Effect of Silymarin in Rheumatoid Arthritis Patients Treated With Methotrexate

December 6, 2024 updated by: Hend Mohsen Mohamed El-metwally, Tanta University

Clinical Study Evaluating Anti Rheumatic Activity and The Role of Silymarin in Attenuating Methotrexate Toxicity in Patients With Rheumatoid Arthritis

The goal of this clinical trial is to evaluate the anti-rheumatic activity and the role of silymarin in attenuating methotrexate toxicity in patients with rheumatoid arthritis.

Methodology:

This is a randomized, double blind placebo controlled parallel study that will be conducted on 44 patients with active rheumatoid arthritis.

Group1 (placebo group; n=22) which will receive IM or SC Methotrexate plus placebo tablet once daily for 3 months.

Group2 (Silymarin group; n=22) which will receive IM or SC Methotrexate plus Silymarin tablets 140 mg once daily for 3 months.

Duration: 3 months

Monitoring:

Participants will be followed up by weekly telephone calls and monthly direct meeting at scheduled visits to assess their adherence and to report any drug related adverse effects.

In summary, this clinical trial is designed to determine if Silymarin is a safe and effective treatment for Rheumatoid Arthritis Patients Treated with Methotrexate by comparing its effects to a placebo and closely monitoring participants throughout the study.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Rheumatoid arthritis (RA) is an autoimmune disorder in which immune systems mistakenly attacks the host body systems. Its clinical features are often characterized as chronic synovial non-infectious inflammation, cartilage, and bone destruction (1). Currently, no effective drugs can be used to cure RA in the clinic. For the treatment of RA, recommended medications include disease-modifying anti-rheumatic drugs (DMARDs) and biologic agents, which intend to achieve the remission of symptoms, but these medications also confer severe side effects when they exert therapeutic efficiency (2). Due to drug resistance and side effects, a big proportion of RA patients do not effectively respond to the treatment and urgently need new drugs or therapeutic strategies.

Approximate 60% of RA patients are overweight and suffering from metabolic disorders (3). Clinical features of lipid paradox often occur in active RA patients, leading to high risk of developing cardiovascular morbidity and mortality (4-6). In addition, the deregulated lipid metabolism is yet present in the early stage of RA and/or pre-RA (7). In recent years, lipid-lowering therapy with statins is demonstrated to be effective in RA treatment (8,9) and in the prevention of the dyslipidemia development in RA patients (10). In short, we can confirm that lipid metabolism must be implicated in the pathogenesis of RA, which conserves the drug-target capacity for therapeutic discovery against RA in the clinic, especially for overweight patients with dyslipidemia (10).

Silymarin, a major flavonoid from milk thistle (silymarin), has been used to treat many liver disorders, such as nonalcoholic steatohepatitis (NASH), cirrhosis, and liver cancer, based on its anti-oxidant, anti-inflammation, anti-fibro genetic and lipid-lowering pharmacological activities (11).

Overexpression of liver X receptor α (LXRα) and several key lipogenic enzymes regulated by LXRα, including lipoprotein lipase (LPL), cholesterol 7α and 27α hydroxylase (CYP7A, CYP27A), adipocyte fatty acid-binding protein (aP2/FABP4) and fatty acid translocase (CD36/FAT), were observed in AIA rats, which mostly accounted for dyslipidemia during arthritis development. Metabolomics, docking technology, and biochemical results indicated that antiarthritis effects of silymarin related to suppressing the up-regulated LXRα and abnormal lipid metabolism. Notably, activation of LXRα could potentiate cell inflammatory process induced by LPS (Lipopolysaccharide) through the regulation of NF-κB pathway, however, suppression of LXRα agonism by siRNA or silymarin reduced the nuclear translocation of NF-κB as well as the induction of downstream cytokines, indicating LXRα agonism is the important factor for the arthritis development and could be a potential target (12). Considering the priority of silymarin in drug-safety, and the potential in improving lipid metabolism, therefore our effort attempted to explore the therapeutic potential of silymarin against RA with dyslipidemia, effect of silymarin on lipid profile and lipoprotein lipase and decipher associated molecular mechanisms accordingly.

Methotrexate has remained the "anchor drug" for most patients since the late 1980s (13). However, despite its long-term and widespread use for RA, methotrexate induce liver and nephrotoxicity, In study done by Adel A Hagag et al, on 80 children with newly diagnosed Acute Lymphoblastic Leukemia (ALL) received Silymarin 420 mg/day in 3 divided doses for one week after each MTX dose indicate that Silymarin improved some hepatic and renal functions in children with ALL who received MTX-based chemotherapy protocols (14).

In the present study, we evaluate the lipid profile and the major lipid metabolic enzymes in rheumatoid arthritis patients treated with methotrexate, and further explore the effects of silymarin in ameliorating both arthritis, dyslipidemia, the underlying mechanism of silymarin against RA through the regulation of lipoprotein lipase / lipid metabolism as well as effect of silymarin on methotrexate liver and renal toxicity.

Study Type

Interventional

Enrollment (Estimated)

44

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Mansoura, Egypt, 35511
        • Outpatient Clinic of Internal Medicine, Rheumatology and Immunology Department, Mansoura University Hospital, Mansoura, 35511
        • Contact:
          • Hend Mohsen El-metwally, Bachelor of Pharmacy
          • Phone Number: +20 1026120017
          • Email: hmohsen@horus.edu.eg
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

  • Inclusion criteria:

    • Patients with active rheumatoid arthritis (not in remission) according to 28 joints disease activity score (DAS-28) >2.6.
    • Age range between 18 and 60 years old.
    • Both sexes.
    • Sex ratio, age, disease activity, and disease duration matched patients.
    • Patients receive methotrexate plus traditional therapy

  • Exclusion criteria:

    • Patients with renal or hepatic diseases (chronic liver disease, liver cirrhosis, alcoholic hepatitis, or chronic alcoholism).
    • Patients receiving biological DMARDs.
    • Patients with hypersensitivity to study medications.
    • Patients using antioxidants except silymarin.
    • Pregnant and lactating females.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: MTX S.C or IM _ Silymarin tab
IM or S.C MTX plus Silymarin 140 mg Tab once daily
Drug: MTX S.C or IM and Silymarin 140 mg tab
IM or S.C Methotrexate plus Silymarin tablets 140 mg once daily for 3 months.
Placebo Comparator: MTX S.C or IM _ Placebo tablet
IM or S.C MTX plus Placebo Tablet once daily
Drug: MTX S.C or IM
IM or SC Methotrexate plus placebo tablet once daily for 3 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Calculation of DAS-28-CRP score for measure disease activity.
Time Frame: From enrollment to the end of treatment at 3 months
This is a score for measure of disease activity in Rheumatoid Arthritis; Less than 2.6 mean RA is in remission, 2.6 to 3.2 mean low level of disease activity, More than 3.2 mean active disease that may require change in medication, More than 5.1 mean very active disease that requires careful monitoring and adjustment to medication
From enrollment to the end of treatment at 3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measurement of serum Nuclear factor kappa-B p65 (NF-κ B p65) & Lipoprotein lipase (LPL).
Time Frame: From enrollment to the end of treatment at 3 months

Before and 3 months after the intervention, 5 ml of venous blood will be withdrawn by antecubital venipuncture from each participant between 8:30 and 10:30 am. Blood samples will be transferred into a plain test tube and centrifuged at 3000 rpm for 10 min. the separated serum will be used for determination of: serum Nuclear factor kappa-B p65 (NF-κ B p65) & Lipoprotein lipase (LPL).

serum Nuclear factor kappa-B p65 (NF-κ B p65): one of the main inflammatory pathways in the Autoimmune Disease (AD) Rheumatoid Arthritis (RA), which exhibits high levels of inflammatory cytokines such as IL-1, TNFa and IL-6.

Lipoprotein lipase: Overexpression of liver X receptor α (LXRα) and several key lipogenic enzymes regulated by LXRα, including lipoprotein lipase (LPL) were observed in adjuvant-induced arthritis.
From enrollment to the end of treatment at 3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tanta University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

December 10, 2024

Primary Completion (Estimated)

March 10, 2025

Study Completion (Estimated)

April 10, 2025

Study Registration Dates

First Submitted

October 6, 2024

First Submitted That Met QC Criteria

December 6, 2024

First Posted (Estimated)

December 9, 2024

Study Record Updates

Last Update Posted (Estimated)

December 9, 2024

Last Update Submitted That Met QC Criteria

December 6, 2024

Last Verified

December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Effect of Silymarin in RA

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Rheumatoid Arthritis (RA)

Clinical Trials on MTX S.C or IM and Silymarin 140 mg tab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Argentina

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe