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Nonalcoholic Fatty LiverPhase 2NCT05084404

Efficacy and Safety of Guanabenz for Nonalcoholic Fatty Liver Disease

A Phase 2 study testing Experimental: 4 mg/day of WY-8678 (guanabenz acetate) and Experimental: 8 mg/day of WY-8678 (guanabenz acetate) in people with Nonalcoholic Fatty Liver and Nonalcoholic Steatohepatitis, run by Yokohama City University at 1 site in Japan.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

To investigate the efficacy and safety of 4 mg/day of WY-8678 (guanabenz acetate) and 8 mg/day of WY-8678 (guanabenz acetate) in patients with non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH patients) with hypertension Read more about this study

Who is it for?
Ages 20 to 75 years
What is being tested?
Experimental: 4 mg/day of WY-8678 (guanabenz acetate) and Experimental: 8 mg/day of WY-8678 (guanabenz acetate)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
1 siteJapan
Study dates
29 Oct 2021to 30 Jun 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients who have received a full explanation about this study and who have provided written consent.
  • Patients ≥ 20 years of age ≤ 75 years of age at the time consent was provided.
  • 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)
  • 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)
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  • Patients with magnetic resonance imaging (MRI)-proton density fat fraction (PDFF) liver fat mass ≥ 8% at screening.
  • Patients with magnetic resonance elastography (MRE) value ≤ 3.6 kPa at screening.
  • Patients with a body mass index (BMI) ≥ 25 kg/m2 at the time of screening.
  • Patients receiving diet or exercise therapy 12 weeks before screening, with no improvement.
  • Patients who are willing to maintain a stable diet and physical activity during the clinical trial.

Who cannot join

  • Pregnant, lactating, potentially pregnant women, or patients who do not agree to contraception during the trial period.
  • 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:
  • 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:
  • 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.
  • Patients with autoimmune hepatitis.
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  • Patients with primary biliary cholangitis, primary sclerosing cholangitis, Wilson's disease, α1-antitrypsin deficiency, hemochromatosis or iron overload, drug-induced or alcoholic liver disease, or a history of known biliary atresia.
  • 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:
  • Patients who used insulin, glucagon-like peptide-1 (GLP-1) receptor agonists, SGLT2 inhibitors, or thiazolidine 12 weeks before screening,
  • Patients who used ursodeoxycholic acid or vitamin E 12 weeks before screening,
  • Patients whose doses of dyslipidemia drugs or antihypertensive drugs were changed 12 weeks before screening,
  • Patients whose dose of oral diabetes treatment drug (dipeptidyl peptidase 4 [DPP-4] inhibitor, sulfonylurea [SU] preparation, α-glucosidase inhibitor, metformin) was changed 12 weeks before screening,
  • 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,
  • 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.

Trial locations and contacts

1 site in 1 country.

Japan1 site

  • Yokohama City University

    Yokohama, Kanagawa, 236-0004

Other trials in Japan

About this study

Official title: Phase II Physician-initiated Clinical Trial Investigating the Efficacy and Safety of Guanabenz Acetate for Non-alcoholic Fatty Liver Disease Associated With Hypertension

To investigate the efficacy and safety of 4 mg/day of WY-8678 (guanabenz acetate) and 8 mg/day of WY-8678 (guanabenz acetate) in patients with non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH patients) with hypertension

Being tested
Experimental: 4 mg/day of WY-8678 (guanabenz acetate), Experimental: 8 mg/day of WY-8678 (guanabenz acetate)
Keywords
Nonalcoholic Fatty Liver, Nonalcoholic Steatohepatitis, Guanabenz, Phase 2 trial
Medical subject headings
Non-alcoholic Fatty Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Experimental: 4 mg/day of WY-8678 (guanabenz acetate)Drug

    Patients with nonalcoholic fatty liver disease are administered 4 mg/day of WY-8678 (guanabenz acetate) twice daily for 16 weeks

  • Experimental: 8 mg/day of WY-8678 (guanabenz acetate)Drug

    Patients with nonalcoholic fatty liver disease are administered 8 mg/day of WY-8678 (guanabenz acetate) twice daily for 16 weeks

Study groups in NCT05084404
Study groupRoleWhat they receive
4 mg/day of WY-8678 (guanabenz acetate)ExperimentalNot described
Receives: Drug: Experimental: 4 mg/day of WY-8678 (guanabenz acetate)
8 mg/day of WY-8678 (guanabenz acetate)ExperimentalNot described
Receives: Drug: Experimental: 8 mg/day of WY-8678 (guanabenz acetate)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of those where the liver fat content (%) measured by MRI-PDFF at 16 weeks decreased by ≥ 3.46% from baseline (%)

    MRI-PDFF

    Measured: Week 16

Secondary outcomes (12)

  1. Percentage of those where the liver fat content (%) measured by MRI-PDFF at 16 weeks decreased by 3.46% or more from baseline for 4 mg group and 8 mg group (%)

    MRI-PDFF

    Measured: Week 16

  2. The absolute change in liver fat content measured by MRI-PDFF

    MRI-PDFF

    Measured: Week 16

  3. Rate of change in ALT

    Serum

    Measured: Week 16

  4. Rate of change in AST

    Serum

    Measured: Week 16

  5. Rate of change in gamma-glutamyl transferase (γ-GTP)

    Serum

    Measured: Week 16

  6. Rate of change in weight

    Body weight

    Measured: Week 16

  7. Rate of change in blood lipids

    Serum. Blood lipids defined as (chylomicron cholesterol, chylomicron triglyceride, lipoprotein cholesterol, low-density lipoprotein [LDL] triglyceride, very low-density lipoprotein [VLDL] cholesterol, VLDL triglyceride, free cholesterol, apoprotein A1, apoprotein B, adipsin, free fatty acid).

    Measured: Week 16

  8. Rate of change in insulin resistance (HOMA-IR)

    Blood

    Measured: Week 16

  9. Rate of change in liver stiffness

    MR elastography

    Measured: Week 16

  10. Rate of change in fibrosis markers (enhanced liver fibrosis [ELF] score)

    Serum

    Measured: Week 16

  11. Rate of change in fibrosis markers (enhanced liver fibrosis Fibrosis-4 [FIB-4])

    Serum

    Measured: Week 16

  12. Occurrence rate of adverse events

    Safety

    Measured: Week 0-16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Oct 2021
  2. Study start29 Oct 2021
  3. Primary completion28 Feb 2023 (estimated)
  4. Study completion30 Jun 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05084404
Sponsor's protocol ID
YCU-21001
Status last verified
Sep 2022
First submitted
24 Sep 2021
Last updated
27 Sep 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Iwaki M, Kessoku T, Tanaka K, Ozaki A, Kasai Y, Yamamoto A, Takahashi K, Kobayashi T, Nogami A, Honda Y, Ogawa Y, Imajo K, Yoneda M, Kobayashi N, Saito S, Nakajima A. Efficacy and safety of guanabenz acetate treatment for non-alcoholic fatty liver disease: a study protocol for a randomised investigator-initiated phase IIa study. BMJ Open. 2022 Jul 12;12(7):e060335. doi: 10.1136/bmjopen-2021-060335.

    PubMed 35820743

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Experimental: 4 mg/day of WY-8678 (guanabenz acetate) and Experimental: 8 mg/day of WY-8678 (guanabenz acetate) in people with Nonalcoholic Fatty Liver and Nonalcoholic Steatohepatitis, run by Yokohama City University at 1 site in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 27 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of those where the liver fat content (%) measured by MRI-PDFF at 16 weeks decreased by ≥ 3.46% from baseline (%) (time frame: Week 16). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05084404, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2022.

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