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

Arthritis, Rheumatoid Clinical Trial

Official title:

Comparison of Combination of Methotrexate and Statins With Methotrexate Alone as an Anti-inflammatory Agent in the Treatment of Rheumatoid Arthritis.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04177173
• Other study ID #: 5181/REG./KEMU/2017
• Status: Completed
• Phase: Phase 4
• Start date: September 1, 2017
• Est. completion date: December 14, 2018

Study information

• Verified date: November 2019
• Source: King Edward Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

After approval from Board of Studies and IRB of King Edward Medical University, all patients fulfilling inclusion and exclusion criteria from out patient department and wards of Mayo Hospital Lahore will be selected and randomized to group A or group B by lottery method (using coin flipping method) with one group receiving combination of methotrexate and simvastatin and other group receiving simvastatin only. All patients will be given adequate dose of analgesics for pain relief. Informed consent will be obtained from the patient. Demographic information like name, age and sex, will also be obtained. DAS 28 scoring will be done at the time of presentation and will be noted. Patients will be followed at 1 month, 3 month and at 6 month. At each follow up DAS 28(ESR) score will be calculated using DAS 28 calculator. All this information will be recorded on predesigned proforma (attached).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: December 14, 2018
• Est. primary completion date: December 14, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Drug:
• Simvastatin 20 mg
improvement of disease activity
• Methotrexate 10 mg
improvement of disease activity

Locations

Country	Name	City	State
Pakistan	Mayo Hospital	Lahore	Punjab

Sponsors (1)

Lead Sponsor	Collaborator
King Edward Medical University

Country where clinical trial is conducted

Pakistan, 

References & Publications (11)

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 — View Citation

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. Epub 2006 Mar 30. — View Citation

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. — View Citation

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 tetrahydrobio — View Citation

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. — View Citation

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. — View Citation

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. Ep — View Citation

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 — View Citation

McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011 Dec 8;365(23):2205-19. doi: 10.1056/NEJMra1004965. Review. — View Citation

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 — View Citation

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 — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Adverse Drug Reaction	Adverse event reported against any of the intervention under study	6 months