Impact of Silymarin Dosages to Decrease Drug-induced Elevated Liver Enzymes Compared to Placebo

NCT05144217 | Completed Phase 2

• 1 other identifier: TMP-2501-2019-2
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

Brief Summary

In this clinical study silymarin will be administered in different dosages and compared to placebo in order to address if the liver protecting features of silymarin, measured by changes of liver enzyme concentration, can be improved in patients with drug-induced elevated liver enzymes or drug-induced hepatocellular liver injury with higher systemic bioavailabilities due to administration of higher oral dosages or administration of higher administration frequency over a 35-day treatment period.

Conditions

Drug-induced Liver Injury

Keywords

silymarin

Outcome Measures

Primary Outcomes (1)

• Change in blood ALT (Alanine-Aminotransferase) in IU/L

  Change in blood ALT in IU/Lin all treatment groups

  at day 35

Secondary Outcomes (116)

• Liver enzyme blood parameter AST (Aspartate-Aminotransferase)

  Baseline (prior treatment)

• Liver enzyme blood parameter AST

  Day 7

• Liver enzyme blood parameter AST

  Day 14

• Liver enzyme blood parameters: AST

  Day 21

• Liver enzyme blood parameter AST

  Day 28

Study Arms (4)

Placebo

PLACEBO COMPARATOR

1 capsule twice per day

Drug: Placebo

oral administration of 2x 140 mg per day

ACTIVE COMPARATOR

1 capsule twice per day

Drug: 2x 140 mg per day

oral administration of 3x 280 mg per day

ACTIVE COMPARATOR

2 capsules three times a day

Drug: 3x 280 mg per day

oral administration of 1x 1120 mg per day

ACTIVE COMPARATOR

8 capsules once per day

Drug: 1x 1120 mg

Interventions

Placebo DRUG

1 capsule per day of placebo

Placebo

2x 140 mg per day DRUG

2 capsule per day of silimarit

oral administration of 2x 140 mg per day

3x 280 mg per day DRUG

3 capsule per day of silimarit

oral administration of 3x 280 mg per day

1x 1120 mg DRUG

8 capsule per day of silimarit

oral administration of 1x 1120 mg per day

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Evidence of hepatocellular drug-induced injury due to treatment\*
• ALT/AP ratio ≥ 5 ((ALT level/ALT upper limit of normal (ULN))/(AP level/AP ULN)) OR Evidence of drug-induced elevation of liver-enzymes
• ALT \> 40 U/L and ≤ 2 x ULN

You may not qualify if:

• Use of silymarin within the last 6 months
• Current intake and intake within the last 4 weeks of drugs that have been shown to induce cholestatic or mixed hepatocellular/cholestatic liver injury (inducing cholestatic liver injury: amoxicilline and clavulanic acid, anabolic steroids, chlorpromazine, clopidogrel, erythromycin, irbesartan, mirtazapine, estrogen, terbinafine; inducing mixed liver injury: amitriptyline, azathioprine, captopril, carbamazepine, clindamycin, co-trimoxazole, cyproheptadine, enalapril, flutamide, nitrofurantoin, phenobarbital, phenytoin, sulphonamide, trazodone, verapamil)
• Patients with chronic liver disease, existing fibrosis or cirrhosis
• Patients with acute viral hepatitis, autoimmune hepatitis or immune-mediated hepatitis (e.g., with immune checkpoint inhibitor treatment), acute Budd-Chiari syndrome, Wilson disease, and ischemic liver injury
• Cholestatic or mixed hepatocellular/mixed liver injury
• Patients with diabetes types 1 or 2
• Any malignancy within the past 5 years
• Patients with chronic intestinal diseases (e.g., ulcerative colitis) and intestinal barrier dysfunction in the discretion of the treating physician (e.g., patient can be included if disease is judged as stable by the treating physician with no likely interference with the study outcomes and the safety of the patient)
• Evidence of significant uncontrolled concomitant diseases or serious and/or uncontrolled diseases that are likely to interfere with the evaluation of the patient's safety and of the study outcome
• History of relevant central nervous system (CNS) and/or psychiatric disorders and/or currently treated CNS and/or psychiatric disorders
• Known allergic reactions to the active ingredients used or to constituents of the pharmaceutical preparations, e.g. milk thistle, soy oil, peanut (according to Summary of Product Characteristics (SmPc))
• Contraindications to use the investigational medicinal product (IMP), e.g. hereditary galactose intolerance, genetic lactase deficiency or glucose-galactose malabsorption (according to SmPC)
• Subjects with severe or moderate allergies or multiple drug allergies unless it is judged as not relevant for the clinical trial by the investigator
• Laboratory values other than target parameters out of normal range unless the deviation from normal is judged as not relevant for the clinical trial by the investigator
• Positive anti-HIV-test, antiHBs- or anti-HCV-test at Screening

Sponsors & Collaborators

• Prof. Dr. Frank Behrens: lead
• Bionorica SE: collaborator

Study Sites (2)

Universtity Hospital - clinic for dermatology, venerology and allergology

Frankfurt, Hessia, 60590, Germany

Location

CIRI

Frankfurt, Hessia, 60596, Germany

Location

MeSH Terms

Conditions

Chemical and Drug Induced Liver Injury

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Poisoning

Study Officials

• Stephan Schaefer, MD

  Fraunhofer ITMP

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: study medication and placebo are provided in identical blister
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor representative

Model Details: prospective placebo-controlled dose-finding study

Study Record Dates

• First Submitted: November 21, 2021
• First Posted: December 3, 2021
• Study Start: June 23, 2021
• Primary Completion: December 12, 2024
• Study Completion: December 15, 2024
• Last Updated: January 14, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)