NCT05144217

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

Impact of Different Silymarin Dosages to Decrease Drug-induced Elevated Liver Enzymes Compared to Placebo in a Prospective Controlled Dose Finding Phase IIb Trial

• Status: Completed
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 19 (actual)
• Sponsor: Prof. Dr. Frank Behrens · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

In clinical routine care, drug-induced elevation of liver enzymes occurs often in parallel to new treatment initiation, possibly leading to interruption of treatment strategies if liver enzyme elevation does not normalize within 2 to 4 weeks. Liver injury from medications usually occurs within 6 months of drug initiation and typically within the first 1-4 weeks1. In general, drug-induced liver injury (DILI) is related to the class of drug, the quantity of drug consumed, the patient's age and sex, and such concurrent factors as diabetes mellitus, excessive alcohol intake, e.g. high caloric diet, which can lead to NAFLD/steatosis, or the use of other medications. Drugs administered in higher doses are more likely to cause liver injury, especially drugs that require extensive hepatic metabolism1. Different forms of drug-induced elevation of liver enzymes can be differentiated according to localisation of the injury: hepatocellular or cholestatic liver injury or a mixture of both.Besides methotrexate and isozid, other medications have been reported to induce hepatocellular liver injury: acarbose, allopurinol, amiodarone, baclofen, bupropion, fluoxetine, ketoconazole, lisinopril, losartan, non-steroidal anti-inflammatory drugs (NSAIDs), omeprazole, paracetamol, paroxetine, pyrazinamide, rifampicin, risperidone, sertraline, statins, tetracyclines, trazodone, and valproic acid. Silymarin containing oral preparations are widely used for their liver protecting characteristics. The milk thistle ingredient silibinin is registered for continuous intravenous administration in the case of acute liver intoxications such as consumption of amanita mushrooms. Although its mode of action is still not clear, the clinical therapeutic benefits in patients with liver diseases are documented. Pharmacokinetics of silymarin after oral administration are well understood. Due to its poor solubility in aqueous media, absorption from the intestinal tract is generally limited. Silymarin's systemic bioavailability of marketed products is therefore rather low, also because of predominant first pass biliary elimination. Exact PK/PD relations of the compound have not been assessed so far. Hence, in this clinical study silymarin will be administered in different dosages and compared to placebo in order to address the following question: Can liver protecting features of silymarin, measured by changes of liver enzyme concentration, 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

Interventions

Type	Name	Description
DRUG	Placebo	1 capsule per day of placebo
DRUG	2x 140 mg per day	2 capsule per day of silimarit
DRUG	3x 280 mg per day	3 capsule per day of silimarit
DRUG	1x 1120 mg	8 capsule per day of silimarit

Timeline

• Start date: 2021-06-23
• Primary completion: 2024-12-12
• Completion: 2024-12-15
• First posted: 2021-12-03
• Last updated: 2026-01-14

Locations

2 sites across 1 country: Germany