Clinical trial NCT06801886: Silymarin's Advantage on Graft Effectiveness
Official title: Effect of Silymarin Supplementation on Graft Function and Early Post-transplant Complications
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE3
Conditions: Posttransplant Diabetes Mellitus
Acute Graft Rejection
Biopsy Proven Acute Rejection
Antibody Mediated Rejection of Kidney Transplant
Arterial Hypertension, Chronic Kidney Disease
Keywords: silymarin
biopsy proven acute rejection
dnDSA
PTDM
protocolar biopsy
kidney transplantation
Lead sponsor: University Hospital, Martin
Sponsor class: OTHER
First posted: 2025-01-30
Enrollment: 130
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The study examines the impact of silymarin supplementation during the early post-transplant period, administering 900 g daily for 30 days under standard treatment. Subsequently, the investigators investigate its impact on graft function, as measured by eGFR (CKD-EPI equation), UACR or UPCR, the development of dnDSA, rejection changes, and histological changes in the 3-month biopsy protocol. At the same time, investigators will investigate the effect of silymarin on metabolic complications-PTDM, DLP, disorders of calcium-phosphate metabolism, and arterial hypertension in the post-transplant period-in comparison with the placebo group. At the same time, investigators will investigate the safety and tolerance of silymarin.


Eligibility criteria: Inclusion Criteria:

* First or second kidney transplant recipient
* Deceased or living donor kidney transplant
* Patients receiving standard immunosuppression regimen:
* Tacrolimus or cyclosporine + Mycophenolate mofetil + Corticosteroids
* Body Mass Index (BMI) 18-35 kg/m²
* Willingness to provide informed consent
* Ability to understand and comply with study procedures
* Stable medical condition without significant comorbidities

Exclusion Criteria:

* Multi-organ transplant recipients
* Recipients of ABO-incompatible or highly sensitized transplants
* Active infectious complications at the time of transplantation: HIV, Active hepatitis B or C, Active cytomegalovirus (CMV) infection
* Patients with known liver disease: Cirrhosis, Active hepatitis, ALT or AST \> 2.5 times the upper limit of normal
* Significant cardiovascular disease: Recent myocardial infarction (within 6 months), Unstable angina, Severe heart failure (NYHA Class III or IV)
* Malignancy within the past 5 years (except successfully treated non-melanoma skin cancer)
* Current or recent (within 30 days) participation in another clinical trial
* Pregnancy or planned pregnancy during the study period
* Known allergy or hypersensitivity to silymarin or milk thistle
* Patients taking medications with significant interactions with silymarin:

Anticoagulants, Cytochrome P450 enzyme modulators

* Psychiatric conditions that may interfere with study compliance
* Uncontrolled diabetes mellitus (HbA1c \> 8.5%)
* History of non-compliance with medical treatment
* Patients with known genetic disorders affecting drug metabolism

Primary outcomes:
measure: eGFR improvement
timeFrame: 3 months
measure: Inicidence of biopsy proven acute rejection
timeFrame: 6 months
Secondary outcomes:
measure: Incidence of PTDM
timeFrame: 6 months
measure: Incidence of dyslipidemia
timeFrame: 6 months
measure: Improved graft function in participatns with delayed graft function
timeFrame: 6 months
Other outcomes:
Locations:
city: Martin
country: Slovakia
facility: University Hospital Martin
Study officials:
References:
citation: Goli F, Karimi J, Khodadadi I, Tayebinia H, Kheiripour N, Hashemnia M, Rahimi R. Silymarin Attenuates ELMO-1 and KIM-1 Expression and Oxidative Stress in the Kidney of Rats with Type 2 Diabetes. Indian J Clin Biochem. 2019 Apr;34(2):172-179. doi: 10.1007/s12291-018-0735-0. Epub 2018 Feb 6.
citation: Kaur G, Athar M, Alam MS. Dietary supplementation of silymarin protects against chemically induced nephrotoxicity, inflammation and renal tumor promotion response. Invest New Drugs. 2010 Oct;28(5):703-13. doi: 10.1007/s10637-009-9289-6. Epub 2009 Jul 10.
citation: Mohammadi H, Hadi A, Arab A, Moradi S, Rouhani MH. Effects of silymarin supplementation on blood lipids: A systematic review and meta-analysis of clinical trials. Phytother Res. 2019 Apr;33(4):871-880. doi: 10.1002/ptr.6287. Epub 2019 Mar 5.
citation: Voroneanu L, Nistor I, Dumea R, Apetrii M, Covic A. Silymarin in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Diabetes Res. 2016;2016:5147468. doi: 10.1155/2016/5147468. Epub 2016 Jun 1.