Chronic Hepatitis CPhase 2SyNCHNCT00680342
Phase II Trial of Silymarin for Patients With Chronic Hepatitis C Who Have Failed Conventional Antiviral Treatment
A Phase 2 study testing Silymarin in people with Chronic Hepatitis C, run by National Center for Complementary and Integrative Health (NCCIH) at 5 sites in United States.
Trial summary
Silymarin (Legalon), also known as milk thistle, is an alternative medicine commonly found in health food and vitamin stores. People with liver disease sometimes use silymarin because it is thought to have liver protecting effects; however, this benefit has not been proven. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Hepatitis C
- What is being tested?
- Silymarin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 154 participants
- Where
- 5 sitesUnited States
- Study dates
- Apr 2008to Jan 2011
- 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
- Age at least 18 years at screening.
- Serum HCV RNA above quantifiable level of detection by any assay after the end of previous therapy.
- ALT > 65 IU/L (i.e., approximately 1.5 X upper limit of normal) obtained during the screening period.
- Previous treatment with any interferon-based therapy without sustained virological response.
- Negative urine pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of silymarin. Females of childbearing potential must be using two reliable forms of effective contraception during the study (while on drug and during follow-up).
Who cannot join
- Use of silymarin or other milk thistle preparations within 30 days prior to screening.
- Use of other antioxidants such as vitamin E, vitamin C, glutathione, alpha-tocopherol, or non-prescribed complementary alternative medications (including dietary supplements, megadose vitamins, herbal preparations, and special teas) within 30 days prior to screening. A multivitamin at standard doses will be allowed.
- Use of silymarin or other antioxidants or non-prescribed complementary alternative medications (as above) during the screening period or patient unwilling to refrain from taking these medications through completion of the study.
- Any antiviral therapy within 6 months prior to screening visit.
- Known allergy/sensitivity to milk thistle or its preparations.
- Evidence of poorly-controlled diabetes (defined as HbA1c > 8% in patients with diabetes).
Show all 23Show fewer
- Use of warfarin, metronidazole or acetaminophen (greater than two grams per day) within 30 days of screening.
- Lactose intolerance defined as patient reported inability to tolerate milk products.
- Previous liver biopsy that demonstrated presence of moderate to severe steatosis or evidence of steatohepatitis.
- Positive test for anti-HIV or HBsAg within 5 years of screening.
- Average alcohol consumption of more than one drink or equivalent (>12 grams) per day or more than two (2) drinks on any one day over the 30 days prior to screening. Patients who met either criterion more than 30 days ago must have consumed a monthly average of 12 grams or less per day of alcohol for at least six months prior to screening.
- History of other chronic liver disease, including metabolic diseases, documented by appropriate test(s).
- Women with ongoing pregnancy or breast-feeding, or contemplating pregnancy.
- Serum creatinine level 2.0 mg/dL or greater at screening or CrCl ≤ 60cc/min, or currently on dialysis. The creatinine clearance (CrCl) will be calculated according to Cockcroft-Gault.
- Evidence of drug abuse within 6 months prior to screening or during the screening period.
- Evidence of decompensated liver disease defined as any of the following: serum albumin <3.2 g/dl, total bilirubin > 1.5 mg/dl, or PT/INR > 1.3 times normal at screening, or history or presence of ascites or encephalopathy, or bleeding from esophageal varices.
- History or other evidence of severe illness or any other conditions that would make the patient, in the opinion of the investigator, unsuitable for the study (such as poorly controlled psychiatric disease, coronary artery disease, or active gastrointestinal conditions that might interfere with drug absorption).
- History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hepatitis, autoimmune hemolytic anemia, severe psoriasis, rheumatoid arthritis) that could affect inflammatory biomarkers.
- History of solid organ or bone marrow transplantation.
- History of thyroid disease poorly controlled on prescribed medications.
- Use of oral steroids for more than 14 days within 30 days prior to screening.
- Participation in a research drug trial, exclusive of the SyNCH Phase I trial, within 6 months of enrollment.
- Inability or unwillingness to provide informed consent or abide by the study protocol.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 00215
University of North Carolina
Chapel Hill, North Carolina, 27599
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
About this study
Official title: A Multicenter, Randomized, Double-masked, Placebo-controlled Phase II Study to Assess the Safety and Efficacy of a Standardized Orally Administered Silymarin Preparation (Legalon) for the Treatment of Patients With Chronic Hepatitis C Who Failed Conventional Antiviral Therapy
Silymarin (Legalon), also known as milk thistle, is an alternative medicine commonly found in health food and vitamin stores. People with liver disease sometimes use silymarin because it is thought to have liver protecting effects; however, this benefit has not been proven. The purpose of this research study is to determine the effectiveness of silymarin and assess the safety of different silymarin doses in patients with varying severity of liver disease compared to a placebo (lactose pill).
Eligible subjects will be randomized to treatment with placebo or one of two dosages of Legalon® 420 mg or 700 mg administered orally thrice daily. Investigators and subjects will be masked to treatment assignment. The study design includes a screening period during which patients will undergo full medical evaluation to verify protocol eligibility and a treatment period of 24 weeks during which time clinic visits and laboratory studies will be performed every 2-4 weeks to monitor for safety and efficacy of therapy. Subjects will continue to be followed for an additional 12 weeks after the completion of study medication to monitor for adverse events and investigate post-treatment outcomes. Participation in this research study requires the subject to travel to the clinic for at least 10 visits so recruitment will be limited to a geographically restricted area around participating clinical centers.
Read the detailed description
This proposal is a phase II study that will evaluate the safety and efficacy of silymarin for the treatment of subjects with chronic hepatitis C who did not respond to conventional antiviral therapy. The primary objectives of this study are to assess the safety and adverse event profile of silymarin over a range of doses compared to placebo and to assess efficacy of silymarin in normalizing serum aminotransferase activity in patients with chronic hepatitis C. Secondary objectives are to characterize the effect of silymarin on serum levels of HCV RNA and to explore relationships between silymarin therapy and serum biomarkers of HCV hepatic disease activity (oxidative stress, apoptosis, and fibrogenesis).
- Conditions
- Chronic Hepatitis C
- Being tested
- Silymarin, Placebo
- Keywords
- hepatitis C
- Medical subject headings
- Hepatitis C, Chronic, Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SilymarinDrug
Also called Legalon, milk thistle
700mg dose (5 pills, three times daily) for 24-week treatment period
SilymarinDrug
Also called Legalon, milk thistle
420mg dose (5 pills, three times daily) for 24-week treatment period
PlaceboOther
Also called lactose pill
Placebo (5 pills, three times daily) for 24-week treatment period
| Study group | Role | What they receive |
|---|---|---|
| 1 | Placebo comparator | Placebo (lactose pill) Receives: Other: Placebo |
| 2 | Experimental | 700mg of Legalon (silymarin) three times daily Receives: Drug: Silymarin |
| 3 | Experimental | 420mg Legalon (silymarin) three times daily Receives: Drug: Silymarin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy - whether or not serum ALT (mg/dl) is less than or equal to 45 IU/L (approximate normal range) or achieves at least 50% decline to less than 65 IU/L (approximately 1.5 times the upper limit of normal)
Measured: 24-week treatment period
Safety - occurence of a dose-limiting toxicity
Measured: 24-week treatment period
Secondary outcomes (2)
Adherence - summary of missed dose information obtained from patient diaries and dose counts
Measured: 24 week treatment period
Biomarkers - the following relationships will be explored: dose and change in biomarkers, changes in biomarkers and rate of treatment success, change in biomarkers and rate of toxicity
Measured: 24 week treatment period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2008 (estimated)
- Study startApr 2008
- Primary completionJan 2011
- Study completionJan 2011
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 Chronic Hepatitis CStudies 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
- 154 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Center for Complementary and Integrative Health (NCCIH)
- Sponsor type
- US National Institutes of Health
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), University of Pennsylvania, University of North Carolina, Chapel Hill, Thomas Jefferson University, Beth Israel Deaconess Medical Center, University of Pittsburgh
- Responsible party
- Sponsor
- Investigators
- Michael Fried, MD, Principal investigator, University of North Carolina, Chapel HillVictor Navarro, MD, Principal investigator, Thomas Jefferson UniversityNezam Afdhal, MD, Principal investigator, Beth Israel Deaconess Medical CenterK. Rajender Reddy, MD, Principal investigator, University of PennsylvaniaSteven Belle, PhD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00680342
- Sponsor's protocol ID
- U01AT003566
- Other IDs
- IND 74,887
- Acronym
- SyNCH
- Status last verified
- Mar 2013
- First submitted
- 15 May 2008
- Last updated
- 18 Mar 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Reddy KR, Belle SH, Fried MW, Afdhal N, Navarro VJ, Hawke RL, Wahed AS, Doo E, Meyers CM; SyNCH Study Group. Rationale, challenges, and participants in a Phase II trial of a botanical product for chronic hepatitis C. Clin Trials. 2012 Feb;9(1):102-12. doi: 10.1177/1740774511427064. Epub 2011 Nov 4.
PubMed 22058086Fried MW, Navarro VJ, Afdhal N, Belle SH, Wahed AS, Hawke RL, Doo E, Meyers CM, Reddy KR; Silymarin in NASH and C Hepatitis (SyNCH) Study Group. Effect of silymarin (milk thistle) on liver disease in patients with chronic hepatitis C unsuccessfully treated with interferon therapy: a randomized controlled trial. JAMA. 2012 Jul 18;308(3):274-82. doi: 10.1001/jama.2012.8265.
PubMed 22797645
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-masked, Placebo-controlled Phase II Study to Assess the Safety and Efficacy of a Standardized Orally Administered Silymarin Preparation (Legalon) for the Treatment of Patients With Chronic Hepatitis C Who Failed Conventional Antiviral Therapy
- ClinicalTrials.gov ID
- NCT00680342
- Acronym / sponsor ID
- SyNCH / U01AT003566
- Conditions
- Chronic Hepatitis C
- Keywords
- hepatitis C
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 154 participants (actual)
- Lead sponsor
- National Center for Complementary and Integrative Health (NCCIH)US National Institutes of Health
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), University of Pennsylvania, University of North Carolina, Chapel Hill, Thomas Jefferson University, Beth Israel Deaconess Medical Center, University of Pittsburgh
- Study start
- Apr 2008
- Primary completion
- Jan 2011 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 20 May 2008 (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.
Silymarin (Legalon), also known as milk thistle, is an alternative medicine commonly found in health food and vitamin stores. People with liver disease sometimes use silymarin because it is thought to have liver protecting effects; however, this benefit has not been proven. The purpose of this research study is to determine the effectiveness of silymarin and assess the safety of different silymarin doses in patients with varying severity of liver disease compared to a placebo (lactose pill).
Eligible subjects will be randomized to treatment with placebo or one of two dosages of Legalon® 420 mg or 700 mg administered orally thrice daily. Investigators and subjects will be masked to treatment assignment. The study design includes a screening period during which patients will undergo full medical evaluation to verify protocol eligibility and a treatment period of 24 weeks during which time clinic visits and laboratory studies will be performed every 2-4 weeks to monitor for safety and efficacy of therapy. Subjects will continue to be followed for an additional 12 weeks after the completion of study medication to monitor for adverse events and investigate post-treatment outcomes. Participation in this research study requires the subject to travel to the clinic for at least 10 visits so recruitment will be limited to a geographically restricted area around participating clinical centers.
Detailed description
This proposal is a phase II study that will evaluate the safety and efficacy of silymarin for the treatment of subjects with chronic hepatitis C who did not respond to conventional antiviral therapy. The primary objectives of this study are to assess the safety and adverse event profile of silymarin over a range of doses compared to placebo and to assess efficacy of silymarin in normalizing serum aminotransferase activity in patients with chronic hepatitis C. Secondary objectives are to characterize the effect of silymarin on serum levels of HCV RNA and to explore relationships between silymarin therapy and serum biomarkers of HCV hepatic disease activity (oxidative stress, apoptosis, and fibrogenesis).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Placebo comparator | Other: PlaceboPlacebo (lactose pill) |
| 2 | Experimental | Drug: Silymarin700mg of Legalon (silymarin) three times daily |
| 3 | Experimental | Drug: Silymarin420mg Legalon (silymarin) three times daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age at least 18 years at screening.
- Serum HCV RNA above quantifiable level of detection by any assay after the end of previous therapy.
- ALT > 65 IU/L (i.e., approximately 1.5 X upper limit of normal) obtained during the screening period.
- Previous treatment with any interferon-based therapy without sustained virological response.
- Negative urine pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of silymarin. Females of childbearing potential must be using two reliable forms of effective contraception during the study (while on drug and during follow-up).
Key exclusion criteria (23 listed)
- Use of silymarin or other milk thistle preparations within 30 days prior to screening.
- Use of other antioxidants such as vitamin E, vitamin C, glutathione, alpha-tocopherol, or non-prescribed complementary alternative medications (including dietary supplements, megadose vitamins, herbal preparations, and special teas) within 30 days prior to screening. A multivitamin at standard doses will be allowed.
- Use of silymarin or other antioxidants or non-prescribed complementary alternative medications (as above) during the screening period or patient unwilling to refrain from taking these medications through completion of the study.
- Any antiviral therapy within 6 months prior to screening visit.
- Known allergy/sensitivity to milk thistle or its preparations.
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 |
|---|---|---|
| SilymarinAlso: Legalon, milk thistle700mg dose (5 pills, three times daily) for 24-week treatment period | Drug | 2 |
| SilymarinAlso: Legalon, milk thistle420mg dose (5 pills, three times daily) for 24-week treatment period | Drug | 3 |
| PlaceboAlso: lactose pillPlacebo (5 pills, three times daily) for 24-week treatment period | Other | 1 |
Primary outcome
Efficacy - whether or not serum ALT (mg/dl) is less than or equal to 45 IU/L (approximate normal range) or achieves at least 50% decline to less than 65 IU/L (approximately 1.5 times the upper limit of normal)
Time frame: 24-week treatment period
Safety - occurence of a dose-limiting toxicity
Time frame: 24-week treatment period
2 secondary outcomes
Adherence - summary of missed dose information obtained from patient diaries and dose counts
Time frame: 24 week treatment period
Biomarkers - the following relationships will be explored: dose and change in biomarkers, changes in biomarkers and rate of treatment success, change in biomarkers and rate of toxicity
Time frame: 24 week treatment period
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 18 Mar 2013.
- Background: PubMed 22058086Reddy KR, Belle SH, Fried MW, Afdhal N, Navarro VJ, Hawke RL, Wahed AS, Doo E, Meyers CM; SyNCH Study Group. Rationale, challenges, and participants in a Phase II trial of a botanical product for chronic hepatitis C. Clin Trials. 2012 Feb;9(1):102-12. doi: 10.1177/1740774511427064. Epub 2011 Nov 4.
- Results publication: PubMed 22797645Fried MW, Navarro VJ, Afdhal N, Belle SH, Wahed AS, Hawke RL, Doo E, Meyers CM, Reddy KR; Silymarin in NASH and C Hepatitis (SyNCH) Study Group. Effect of silymarin (milk thistle) on liver disease in patients with chronic hepatitis C unsuccessfully treated with interferon therapy: a randomized controlled trial. JAMA. 2012 Jul 18;308(3):274-82. doi: 10.1001/jama.2012.8265.
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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.
Michael Fried, MD principal investigator
University of North Carolina, Chapel Hill
Victor Navarro, MD principal investigator
Thomas Jefferson University
Nezam Afdhal, MD principal investigator
Beth Israel Deaconess Medical Center
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 Silymarin in people with Chronic Hepatitis C, run by National Center for Complementary and Integrative Health (NCCIH) at 5 sites in United States.
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 5 inclusion and 23 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 18 Mar 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 United States. 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?
Efficacy - whether or not serum ALT (mg/dl) is less than or equal to 45 IU/L (approximate normal range) or achieves at least 50% decline to less than 65 IU/L (approximately 1.5 times the upper limit of normal) (time frame: 24-week treatment period). The study lists 2 primary outcomes in all. 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 NCT00680342, 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 18 Mar 2013.