndrome) (4) Platelet count <
80,000/µL (5) Estimated glomerular filtration ratio (eGFR) < 45 (calculated by body surface
area correction: standardized eGFR) 6. Patients with a history of acute or chronic liver
disease other than NAFLD/NASH and complications:
1. Patients suffering from hepatitis B (defined by hepatitis B surface (HBs) antigen
positive at the time of screening) or hepatitis C (defined by hepatitis C virus (HCV)
antibody positive at the time of screening). However, anti-HCV antibody positive
patients who are judged to be negative for hepatitis C virus ribonucleic acid
(HCV-RNA) can be registered if they can be confirmed to be negative for at least one
year before screening.
2. Patients with autoimmune hepatitis.
3. Patients with primary biliary cholangitis, primary sclerosing cholangitis, Wilson's
disease, a1-antitrypsin deficiency, hemochromatosis or iron overload, drug-induced or
alcoholic liver disease, or a history of known biliary atresia.
4. Patients with suspicion or definitive diagnosis of hepatocellular carcinoma. 7.
Patients with a history of human immunodeficiency virus (HIV) infection. 8. Patients
with findings of portal hypertension (complications: ascites, hepatic encephalopathy,
varicose veins, splenomegaly).
9. Patients with a history of NAFLD-related drugs (amiodarone, methotrexate, systemic
glucocorticoids, tetracycline, tamoxifen, higher doses of estrogen, anabolic steroids or
valproic acid than used for hormone replacement) or other hepatotoxins for at least 4 weeks
prior to screening.
10. Patients who have used the following drugs:
1. Patients who used insulin, glucagon-like peptide-1 (GLP-1) receptor agonists, SGLT2
inhibitors, or thiazolidine 12 weeks before screening,
2. Patients who used ursodeoxycholic acid or vitamin E 12 weeks before screening,
3. Patients whose doses of dyslipidemia drugs or antihypertensive drugs were changed 12
weeks before screening,
4. Patients whose dose of oral diabetes treatment drug (dipeptidyl peptidase 4 [DPP-4]
inhibitor, sulfonylurea [SU] preparation, a-glucosidase inhibitor, metformin) was
changed 12 weeks before screening,
5. Patients who used drugs known to have a significant effect on body weight (including
over-the-counter drugs for weight loss) 12 weeks before screening,
6. Patients using central nervous system depressants (barbital, sodium thiopental,
morphine hydrochloride hydrate, brotizolam, diazepam, etc.).
11. Patients with 10% weight change 24 weeks before screening. 12. Patients scheduled to
undergo surgery after obesity surgery (such as gastroplasty and Roux-en-Y gastric bypass
surgery) or during the trial period.
13. Patients with a history of type 1 diabetes. 14. Patients with hemoglobin A1c (HbA1c) >
9.5% at screening or with uncontrolled type 2 diabetes.
15. Patients with hyperthyroidism or hypothyroidism, or screening results showing thyroid
dysfunction. However, for hypothyroidism, registration is possible if thyroid replacement
therapy is received 12 weeks before screening and the test values are stable.
16. Patients with a history of New York heart association functional classification (NYHA
classification) class III or IV heart failure due to factors other than hypertension.
17. Patients with a history of myocardial infarction, unstable angina, percutaneous
coronary intervention, coronary artery bypass grafting, or stroke or major surgery 24 weeks
before screening.
18. Patients with a history of substance abuse. 19. Patients with malignant tumors.
However, patients who have undergone radical surgery, patients who have completed
chemotherapy/radiation therapy, and patients who are undergoing hormone therapy can be
registered.
20. Patients with known intolerance to MRI or patients who are contraindicated for MRI
examination.
21. Other patients who the principal investigator or sub-investigator deems inappropriate
for conducting this clinical trial.
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