Non-alcoholic Fatty Liver DiseasePhase 2NCT02006498
Silymarin for the Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD)
A Phase 2 study testing Sillymarin in people with Non-alcoholic Fatty Liver Disease, run by University of Malaya at 1 site in Malaysia.
Trial summary
This is a randomised study to examine whether high dose Sillymarin will be able to help improve fat-induced liver damage in the liver. The study hypothesis is that high dose Sillymarin will be able to reduce steato-hepatitis (fat-related liver inflammation) better than placebo. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-alcoholic Fatty Liver Disease
- What is being tested?
- Sillymarin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 99 participants
- Where
- 1 siteMalaysia
- Study dates
- Jun 2012to Dec 2015
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female 18 years of age or older.
- Diagnosed with NASH (refer to Section 5.2)
- AST and/or ALT greater than 40 IU/L.
- Must agree to adhere to alcohol consumption guideline.
- Weight gain//loss of no more than 10% between biopsy and screening or within 30 days of screening if the biopsy is performed during the screening period.
- No change in diabetic and/or lipid medications between biopsy and screening or within 30 days of screening if the biopsy is performed during the screening period
Who cannot join
- Use of silymarin or other milk thistle preparations for a period of 90 consecutive days or longer between biopsy and initial screening, or within 30 days prior to screening if the biopsy is performed during the screening period.
- Use of other antioxidants or non-prescribed complementary alternative medications for a period of 90 consecutive days or longer between biopsy and initial screening, or within 30 days prior to screening if the biopsy is performed during the screening period.
- Use of warfarin, metronidazole, or acetaminophen (greater than 2 grams per day) between screening and randomization.
- Use of oral steroids for more than 14 days of screening or prior to randomization.
- BMI ≥ 35 kg/m2 between screening and randomization.
- Poorly-controlled diabetes (HbA1c > 8 %) between screening and randomization
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- Diabetes mellitus treated with oral agents other than the secretagogues or metformin between screening and randomization. Sitagliptin is allowed.
- For patients using anti-hyperlipidemic agents or accepted anti-diabetic agents, any change of agent or dose between screening and randomization.
- Radiologic imaging consistent with cirrhosis or portal hypertension.
- Evidence of decompensated liver disease
- Platelet count < 130 x 109 /L at screening.
- History of bariatric surgery, or undergoing evaluation for bariatric surgery.
- Known allergy/sensitivity to milk thistle or its preparations.
- History of immunologically mediated disease
- History of thyroid disease poorly controlled on prescribed medications.
- History of solid organ or bone marrow transplantation.
- Primary hepatic malignancy.
- Secondary hepatic malignancy or extrahepatic malignancy.
- Serum Creatinine of 176 μmol/L or greater or creatinine clearance (calculated according to Cockcroft-Gault) 60 mL/min or less, or on dialysis, at screening.
- Severe illness or any other conditions that would make the patient, in the opinion of the investigator, unsuitable for the study.
- Women with ongoing pregnancy or breast feeding, or contemplating pregnancy.
- Women of childbearing potential who are not practicing an acceptable form of birth control.
- Participation in a research drug trial within 30 days of screening.
- Inability or unwillingness to give informed consent or abide by the study protocol.
Trial locations and contacts
1 site in 1 country.
Malaysia1 site
University Malaya Medical Centre
Kuala Lumpur, Kuala Lumpur, 59100
About this study
Official title: A Randomised, Double-blind, Placebo-controlled, Phase II, Single-centre Study to Assess the Safety and Efficacy of Silymarin 700 mg Capsules TID for the Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD)
This is a randomised study to examine whether high dose Sillymarin will be able to help improve fat-induced liver damage in the liver. The study hypothesis is that high dose Sillymarin will be able to reduce steato-hepatitis (fat-related liver inflammation) better than placebo.
Read the detailed description
OBJECTIVES OF STUDY Primary Objectives
- To assess the safety and adverse event profile of Silymarin compared to placebo.
- To assess the efficacy of Silymarin as defined by an improvement in non-alcoholic steatosis (NAS) activity score by at least 30% from baseline compared to placebo.
Secondary Objectives
- To compare NAS activity before and after Silymarin therapy.
- To characterize changes in ALT and AST during Silymarin therapy.
- To compare insulin resistance measured by HOMAr during Silymarin therapy.
- Conditions
- Non-alcoholic Fatty Liver Disease
- Being tested
- Sillymarin, Placebo
- Keywords
- non-alcoholic fatty liver disease, sillymarin, randomised trial, non-alcoholic steatohepatitis
- 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.
SillymarinDrug
Also called Legalon
Sillymarin is derived from the milk thistle plant, Silybum marianum, a herbal remedy that has been used for centuries for diseases of the liver. It is a complex mixture of 6 major flavonolignans (silybins A and B, isosilybins A and B, silychristin, and silydianin), as well as other minor polyphenolic compounds.
PlaceboDrug
Placebo capsule with same appearances as study drug
| Study group | Role | What they receive |
|---|---|---|
| Sillymarin | Experimental | Active component study medication Receives: Drug: Sillymarin |
| Placebo | Placebo comparator | Placebo capsules Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the efficacy of Silymarin as defined by an improvement in non-alcoholic steatosis (NAS) activity score by at least 30% from baseline compared to placebo
Measured: 12 months
Secondary outcomes (1)
To assess the safety and adverse event profile of Silymarin compared to placebo
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2013 (estimated)
- Study startJun 2012
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- More trials run by University of MalayaThe sponsor's other registered studies.
- 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
- 99 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Malaya
- Sponsor type
- University, hospital or other
- Collaborators
- Rottapharm
- Responsible party
- Sponsor
- Investigators
- Sanjiv Mahadeva, MD, MRCP, Principal investigator, University of Malaya
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02006498
- Sponsor's protocol ID
- LE13T0.01
- Status last verified
- Jan 2016
- First submitted
- 4 Dec 2013
- Last updated
- 8 Jan 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Wah Kheong C, Nik Mustapha NR, Mahadeva S. A Randomized Trial of Silymarin for the Treatment of Nonalcoholic Steatohepatitis. Clin Gastroenterol Hepatol. 2017 Dec;15(12):1940-1949.e8. doi: 10.1016/j.cgh.2017.04.016. Epub 2017 Apr 15.
PubMed 28419855
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-blind, Placebo-controlled, Phase II, Single-centre Study to Assess the Safety and Efficacy of Silymarin 700 mg Capsules TID for the Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD)
- ClinicalTrials.gov ID
- NCT02006498
- Acronym / sponsor ID
- LE13T0.01
- Conditions
- Non-alcoholic Fatty Liver Disease
- Keywords
- non-alcoholic fatty liver disease, sillymarin, randomised trial, non-alcoholic steatohepatitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 99 participants (actual)
- Lead sponsor
- University of MalayaUniversity, hospital or other
- Collaborators
- Rottapharm
- Study start
- Jun 2012
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 10 Dec 2013 (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.
This is a randomised study to examine whether high dose Sillymarin will be able to help improve fat-induced liver damage in the liver. The study hypothesis is that high dose Sillymarin will be able to reduce steato-hepatitis (fat-related liver inflammation) better than placebo.
Detailed description
OBJECTIVES OF STUDY Primary Objectives
- To assess the safety and adverse event profile of Silymarin compared to placebo.
- To assess the efficacy of Silymarin as defined by an improvement in non-alcoholic steatosis (NAS) activity score by at least 30% from baseline compared to placebo.
Secondary Objectives
- To compare NAS activity before and after Silymarin therapy.
- To characterize changes in ALT and AST during Silymarin therapy.
- To compare insulin resistance measured by HOMAr during Silymarin therapy.
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 |
|---|---|---|
| Sillymarin | Experimental | Drug: SillymarinActive component study medication |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo capsules |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female 18 years of age or older.
- Diagnosed with NASH (refer to Section 5.2)
- AST and/or ALT greater than 40 IU/L.
- Must agree to adhere to alcohol consumption guideline.
- Weight gain//loss of no more than 10% between biopsy and screening or within 30 days of screening if the biopsy is performed during the screening period.
Key exclusion criteria (24 listed)
- Use of silymarin or other milk thistle preparations for a period of 90 consecutive days or longer between biopsy and initial screening, or within 30 days prior to screening if the biopsy is performed during the screening period.
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 |
|---|---|---|
| SillymarinAlso: LegalonSillymarin is derived from the milk thistle plant, Silybum marianum, a herbal remedy that has been used for centuries for diseases of the liver. It is a complex mixture of 6 major flavonolignans (silybins A and B, isosilybins A and B, silychristin, and silydianin), as well as other minor polyphenolic compounds. | Drug | Sillymarin |
| PlaceboPlacebo capsule with same appearances as study drug | Drug | Placebo |
Primary outcome
To assess the efficacy of Silymarin as defined by an improvement in non-alcoholic steatosis (NAS) activity score by at least 30% from baseline compared to placebo
Time frame: 12 months
1 secondary outcome
To assess the safety and adverse event profile of Silymarin compared to placebo
Time frame: 12 months
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 8 Jan 2016.
- Derived from this study: PubMed 28419855Wah Kheong C, Nik Mustapha NR, Mahadeva S. A Randomized Trial of Silymarin for the Treatment of Nonalcoholic Steatohepatitis. Clin Gastroenterol Hepatol. 2017 Dec;15(12):1940-1949.e8. doi: 10.1016/j.cgh.2017.04.016. Epub 2017 Apr 15.
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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.
Sanjiv Mahadeva, MD, MRCP principal investigator
University of Malaya
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sillymarin in people with Non-alcoholic Fatty Liver Disease, run by University of Malaya at 1 site in Malaysia.
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 6 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: finished, as of the sponsor's last update on 8 Jan 2016. 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 Malaysia. 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?
To assess the efficacy of Silymarin as defined by an improvement in non-alcoholic steatosis (NAS) activity score by at least 30% from baseline compared to placebo (time frame: 12 months). 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 NCT02006498, 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 8 Jan 2016.