Posttransplant Diabetes MellitusPhase 3SAGENCT06801886
Silymarin's Advantage on Graft Effectiveness
A Phase 3 study testing Silymarine supplementation in people with Posttransplant Diabetes Mellitus and Acute Graft Rejection, run by University Hospital, Martin at 1 site in Slovakia.
Trial 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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Posttransplant Diabetes Mellitus, Acute Graft Rejection, Biopsy Proven Acute Rejection
- What is being tested?
- Silymarine supplementation
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 130 participants
- Where
- 1 siteSlovakia
- Study dates
- 7 Jan 2020to 31 Dec 2025
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Effect of Silymarin Supplementation on Graft Function and Early Post-transplant Complications
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
- Being tested
- Silymarine supplementation, Placebo Supplementation
- Keywords
- silymarin, biopsy proven acute rejection, dnDSA, PTDM, protocolar biopsy, kidney transplantation
- Medical subject headings
- Hypertension, Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Silymarine supplementationDrug
900 mg of silymarin supplementation daily during the early post-transplant period, (for 30 days) under standard treatment.
Placebo SupplementationOther
Placebo supplementation during the early post-transplant period (30 days) under standard treatment
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Patients suplemented with placebo Receives: Other: Placebo Supplementation |
| Silymarin | Experimental | Patients suplemented with silymarin Receives: Drug: Silymarine supplementation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 6 months
Secondary outcomes (3)
Incidence of PTDM
Investigators asssume by supplementing silymarine, the incidence of PTDM diagnosed according to 2024 guidelines will be lower in observed period.
Measured: 6 months
Incidence of dyslipidemia
Investigators asssume by supplementing silymarine, the incidence of hypercholesterolemia or dyslipidemia will be lower in observed period.
Measured: 6 months
Improved graft function in participatns with delayed graft function
Investigators assume that in the group of patients with DGF, those supplemented with silymarine will have better eGFR and graft function during the observed period.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2025
- Study start7 Jan 2020
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Posttransplant Diabetes MellitusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Care provider
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Martin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Matej Vnucak, University Hospital, Martin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06801886
- Sponsor's protocol ID
- TNO_UNM
- Acronym
- SAGE
- Status last verified
- Mar 2025
- First submitted
- 24 Jan 2025
- Last updated
- 30 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31092990Kaur 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.
PubMed 19590824Mohammadi 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.
PubMed 30834633Voroneanu 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.
PubMed 27340676