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Phase II Trial of Silymarin for Non-Cirrhotic Patients With Non-Alcoholic Steatohepatitis (SyNCH)

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ClinicalTrials.gov Identifier: NCT00680407
Recruitment Status : Completed
First Posted : May 20, 2008
Results First Posted : January 29, 2016
Last Update Posted : July 17, 2019
Sponsor:
Collaborators:
University of Pennsylvania
University of North Carolina
Thomas Jefferson University
Beth Israel Deaconess Medical Center
Brooke Army Medical Center
University of Pittsburgh
Information provided by (Responsible Party):
Madaus Inc

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Non-alcoholic Steatohepatitis
Interventions Other: Placebo
Drug: Silymarin 700 mg
Drug: Silymarin 420 mg
Enrollment 78
Recruitment Details Patients were recruited at 5 sites; first observation April 30, 2008, last observation Nov 12, 2012.
Pre-assignment Details  
Arm/Group Title Silymarin 420 mg Silymarin 700 mg Placebo
Hide Arm/Group Description

420 mg Legalon (silymarin) three times daily

Silymarin 420 mg: 420 mg dose (5 pills, three times daily) for 48-50 week treatment period

700 mg of Legalon (silymarin) three times daily

Silymarin 700 mg: 700 mg dose (5 pills, three times daily) for 48-50 week treatment period

Placebo (lactose pill)

Placebo: Placebo (5 pills, three times daily) for 48-50 week treatment period

Period Title: Overall Study
Started 26 27 25
Completed 18 22 22
Not Completed 8 5 3
Reason Not Completed
Lost to Follow-up             3             3             1
Withdrawal by Subject             5             2             2
Arm/Group Title Silymarin 420 mg Silymarin 700 mg Placebo Total
Hide Arm/Group Description

420 mg Legalon (silymarin) three times daily

Silymarin 420 mg: 420 mg dose (5 pills, three times daily) for 48-50 week treatment period

700 mg of Legalon (silymarin) three times daily

Silymarin 700 mg: 700 mg dose (5 pills, three times daily) for 48-50 week treatment period

Placebo (lactose pill)

Placebo: Placebo (5 pills, three times daily) for 48-50 week treatment period

Total of all reporting groups
Overall Number of Baseline Participants 26 27 25 78
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 26 participants 27 participants 25 participants 78 participants
47.3  (10.83) 48.2  (11.43) 49.51  (10.89) 48.3  (10.95)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants 27 participants 25 participants 78 participants
Female
13
  50.0%
9
  33.3%
11
  44.0%
33
  42.3%
Male
13
  50.0%
18
  66.7%
14
  56.0%
45
  57.7%
1.Primary Outcome
Title Efficacy - Improvement by at Least 2 Points in Histology (NAS)
Hide Description Histological Scoring System for Nonalcoholic Fatty Liver Disease ranges from 0-8 with the increase in number representing a worse outcome. Therefore the efficacy improvement was to be at least 2 points in lowering the score.
Time Frame 48-50 week treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Silymarin 420 mg Silymarin 700 mg Placebo
Hide Arm/Group Description:

420 mg Legalon (silymarin) three times daily

Silymarin 420 mg: 420 mg dose (5 pills, three times daily) for 48-50 week treatment period

700 mg of Legalon (silymarin) three times daily

Silymarin 700 mg: 700 mg dose (5 pills, three times daily) for 48-50 week treatment period

Placebo (lactose pill)

Placebo: Placebo (5 pills, three times daily) for 48-50 week treatment period

Overall Number of Participants Analyzed 26 27 25
Measure Type: Number
Unit of Measure: participants
5 4 3
2.Secondary Outcome
Title Safety - Occurrence of a Dose-limiting Toxicity
Hide Description [Not Specified]
Time Frame 48-50 week treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Silymarin 420 mg Silymarin 700 mg Placebo
Hide Arm/Group Description:

420 mg Legalon (silymarin) three times daily

Silymarin 420 mg: 420 mg dose (5 pills, three times daily) for 48-50 week treatment period

700 mg of Legalon (silymarin) three times daily

Silymarin 700 mg: 700 mg dose (5 pills, three times daily) for 48-50 week treatment period

Placebo (lactose pill)

Placebo: Placebo (5 pills, three times daily) for 48-50 week treatment period

Overall Number of Participants Analyzed 26 27 25
Measure Type: Number
Unit of Measure: participants
2 0 0
3.Post-Hoc Outcome
Title Efficacy - Improvement by at Least 2 Points in Histology (NAS) - With NAS Without Cirrhosis
Hide Description This outcome measure excludes the substantial percentage (62.8%) of patients with baseline biopsies that were deemed ineligible (per inclusion criteria) by the central pathologist due to NAS <4 or absence of NASH (nonalcoholic steatohepatitis) (n=34), NASH with presence of cirrhosis (n=1), or slides unavailable/not evaluable for reading (n=14).
Time Frame 48-50 week treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
Subgroup of ITT (Intent to Treat) Patients with NASH and without cirrhosis population
Arm/Group Title Silymarin 420 mg Silymarin 700 mg Placebo
Hide Arm/Group Description:

420 mg Legalon (silymarin) three times daily

Silymarin 420 mg: 420 mg dose (5 pills, three times daily) for 48-50 week treatment period

700 mg of Legalon (silymarin) three times daily

Silymarin 700 mg: 700 mg dose (5 pills, three times daily) for 48-50 week treatment period

Placebo (lactose pill)

Placebo: Placebo (5 pills, three times daily) for 48-50 week treatment period

Overall Number of Participants Analyzed 10 9 10
Measure Type: Number
Unit of Measure: participants
3 4 1
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Silymarin 420 mg Silymarin 700 mg Placebo
Hide Arm/Group Description

420 mg Legalon (silymarin) three times daily

Silymarin 420 mg: 420 mg dose (5 pills, three times daily) for 48-50 week treatment period

700 mg of Legalon (silymarin) three times daily

Silymarin 700 mg: 700 mg dose (5 pills, three times daily) for 48-50 week treatment period

Placebo (lactose pill)

Placebo: Placebo (5 pills, three times daily) for 48-50 week treatment period

All-Cause Mortality
Silymarin 420 mg Silymarin 700 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Silymarin 420 mg Silymarin 700 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/26 (3.85%)      2/27 (7.41%)      1/25 (4.00%)    
Blood and lymphatic system disorders       
LOW PLATELET COUNT *  0/26 (0.00%)  0 1/27 (3.70%)  1 0/25 (0.00%)  0
Hepatobiliary disorders       
ACUTE HEMATOMA POST TREATMENT LIVER BIOPSY *  1/26 (3.85%)  1 0/27 (0.00%)  0 0/25 (0.00%)  0
Musculoskeletal and connective tissue disorders       
BACK SURGERY L5/S1 *  0/26 (0.00%)  0 0/27 (0.00%)  0 1/25 (4.00%)  1
Nervous system disorders       
HOSPITALIZED FOR SEVERE HEADACHE *  0/26 (0.00%)  0 1/27 (3.70%)  1 0/25 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Silymarin 420 mg Silymarin 700 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   17/26 (65.38%)      14/27 (51.85%)      11/25 (44.00%)    
Cardiac disorders       
Cardiac *  3/26 (11.54%)  1/27 (3.70%)  2/25 (8.00%) 
Gastrointestinal disorders       
Gasto-intestinal *  5/26 (19.23%)  4/27 (14.81%)  4/25 (16.00%) 
General disorders       
Headache *  2/26 (7.69%)  1/27 (3.70%)  2/25 (8.00%) 
Investigations       
Hyperglycemia *  1/26 (3.85%)  2/27 (7.41%)  0/25 (0.00%) 
Musculoskeletal and connective tissue disorders       
Musculoskeletal *  2/26 (7.69%)  1/27 (3.70%)  4/25 (16.00%) 
Nervous system disorders       
Depression *  1/26 (3.85%)  2/27 (7.41%)  1/25 (4.00%) 
Psychiatric disorders       
Neurological *  0/26 (0.00%)  1/27 (3.70%)  2/25 (8.00%) 
Renal and urinary disorders       
Urological *  1/26 (3.85%)  1/27 (3.70%)  2/25 (8.00%) 
Respiratory, thoracic and mediastinal disorders       
Respiratory *  2/26 (7.69%)  3/27 (11.11%)  2/25 (8.00%) 
Skin and subcutaneous tissue disorders       
Dermatologic *  0/26 (0.00%)  2/27 (7.41%)  1/25 (4.00%) 
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Associate Director, Clinical Research and Operations
Organization: Meda Pharmaceuticals, Inc.
EMail: michael.purzycki@meda.us
Layout table for additonal information
Responsible Party: Madaus Inc
ClinicalTrials.gov Identifier: NCT00680407     History of Changes
Other Study ID Numbers: U01AT003566-02 ( U.S. NIH Grant/Contract )
IND 105,461 (orig. IND 74,887) ( Other Identifier: FDA Investigational New Drug Application )
First Submitted: May 15, 2008
First Posted: May 20, 2008
Results First Submitted: December 23, 2015
Results First Posted: January 29, 2016
Last Update Posted: July 17, 2019