Oltipraz for Liver Fat Reduction in Patients With Non-alcoholic Fatty Liver Disease Except for Liver Cirrhosis

NCT ID: NCT04142749

Last Updated: 2022-10-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

146 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-11-15

Study Completion Date

2022-09-26

Brief Summary

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Oltipraz inhibits fatty acid synthesis through AMPK-S6K1 pathway and LXRg-SREBP-1c pathway in liver.

Detailed Description

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Dithiolethiones, a novel class of adenosine monophosphate-activated protein kinase (AMPK) activators, prevent insulin resistance through AMPK-dependent p70 ribosomal S6 kinase-1 (S6K1) inhibition. And it is well known that the modulation of S6K1 by oltipraz inhibited the development of insulin resistance and hyperglycemia through the AMPK-S6K1 pathway.Also some research reported that LXRg (a member of the nuclear hormone receptor)-mediated increases in SREBP-1c (the sterol regulatory element-binding protein-1c gene) promote the expression of lipogenic genes and enhance fatty acid synthesis and oltipraz inhibits LXRg and SREBP-c. Therefore, Oltipraz inhibits fatty acid synthesis through AMPK-S6K1 pathway and LXRg-SREBP-1c pathway in liver.

Conditions

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Non-Alcoholic Fatty Liver Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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Oltipraz

Oltipraz 30mg

Group Type ACTIVE_COMPARATOR

Oltipraz

Intervention Type DRUG

Total 90mg, By mouth, TID

Placebo

Placebo 30mg

Group Type PLACEBO_COMPARATOR

Placebos

Intervention Type DRUG

Total 90mg, By mouth, TID

Interventions

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Oltipraz

Total 90mg, By mouth, TID

Intervention Type DRUG

Placebos

Total 90mg, By mouth, TID

Intervention Type DRUG

Other Intervention Names

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Placebo

Eligibility Criteria

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Inclusion Criteria

* A person the ages of 19 and 75 years old
* Patients with non-alcoholic fatty liver disease other than cirrhosis that meets all of the following criteria:

1. Abdominal ultrasonography of Screening indicates that the liver is brighter than the spleen or kidneys, causing suspected fatty liver
2. Persons with liver fat content is 20% or more on the MRS
3. Those who do not have significant alcohol intake within two years before screening (men: no more than 210 g per week; women: no more than 140 g per week)
4. Those who with an alcohol use disorder identification test (AUDIT) result point is no more than 7, during screening.
* Persons with body mass index (BMI) more than 23 kg/m2 during screening
* A person who satisfies the following laboratory test results when screening

1. Platelet ≥ 130,000/㎣
2. White blood cell (WBC) ≥ 3,000/㎣
3. Absolute neutrophil count (ANC) ≥ 1,500/㎣
4. Albumin ≥ 3.5 g/dL
5. Serum creatinine ≤ 1.5 X upper limit of normal (ULN)
6. ULN \< Alanine transaminase (ALT) or aspartate transaminase (AST) ≤ 250 IU/L
* A person who is willing to maintain the same lifestyle (exercise, alcohol intake, diet, etc.) maintained for at least four weeks before screening during the clinical trial period.
* A person who voluntarily agrees to participate in this clinical trial

Exclusion Criteria

* A person who has history of following disease or surgery

1. Malignant tumour with liver cancer
2. Malignant tumor excluding liver cancer, However, registration is possible in the following cases

1. If the investigator determines that the patient has been completely cured after maintaining the condition for at least five years
2. In case of basal cell or squamous cell carcinoma of the skin, the patient is able to maintain a complete condition for more than three years in the case of cainoma in the cervix (CIN) and carcinema in situ (CIS), and other areas.
3. autoimmune disease (e.g., inflammatory bowel disease, autoimmune hemolytic disease, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, rheumatoid arthritis, severe psoriasis, etc.)
4. Bariatric surgery within 24 weeks before screening
* A Person who has comorbidity of the following diseases at the time of screening

1. Liver cirrhosis identified by an epidemiological or histological examination
2. Cumulative disease (e.g., alcohol liver disease, toxic hepatitis, autoimmune liver disease, metabolic liver disease, biliary closure, etc.) that may indicates liver abnormalities other than non-alcoholic fatty liver disease
3. A Person who has been infected or has Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV).
4. Type 1 diabetes or type 2 diabetes (hemoglobin A1c (HbA1c) \> 9%)
5. A person who has positive result of Human immunodeficiency virus antibody (HIV Ab).
6. A persons with conditions that may affect the effectiveness and safety by investigator
* A person with AST/ALT ratio of more than 2 at screening
* The person who has the following medication history

1. Persons administered vitamin E (≥ 800 IU/day) or thiazolidatedione drugs or glucagon-like peptide-1 (GLP-1) agonist drugs within 12 weeks prior to screening
2. Persons who were given antiobestic drug within 12 weeks of screening For example; antiobestic drug with Central nervous system action: Amfepramone, bupropion and naltrexone, cathine, clobenzorex, dexfenfluramine, ephedrine combinations, etilamfetamine, fenfluramine, lorcaserin, mazindol, mefenorex, phentermine, sibutramine, Peripheral neurotic Obesity drugs: Orlistat, Rimonabant, etc
3. A person who received medications that could cause fatty liver disease within 8 weeks prior to screening For example; Administration of systemic glucocorticoids for more than two weeks Anabolic steroid-based drug, Estrogen-based drug, Azole-based antimicrobial agent, Nucleoside, Nucleotide reverse transcriptase inhibitor-based drug, Tetracycline-based drug, Amiodarone, tamoxifen, methotrexate, valproic acid, etc
4. A person who administered drugs that may affect the progress of non-alcoholic fatty liver disease within 4 weeks prior to screening or who require administration during clinical trials For example; Silymarin, biphenyl dimethyl dicarboxylate (DDB), ursodeoxycholic acid (UDCA), S-adenosyl-L-methionine (SAMe), betaine, pentoxyfylline, sodium-glucose cotransporter-2 (SGLT-2) inhibitor, omega 3 fatty acid, etc.

1. However, the following drugs can be registered if they are under stable dosage for at least 12 weeks and are expected to remain unchanged during clinical trials; Sulfonylurea-based drug, metformin, insulin, dipeptidyl peptidase-4 inhibitor (DPP-4 inhibitor), a-glucosidase inhibitor (a-GI), meglitinide-based drug, statin-based drug, fibrate-based drug, nicotinic acid, ezetimibe, beta-blockers based drug, thiazide based drug
* A person who receive non-drug treatment that may affect the liver within 4 weeks prior to screening.
* A person who administered/treated with other clinical trials/medical devices within 4 weeks prior to screening
* Those who are not able to MRS(I)
* A female who is pregnant, may be pregnant, or is lactating
* A person who is not willing to use appropriate contraceptives during this clinical trial.
* A person who is hypersensitive to the Investigational Product
* A person who is deemed ineligible for clinical trials by the investigator
Minimum Eligible Age

19 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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PharmaKing

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Yun-Jun Kim, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

Seoul Nat'l Uni. Hospital

Changuk Kim, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

The Catholic University of Korea, Uijeongbu ST. Mary's Hospital

Gapjin Chun, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

Gangneung Asan Medical Center

Taehui Lee, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

Kunyang University Hospital

Byeongguk Jang, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

Keimyung University Dongsan Medical Center

Yanghyeon Baek, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

Dong-A University Hospital

Byeonggwan Kim, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

Boramae Hospital

Yeongseok Kim, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

Soonchunhyang University Hospital

Jaeyeong Chang, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

Soonchunhyang University Hospital

Jaeyeong Jung, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

Ajou University School of Medicine

Hyeonung Lee, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

Yonsei University Gangnam Severance Hospital

Doyeong Kim, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

Severance Hospital

Munyeong Kim, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

Wonju Severance Christian Hospital

Junseong Lee, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

Inje University Ilsan Baek Hospital

Jinu Lee, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

Inha University Hospital

Hyeongjun Kim, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

Chung-Ang University Hosptial, Chung-Ang University College of Medicine

Sanghun Park, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

Hallym University Gangnam Sungsim Hospital

Daewon Jun, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

Hanyang University

Chun Kyun Lee, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

National Health Insurance Service Ilsan Hospital

Jaeyun Jung, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

National medical center

Jihun Kim, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

Korea University Guro Hospital

Huieon Kim, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

Catholic University Bucheon ST. Mary's Hospital

Locations

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Inje University Ilsan Paik Hospital

Goyang-si, Gyeonggi-do, South Korea

Site Status

The Catholic University of Korea, Uijeongbu ST. Mary's Hospital

Uijeongbu-si, Gyeonggi-do, South Korea

Site Status

Inha University Hospital

Incheon, Junggu, South Korea

Site Status

Catholic University Bucheon ST. Mary's Hospital

Bucheon-si, , South Korea

Site Status

Soonchunhyang University Bucheon Hospital

Bucheon-si, , South Korea

Site Status

Dong-A University Hospital

Busan, , South Korea

Site Status

Keimyung University Dongsan Medical Center

Daegu, , South Korea

Site Status

Gangneung Asan Medical Center

Gangneung-si, , South Korea

Site Status

NHUS Ilsan Hospital

Goyang-si, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Boramae Hospital

Seoul, , South Korea

Site Status

Chung-Ang University Hosptial

Seoul, , South Korea

Site Status

Hallym University Gangnam Sungsim Hospital

Seoul, , South Korea

Site Status

Hanyang University Hospital

Seoul, , South Korea

Site Status

Korea University Guro Hospital

Seoul, , South Korea

Site Status

National Medical Center

Seoul, , South Korea

Site Status

Severance Hospital

Seoul, , South Korea

Site Status

Soonchunhyang University Seoul Hospital

Seoul, , South Korea

Site Status

Yonsei University Gangnam Severance Hospital

Seoul, , South Korea

Site Status

Ajou University School of Medicine

Suwon, , South Korea

Site Status

Wonju Severance Christian Hospital

Wanju, , South Korea

Site Status

Countries

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South Korea

Other Identifiers

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PMK-N01GI1-P3

Identifier Type: -

Identifier Source: org_study_id

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