Silymarin's Advantage on Graft Effectiveness

NCT06801886 | Enrolling By Invitation Phase 3

• 1 other identifier: TNO_UNM
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (2)

• eGFR improvement

  Investigators estimate 1 month of silymarin supplementation may improve eGFR by 5 ml/min/1.73 m2 compared to palcebo at 3 months. Assuming a standard deviation of 10 ml/min/1.73 m2, a two-sided aplha of 0.005, and 80 % power, a sample size 64 participants per group is required.

  3 months

• Inicidence of biopsy proven acute rejection

  Investigators assume - by supplementing silymarine the incidence of BPAR diagnosed by 3rd month protocolar biopsy, will be lower.

  6 months

Secondary Outcomes (3)

• Incidence of PTDM

  6 months

• Incidence of dyslipidemia

  6 months

• Improved graft function in participatns with delayed graft function

  6 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Patients suplemented with placebo

Other: Placebo Supplementation

Silymarin

EXPERIMENTAL

Patients suplemented with silymarin

Drug: Silymarine supplementation

Interventions

Silymarine supplementation DRUG

900 mg of silymarin supplementation daily during the early post-transplant period, (for 30 days) under standard treatment.

Silymarin

Placebo Supplementation OTHER

Placebo supplementation during the early post-transplant period (30 days) under standard treatment

Placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Martin: lead

Study Sites (1)

University Hospital Martin

Martin, 036 01, Slovakia

Location

Related Publications (4)

• 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.

  PMID: 31092990 BACKGROUND

• 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.

  PMID: 19590824 BACKGROUND

• 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.

  PMID: 30834633 BACKGROUND

• 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.

  PMID: 27340676 BACKGROUND

MeSH Terms

Conditions

Hypertension; Renal Insufficiency, Chronic

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: ass.prof., MD, Ph.D.

Study Record Dates

• First Submitted: January 24, 2025
• First Posted: January 30, 2025
• Study Start: January 7, 2020
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

SL (1)