Non-alcoholic Fatty Liver DiseasePhase 2PMK-N01GI1NCT01373554
Efficacy and Safety of Oltipraz in the Patients With Non-alcoholic Fatty Liver Disease
A Phase 2 study testing Oltipraz in people with Non-alcoholic Fatty Liver Disease, run by PharmaKing at 5 sites in South Korea.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Non-alcoholic Fatty Liver Disease
- What is being tested?
- Oltipraz
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 5 sitesSouth Korea
- Study dates
- May 2011to Oct 2013
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients over 18, under 75 years of age
- Patients with non-alcoholic fatty liver disease
Who cannot join
- Over 2 ratio of AST to ALT
- Type 1 diabetes mellitus (insulin-dependent diabetes mellitus)
- Disorder in liver function with an exception of non-alcoholic fatty liver (e.g. Virus infection, biliary atresia, autoimmune hepatitis and etc.)
- Patients who have been taken drugs induced fatty liver for over 3 month within 1 year of participation in this study; amiodarone, tamoxifen, methotrexate, tetracyclines, glucocorticoids, anabolic steroids, over usual dose of estrogen for hormone replacement therapy and valproate
- Patients who has been taken any medications that could affect the treatment for non-alcoholic steatohepatitis: insulin, insulin sensitizer(metformin, thiazolidinedione), high dose of vitamin E, high dose of UDCA, pentoxifylline, SAM-e, Betaine, types of Statin, types of fibrate and orlistat
- Patients who had a Bariatric surgery less than 6 month prior to the participation in the study
Show all 14Show fewer
- Patients who are judged by investigator that participation of the study is difficult due to disease as follow; hepatic cirrhosis, Wilson's disease, malignant tumor, serious metabolic disease, severe renal disease, severe pulmonary disease, severe cardiovascular disease, severe nervous disease/psychiatric disorder, muscle disease and etc
- Any history of immune disorder which affect the changes in cytokine:
- inflammatory bowel disease, autoimmune thrombocytopenic purpura, system lupus erythematosus, autoimmune hemolytic anemia, severe psoriasis, rheumatic arthritis and etc
- Patients who have received treatment that may affect liver function within 1 month prior to the participation in the study
- Patient who has been administered other investigational product within 1 month prior to the participation in the study
- Patient who is not allowed to get MRS test: pacemaker, shunt and etc
- Pregnant or nursing women
- Patient who considered ineligible for participation in the study as Investigator's judgment
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
South Korea5 sites
Seoul National University Hospital
Daehak-ro Jongno-gu, Seoul, 110-744
Inje University Ilsan Paik Hospital
Dahwa-dong, Ilsanseo-gu, Goyang-si, Gyeonggi-do, 411-706
Korea University Guro hospital
Gurodong-ro, Seoul, 152-703
NHUS Ilsan Hospital
Ilsan-ro Ilsan-donggu, Goyang-si, 410-719
Boramae Hospital
Sindaebang-dong Dongjak-gu, Seoul, 156-707
About this study
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled, A Multicenter, Randomized, Double-blind, Placebo-controlled, 3 Parallel Groups, Phase 2 Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Oltipraz in Patients With Non-alcoholic Fatty Liver Disease (Except Liver Cirrhosis)
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
- Placebo, Oltipraz
- 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.
PlaceboDrug
30mig/bid or 60mg/bid P.O
OltiprazDrug
30mig/bid or 60mg/bid P.O
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| Oltipraz | Experimental | Not described Receives: Drug: Oltipraz |
What is being measured
The primary outcome is the main question the study is designed to answer.
MRS
To evaluate the efficacy of the Oltipraz on change in quantity of liver fat concentration assessed by MRS from baseline to 24 weeks in patients with non-alcoholic fatty liver disease
Measured: 24 weeks
Secondary outcomes (5)
change in ALT, AST and total bilirubin
Measured: 24 weeks
change in Cholesterol, Triglyceride
Measured: 24 weeks
change in HOMA-IR
Measured: 24 weeks
change in BMI
Measured: 24 weeks
changes in NAS
Subjects with liver biopsy:
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2011 (estimated)
- Study startMay 2011
- Primary completionJun 2013
- Study completionOct 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- PharmaKing
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- YoonJun Kim, MD.PhD, Principal investigator, Seoul National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01373554
- Sponsor's protocol ID
- PMK-N01GI1
- Acronym
- PMK-N01GI1
- Status last verified
- Dec 2013
- First submitted
- 3 Jun 2011
- Last updated
- 10 Dec 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Kim SG, Kim YM, Choi YH, Lee MG, Choi JY, Han JY, Cho SH, Jang JW, Um SH, Chon CY, Lee DH, Jang JJ, Yu ES, Lee YS. Pharmacokinetics of oltipraz and its major metabolite (RM) in patients with liver fibrosis or cirrhosis: relationship with suppression of circulating TGF-beta1. Clin Pharmacol Ther. 2010 Sep;88(3):360-8. doi: 10.1038/clpt.2010.89. Epub 2010 Jul 21.
PubMed 20664537Kim W, Kim BG, Lee JS, Lee CK, Yeon JE, Chang MS, Kim JH, Kim H, Yi S, Lee J, Cho JY, Kim SG, Lee JH, Kim YJ. Randomised clinical trial: the efficacy and safety of oltipraz, a liver X receptor alpha-inhibitory dithiolethione in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2017 Apr;45(8):1073-1083. doi: 10.1111/apt.13981. Epub 2017 Feb 22.
PubMed 28225186
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-blind, Placebo-controlled, A Multicenter, Randomized, Double-blind, Placebo-controlled, 3 Parallel Groups, Phase 2 Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Oltipraz in Patients With Non-alcoholic Fatty Liver Disease (Except Liver Cirrhosis)
- ClinicalTrials.gov ID
- NCT01373554
- Acronym / sponsor ID
- PMK-N01GI1 / PMK-N01GI1
- Conditions
- Non-alcoholic Fatty Liver Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- PharmaKingIndustry (pharma, biotech, devices)
- Study start
- May 2011
- Primary completion
- Jun 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 15 Jun 2011 (estimated)
- 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.
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
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo |
| Oltipraz | Experimental | Drug: Oltipraz |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients over 18, under 75 years of age
- Patients with non-alcoholic fatty liver disease
Key exclusion criteria (14 listed)
- Over 2 ratio of AST to ALT
- Type 1 diabetes mellitus (insulin-dependent diabetes mellitus)
- Disorder in liver function with an exception of non-alcoholic fatty liver (e.g. Virus infection, biliary atresia, autoimmune hepatitis and etc.)
- Patients who have been taken drugs induced fatty liver for over 3 month within 1 year of participation in this study; amiodarone, tamoxifen, methotrexate, tetracyclines, glucocorticoids, anabolic steroids, over usual dose of estrogen for hormone replacement therapy and valproate
- Patients who has been taken any medications that could affect the treatment for non-alcoholic steatohepatitis: insulin, insulin sensitizer(metformin, thiazolidinedione), high dose of vitamin E, high dose of UDCA, pentoxifylline, SAM-e, Betaine, types of Statin, types of fibrate and orlistat
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 |
|---|---|---|
| Placebo30mig/bid or 60mg/bid P.O | Drug | Placebo |
| Oltipraz30mig/bid or 60mg/bid P.O | Drug | Oltipraz |
Primary outcome
MRS
Time frame: 24 weeks
To evaluate the efficacy of the Oltipraz on change in quantity of liver fat concentration assessed by MRS from baseline to 24 weeks in patients with non-alcoholic fatty liver disease
5 secondary outcomes
change in ALT, AST and total bilirubin
Time frame: 24 weeks
change in Cholesterol, Triglyceride
Time frame: 24 weeks
change in HOMA-IR
Time frame: 24 weeks
change in BMI
Time frame: 24 weeks
changes in NAS
Time frame: 24 weeks
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 10 Dec 2013.
- Background: PubMed 20664537Kim SG, Kim YM, Choi YH, Lee MG, Choi JY, Han JY, Cho SH, Jang JW, Um SH, Chon CY, Lee DH, Jang JJ, Yu ES, Lee YS. Pharmacokinetics of oltipraz and its major metabolite (RM) in patients with liver fibrosis or cirrhosis: relationship with suppression of circulating TGF-beta1. Clin Pharmacol Ther. 2010 Sep;88(3):360-8. doi: 10.1038/clpt.2010.89. Epub 2010 Jul 21.
- Derived from this study: PubMed 28225186Kim W, Kim BG, Lee JS, Lee CK, Yeon JE, Chang MS, Kim JH, Kim H, Yi S, Lee J, Cho JY, Kim SG, Lee JH, Kim YJ. Randomised clinical trial: the efficacy and safety of oltipraz, a liver X receptor alpha-inhibitory dithiolethione in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2017 Apr;45(8):1073-1083. doi: 10.1111/apt.13981. Epub 2017 Feb 22.
- OltiprazLink provided by the sponsor.
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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.
YoonJun Kim, MD.PhD principal investigator
Seoul National University Hospital
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Oltipraz in people with Non-alcoholic Fatty Liver Disease, run by PharmaKing at 5 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 2 inclusion and 14 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 10 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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 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?
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?
MRS (time frame: 24 weeks). 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 NCT01373554, which also lists 2 linked publications.
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 10 Dec 2013; AzTrials last refreshed its copy on 8 Nov 2026.