Effect of Silymarin in Rheumatoid Arthritis Patients Treated With Methotrexate

NCT06724952 | Not Yet Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: Effect of Silymarin in RA
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Rheumatoid Arthritis (RA)

Keywords

Rheumatoid Arthritis; Silymarin; Methotrexate

Outcome Measures

Primary Outcomes (1)

• Calculation of DAS-28-CRP score for measure disease activity.

  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 Outcomes (1)

• Measurement of serum Nuclear factor kappa-B p65 (NF-κ B p65) & Lipoprotein lipase (LPL).

  From enrollment to the end of treatment at 3 months

Study Arms (2)

MTX S.C or IM _ Silymarin tab

ACTIVE COMPARATOR

IM or S.C MTX plus Silymarin 140 mg Tab once daily

Drug: MTX S.C or IM and Silymarin 140 mg tab

MTX S.C or IM _ Placebo tablet

PLACEBO COMPARATOR

IM or S.C MTX plus Placebo Tablet once daily

Drug: MTX S.C or IM

Interventions

MTX S.C or IM and Silymarin 140 mg tab DRUG

IM or S.C Methotrexate plus Silymarin tablets 140 mg once daily for 3 months.

MTX S.C or IM _ Silymarin tab

MTX S.C or IM DRUG

IM or SC Methotrexate plus placebo tablet once daily for 3 months.

MTX S.C or IM _ Placebo tablet

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tanta University: lead

Study Sites (1)

Outpatient Clinic of Internal Medicine, Rheumatology and Immunology Department, Mansoura University Hospital, Mansoura, 35511

Al Mansurah, 35511, Egypt

Location

Related Publications (14)

• Hagag AA, Elgamsy MA, El-Asy HM, Mabrouk MM. Protective Role of Silymarin on Hepatic and Renal Toxicity Induced by MTX Based Chemotherapy in Children with Acute Lymphoblastic Leukemia. Mediterr J Hematol Infect Dis. 2016 Sep 1;8(1):e2016043. doi: 10.4084/MJHID.2016.043. eCollection 2016.

  PMID: 27648206 RESULT

• Weinblatt ME, Coblyn JS, Fox DA, Fraser PA, Holdsworth DE, Glass DN, Trentham DE. Efficacy of low-dose methotrexate in rheumatoid arthritis. N Engl J Med. 1985 Mar 28;312(13):818-22. doi: 10.1056/NEJM198503283121303.

  PMID: 3883172 RESULT

• Xie Y, Feng SL, Mai CT, Zheng YF, Wang H, Liu ZQ, Zhou H, Liu L. Suppression of up-regulated LXRalpha by silybin ameliorates experimental rheumatoid arthritis and abnormal lipid metabolism. Phytomedicine. 2021 Jan;80:153339. doi: 10.1016/j.phymed.2020.153339. Epub 2020 Sep 19.

  PMID: 33038868 RESULT

• Karimi G, Vahabzadeh M, Lari P, Rashedinia M, Moshiri M. "Silymarin", a promising pharmacological agent for treatment of diseases. Iran J Basic Med Sci. 2011 Jul;14(4):308-17.

  PMID: 23492971 RESULT

• Nurmohamed MT, Dijkmans BA. Dyslipidaemia, statins and rheumatoid arthritis. Ann Rheum Dis. 2009 Apr;68(4):453-5. doi: 10.1136/ard.2008.104497. No abstract available.

  PMID: 19286903 RESULT

• Soulaidopoulos S, Nikiphorou E, Dimitroulas T, Kitas GD. The Role of Statins in Disease Modification and Cardiovascular Risk in Rheumatoid Arthritis. Front Med (Lausanne). 2018 Feb 8;5:24. doi: 10.3389/fmed.2018.00024. eCollection 2018.

  PMID: 29473041 RESULT

• Das S, Mohanty M, Padhan P. Outcome of rheumatoid arthritis following adjunct statin therapy. Indian J Pharmacol. 2015 Nov-Dec;47(6):605-9. doi: 10.4103/0253-7613.169585.

  PMID: 26729950 RESULT

• Kerekes G, Nurmohamed MT, Gonzalez-Gay MA, Seres I, Paragh G, Kardos Z, Barath Z, Tamasi L, Soltesz P, Szekanecz Z. Rheumatoid arthritis and metabolic syndrome. Nat Rev Rheumatol. 2014 Nov;10(11):691-6. doi: 10.1038/nrrheum.2014.121. Epub 2014 Aug 5.

  PMID: 25090948 RESULT

• Giles JT, Allison M, Blumenthal RS, Post W, Gelber AC, Petri M, Tracy R, Szklo M, Bathon JM. Abdominal adiposity in rheumatoid arthritis: association with cardiometabolic risk factors and disease characteristics. Arthritis Rheum. 2010 Nov;62(11):3173-82. doi: 10.1002/art.27629.

  PMID: 20589684 RESULT

• Erum U, Ahsan T, Khowaja D. Lipid abnormalities in patients with Rheumatoid Arthritis. Pak J Med Sci. 2017 Jan-Feb;33(1):227-230. doi: 10.12669/pjms.331.11699.

  PMID: 28367205 RESULT

• Amezaga Urruela M, Suarez-Almazor ME. Lipid paradox in rheumatoid arthritis: changes with rheumatoid arthritis therapies. Curr Rheumatol Rep. 2012 Oct;14(5):428-37. doi: 10.1007/s11926-012-0269-z.

  PMID: 22802154 RESULT

• Roubenoff R, Roubenoff RA, Cannon JG, Kehayias JJ, Zhuang H, Dawson-Hughes B, Dinarello CA, Rosenberg IH. Rheumatoid cachexia: cytokine-driven hypermetabolism accompanying reduced body cell mass in chronic inflammation. J Clin Invest. 1994 Jun;93(6):2379-86. doi: 10.1172/JCI117244.

  PMID: 8200971 RESULT

• Guo Q, Wang Y, Xu D, Nossent J, Pavlos NJ, Xu J. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Res. 2018 Apr 27;6:15. doi: 10.1038/s41413-018-0016-9. eCollection 2018.

  PMID: 29736302 RESULT

• McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011 Dec 8;365(23):2205-19. doi: 10.1056/NEJMra1004965. No abstract available.

  PMID: 22150039 RESULT

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Silymarin

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Flavonolignans; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Teaching Assistant in clinical pharmacy at Horus University and master degree student

Study Record Dates

• First Submitted: October 6, 2024
• First Posted: December 9, 2024
• Study Start: December 10, 2024
• Primary Completion: March 10, 2025
• Study Completion: April 10, 2025
• Last Updated: December 9, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)