Methotrexate and Statins With Methotrexate Alone in the Treatment of Rheumatoid Arthritis

NCT04177173 | Completed Phase 4 DMC

• 1 other identifier: 5181/REG./KEMU/2017
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of the study is to compare the efficacy of combination of Methotrexate and Statins with Methotrexate alone in the treatment of Rheumatoid Arthritis. It is hypothesized that adding statins to methotrexate for treatment of rheumatic arthritis will significantly suppress the disease activity as compared to methotrexate alone.

Conditions

Arthritis, Rheumatoid

Keywords

Methotrexate; Statins; Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Efficacy of drugs defined by improvement in Disease Activity Score 28 (DAS28)

  In Rheumatoid arthritis, DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. A DAS 28 below the value of 2.6 is interpreted as Remission/improvement

  6 months

Secondary Outcomes (1)

• Adverse Drug Reaction

  6 months

Study Arms (2)

Simvastatin & Methotrexate

EXPERIMENTAL

Methotrexate 10 mg once a week per oral for 6 months and Statins (Simvastatin) 20 mg once a day per oral

Drug: Simvastatin 20 mg; Drug: Methotrexate 10 mg

Methotrexate

ACTIVE COMPARATOR

Methotrexate 10 mg once a week for 6 months

Drug: Methotrexate 10 mg

Interventions

Simvastatin 20 mg DRUG

improvement of disease activity

Simvastatin & Methotrexate

Methotrexate 10 mg DRUG

improvement of disease activity

Methotrexate; Simvastatin & Methotrexate

Eligibility Criteria

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

You may qualify if:

• All patients between ages 18 years and above
• Gender- Both male and female
• Fulfilling 2010 ACR/EULAR criteria of Rheumatoid arthritis with active inflammatory disease defined by DAS 28 score \>2.6,
• Normal serum cholesterol level.

You may not qualify if:

• Already diagnosed patients of Diabetes mellitus.
• Use of steroids greater than 4 weeks of duration or intra articular steroid injection within 4 weeks of study.
• Statin therapy in last three months.
• Statin intolerant patient.
• Elevated Creatinine Phosphokinase more than twice the upper limit of normal range.
• Diagnosed case of Chronic liver disease or abnormal liver functions (transaminases \> 2 times the upper limit of normal range) before the start of treatment or during follow-up.
• High serum Creatinine level
• Pregnancy and breast feeding.

Sponsors & Collaborators

• King Edward Medical University: lead

Study Sites (1)

Mayo Hospital

Lahore, Punjab Province, 54000, Pakistan

Location

Related Publications (11)

• Alam SM, Kidwai AA, Jafri SR, Qureshi BM, Sami A, Qureshi HH, Mirza H. Epidemiology of rheumatoid arthritis in a tertiary care unit, Karachi, Pakistan. J Pak Med Assoc. 2011 Feb;61(2):123-6.

  PMID: 21375157 BACKGROUND

• Wells G, Becker JC, Teng J, Dougados M, Schiff M, Smolen J, Aletaha D, van Riel PL. Validation of the 28-joint Disease Activity Score (DAS28) and European League Against Rheumatism response criteria based on C-reactive protein against disease progression in patients with rheumatoid arthritis, and comparison with the DAS28 based on erythrocyte sedimentation rate. Ann Rheum Dis. 2009 Jun;68(6):954-60. doi: 10.1136/ard.2007.084459. Epub 2008 May 19.

  PMID: 18490431 RESULT

• Mowla K, Rajai E, Ghorbani A, Dargahi-Malamir M, Bahadoram M, Mohammadi S. Effect of Atorvastatin on the Disease Activity and Severity of Rheumatoid Arthritis: Double-Blind Randomized Controlled Trial. J Clin Diagn Res. 2016 May;10(5):OC32-6. doi: 10.7860/JCDR/2016/16538.7814. Epub 2016 May 1.

  PMID: 27437268 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

• Aoki C, Nakano A, Tanaka S, Yanagi K, Ohta S, Jojima T, Kasai K, Takekawa H, Hirata K, Hattori Y. Fluvastatin upregulates endothelial nitric oxide synthase activity via enhancement of its phosphorylation and expression and via an increase in tetrahydrobiopterin in vascular endothelial cells. Int J Cardiol. 2012 Apr 5;156(1):55-61. doi: 10.1016/j.ijcard.2010.10.029. Epub 2010 Nov 18.

  PMID: 21093076 RESULT

• Abeles AM, Marjanovic N, Park J, Attur M, Chan ES, Al-Mussawir HE, Dave M, Fisher MC, Stuchin SA, Abramson SB, Pillinger MH. Protein isoprenylation regulates secretion of matrix metalloproteinase 1 from rheumatoid synovial fibroblasts: effects of statins and farnesyl and geranylgeranyl transferase inhibitors. Arthritis Rheum. 2007 Sep;56(9):2840-53. doi: 10.1002/art.22824.

  PMID: 17763406 RESULT

• Lazzerini PE, Lorenzini S, Selvi E, Capecchi PL, Chindamo D, Bisogno S, Ghittoni R, Natale MR, Caporali F, Giuntini S, Marcolongo R, Galeazzi M, Laghi-Pasini F. Simvastatin inhibits cytokine production and nuclear factor-kB activation in interleukin 1beta-stimulated synoviocytes from rheumatoid arthritis patients. Clin Exp Rheumatol. 2007 Sep-Oct;25(5):696-700.

  PMID: 18078616 RESULT

• Gazzerro P, Proto MC, Gangemi G, Malfitano AM, Ciaglia E, Pisanti S, Santoro A, Laezza C, Bifulco M. Pharmacological actions of statins: a critical appraisal in the management of cancer. Pharmacol Rev. 2012 Jan;64(1):102-46. doi: 10.1124/pr.111.004994. Epub 2011 Nov 21.

  PMID: 22106090 RESULT

• Agrawal S, Misra R, Aggarwal A. Autoantibodies in rheumatoid arthritis: association with severity of disease in established RA. Clin Rheumatol. 2007 Feb;26(2):201-4. doi: 10.1007/s10067-006-0275-5. Epub 2006 Mar 30.

  PMID: 16572283 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

• Dowman B, Campbell RM, Zgaga L, Adeloye D, Chan KY. Estimating the burden of rheumatoid arthritis in Africa: A systematic analysis. J Glob Health. 2012 Dec;2(2):020406. doi: 10.7189/jogh.02.020406.

  PMID: 23289081 RESULT

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Simvastatin; Methotrexate

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)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Rabia Rathore, FCPS

  Associate Professor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: April 7, 2019
• First Posted: November 26, 2019
• Study Start: September 1, 2017
• Primary Completion: December 14, 2018
• Study Completion: December 14, 2018
• Last Updated: November 26, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)