Non-Alcoholic Fatty Liver DiseasePhase 3NCT04142749
Oltipraz for Liver Fat Reduction in Patients With Non-alcoholic Fatty Liver Disease Except for Liver Cirrhosis
A Phase 3 study testing Oltipraz in people with Non-Alcoholic Fatty Liver Disease, run by PharmaKing at 21 sites in South Korea.
Trial summary
Oltipraz inhibits fatty acid synthesis through AMPK-S6K1 pathway and LXRg-SREBP-1c pathway in liver. Read more about this study
- Who is it for?
- Ages 19 to 75 years
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease
- What is being tested?
- Oltipraz
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 146 participants
- Where
- 21 sitesSouth Korea
- Study dates
- 15 Nov 2019to 26 Sep 2022
- Phase
- Phase 3
- 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 19 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- Abdominal ultrasonography of Screening indicates that the liver is brighter than the spleen or kidneys, causing suspected fatty liver
- Persons with liver fat content is 20% or more on the MRS
- 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)
- Those who with an alcohol use disorder identification test (AUDIT) result point is no more than 7, during screening.
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- Persons with body mass index (BMI) more than 23 kg/m2 during screening
- A person who satisfies the following laboratory test results when screening
- Platelet ≥ 130,000/㎣
- White blood cell (WBC) ≥ 3,000/㎣
- Absolute neutrophil count (ANC) ≥ 1,500/㎣
- Albumin ≥ 3.5 g/dL
- Serum creatinine ≤ 1.5 X upper limit of normal (ULN)
- 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
Who cannot join
- A person who has history of following disease or surgery
- Malignant tumour with liver cancer
- Malignant tumor excluding liver cancer, However, registration is possible in the following cases
- If the investigator determines that the patient has been completely cured after maintaining the condition for at least five years
- 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.
- autoimmune disease (e.g., inflammatory bowel disease, autoimmune hemolytic disease, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, rheumatoid arthritis, severe psoriasis, etc.)
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- Bariatric surgery within 24 weeks before screening
- A Person who has comorbidity of the following diseases at the time of screening
- Liver cirrhosis identified by an epidemiological or histological examination
- 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
- A Person who has been infected or has Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV).
- Type 1 diabetes or type 2 diabetes (hemoglobin A1c (HbA1c) > 9%)
- A person who has positive result of Human immunodeficiency virus antibody (HIV Ab).
- 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
- 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
- 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
- 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
- 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.
- 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
Trial locations and contacts
21 sites in 1 country.
21 sites in 1 country
South Korea21 sites
Catholic University Bucheon ST. Mary's Hospital
Bucheon-si
Soonchunhyang University Bucheon Hospital
Bucheon-si
Dong-A University Hospital
Busan, 49201
Keimyung University Dongsan Medical Center
Daegu
Gangneung Asan Medical Center
Gangneung-si
Inje University Ilsan Paik Hospital
Goyang-si, Gyeonggi-do, 411-706
NHUS Ilsan Hospital
Goyang-si, 410-719
Inha University Hospital
Incheon, Junggu
Seoul National University Hospital
Seoul, 110-744
Boramae Hospital
Seoul, 156-707
Chung-Ang University Hosptial
Seoul
Hallym University Gangnam Sungsim Hospital
Seoul
Hanyang University Hospital
Seoul
Korea University Guro Hospital
Seoul
National Medical Center
Seoul
Severance Hospital
Seoul
Soonchunhyang University Seoul Hospital
Seoul
Yonsei University Gangnam Severance Hospital
Seoul
Ajou University School of Medicine
Suwon
The Catholic University of Korea, Uijeongbu ST. Mary's Hospital
Uijeongbu-si, Gyeonggi-do
Wonju Severance Christian Hospital
Wanju
About this study
Official title: A Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Oltipraz
Oltipraz inhibits fatty acid synthesis through AMPK-S6K1 pathway and LXRg-SREBP-1c pathway in liver.
Read the detailed description
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
- Non-Alcoholic Fatty Liver Disease
- Being tested
- Oltipraz, Placebos
- 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.
OltiprazDrug
Total 90mg, By mouth, TID
PlacebosDrug
Also called Placebo
Total 90mg, By mouth, TID
| Study group | Role | What they receive |
|---|---|---|
| Oltipraz | Active comparator | Oltipraz 30mg Receives: Drug: Oltipraz |
| Placebo | Placebo comparator | Placebo 30mg Receives: Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
Variation of liver fat assessed
Variation of liver fat assessed by MRS at 24 weeks compared to the baseline (%)
Measured: 24 weeks compared to the baseline
Secondary outcomes (10)
The variation in the amount of liver fat
The variation in the amount of liver fat assessed by the MRS at the time of 24 weeks compared to the baseline
Measured: 24 weeks compared to the baseline
Variation of liver fat certificate grade
Variation of liver fat certificate grade assessed by ultrasonic waves
Measured: 24 weeks compared to the baseline
Variation of NFS variation
Variation of NFS at 24 weeks compared to the baseline
Measured: 24 weeks compared to the baseline
Variation of liver elasticities and fatty acids
Variation of liver elasticities and fatty acids assessed by fibroscan at 24 weeks time compared to baseline
Measured: 24 weeks compared to the baseline
FIB-4
Variation of FIB-4 from 8 weeks, 16 weeks and 24 weeks to baseline
Measured: 8 weeks, 16 weeks and 24 weeks
BMI
BMI variation at 8 weeks, 16 weeks and 24 weeks relative to the baseline
Measured: 8 weeks, 16 weeks and 24 weeks
Variation of ALT, AST, γ-glutamyl transferase (GGT)
Variation of ALT, AST, γ-glutamyl transferase (GGT) in time of 8 weeks, 16 weeks and 24 weeks relative to the baseline
Measured: 8 weeks, 16 weeks and 24 weeks
Cholesterol (total, low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), triglyceride (TG)
Variation of Cholesterol (total, low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), triglyceride (TG)
Measured: 8 weeks, 16 weeks and 24 weeks
Variation of Homeostatic model adjustment-insulin resistance (HOMA-IR) index
Variation of Homeostatic model adjustment-insulin resistance (HOMA-IR = fasting insulin (μU/mL) × fasting glucose (mmol/L) / 22.5)
Measured: 24 weeks compared to the baseline
Waist circumference
The variation of waist circumference compared to the baseline at 24 weeks
Measured: 24 weeks compared to the baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2019
- Study start15 Nov 2019
- Primary completion2 Sep 2022
- Study completion26 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 146 participants (actual)
Sponsor and investigators
- Lead sponsor
- PharmaKing
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yun-Jun Kim, MD.PhD, Principal investigator, Seoul Nat'l Uni. HospitalChanguk Kim, MD.PhD, Principal investigator, The Catholic University of Korea, Uijeongbu St. Mary's HospitalGapjin Chun, MD.PhD, Principal investigator, Gangneung Asan Medical CenterTaehui Lee, MD.PhD, Principal investigator, Kunyang University HospitalByeongguk Jang, MD.PhD, Principal investigator, Keimyung University Dongsan Medical CenterYanghyeon Baek, MD.PhD, Principal investigator, Dong-A University HospitalByeonggwan Kim, MD.PhD, Principal investigator, Boramae HospitalYeongseok Kim, MD.PhD, Principal investigator, Soonchunhyang University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04142749
- Sponsor's protocol ID
- PMK-N01GI1-P3
- Status last verified
- Oct 2022
- First submitted
- 19 Sep 2019
- Last updated
- 6 Oct 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Oltipraz
- ClinicalTrials.gov ID
- NCT04142749
- Acronym / sponsor ID
- PMK-N01GI1-P3
- Conditions
- Non-Alcoholic Fatty Liver Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 146 participants (actual)
- Lead sponsor
- PharmaKingIndustry (pharma, biotech, devices)
- Study start
- 15 Nov 2019 (actual)
- Primary completion
- 2 Sep 2022 (actual)
- Study completion
- 26 Sep 2022 (actual)
- First posted
- 29 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Oltipraz inhibits fatty acid synthesis through AMPK-S6K1 pathway and LXRg-SREBP-1c pathway in liver.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oltipraz | Active comparator | Drug: OltiprazOltipraz 30mg |
| Placebo | Placebo comparator | Drug: PlacebosPlacebo 30mg |
Who may qualify
- Ages
- 19 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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:
- Persons with body mass index (BMI) more than 23 kg/m2 during screening
- A person who satisfies the following laboratory test results when screening
- 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.
Key exclusion criteria (28 listed)
- A person who has history of following disease or surgery
- A Person who has comorbidity of the following diseases at the time of screening
- A person with AST/ALT ratio of more than 2 at screening
- The person who has the following medication history
- A person who receive non-drug treatment that may affect the liver within 4 weeks prior to screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OltiprazTotal 90mg, By mouth, TID | Drug | Oltipraz |
| PlacebosAlso: PlaceboTotal 90mg, By mouth, TID | Drug | Placebo |
Primary outcome
Variation of liver fat assessed
Time frame: 24 weeks compared to the baseline
Variation of liver fat assessed by MRS at 24 weeks compared to the baseline (%)
10 secondary outcomes
The variation in the amount of liver fat
Time frame: 24 weeks compared to the baseline
Variation of liver fat certificate grade
Time frame: 24 weeks compared to the baseline
Variation of NFS variation
Time frame: 24 weeks compared to the baseline
Variation of liver elasticities and fatty acids
Time frame: 24 weeks compared to the baseline
FIB-4
Time frame: 8 weeks, 16 weeks and 24 weeks
BMI
Time frame: 8 weeks, 16 weeks and 24 weeks
Variation of ALT, AST, γ-glutamyl transferase (GGT)
Time frame: 8 weeks, 16 weeks and 24 weeks
Cholesterol (total, low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), triglyceride (TG)
Time frame: 8 weeks, 16 weeks and 24 weeks
Variation of Homeostatic model adjustment-insulin resistance (HOMA-IR) index
Time frame: 24 weeks compared to the baseline
Waist circumference
Time frame: 24 weeks compared to the baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yun-Jun Kim, MD.PhD principal investigator
Seoul Nat'l Uni. Hospital
Changuk Kim, MD.PhD principal investigator
The Catholic University of Korea, Uijeongbu St. Mary's Hospital
Gapjin Chun, MD.PhD principal investigator
Gangneung Asan Medical Center
21 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Oltipraz in people with Non-Alcoholic Fatty Liver Disease, run by PharmaKing at 21 sites in South Korea.
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 16 inclusion and 28 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: finished, as of the sponsor's last update on 6 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in South Korea. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Variation of liver fat assessed (time frame: 24 weeks compared to the baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Oct 2022.