Arthritis, RheumatoidPhase 4NCT04177173
Methotrexate and Statins With Methotrexate Alone in the Treatment of Rheumatoid Arthritis
A Phase 4 study testing Simvastatin 20 mg and Methotrexate 10 mg in people with Arthritis, Rheumatoid, run by King Edward Medical University at 1 site in Pakistan.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Arthritis, Rheumatoid
- What is being tested?
- Simvastatin 20 mg and Methotrexate 10 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 sitePakistan
- Study dates
- 1 Sep 2017to 14 Dec 2018
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Comparison of Combination of Methotrexate and Statins With Methotrexate Alone as an Anti-inflammatory Agent in the Treatment of Rheumatoid Arthritis.
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.
Read the detailed 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).
- Conditions
- Arthritis, Rheumatoid
- Being tested
- Simvastatin 20 mg, Methotrexate 10 mg
- Keywords
- Methotrexate, Statins, Rheumatoid Arthritis
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Simvastatin 20 mgDrug
improvement of disease activity
Methotrexate 10 mgDrug
improvement of disease activity
| Study group | Role | What they receive |
|---|---|---|
| Simvastatin & Methotrexate | Experimental | Methotrexate 10 mg once a week per oral for 6 months and Statins (Simvastatin) 20 mg once a day per oral Receives: Drug: Simvastatin 20 mg; Drug: Methotrexate 10 mg |
| Methotrexate | Active comparator | Methotrexate 10 mg once a week for 6 months Receives: Drug: Methotrexate 10 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 6 months
Secondary outcomes (1)
Adverse Drug Reaction
Adverse event reported against any of the intervention under study
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 posted26 Nov 2019
- Study start1 Sep 2017
- Primary completion14 Dec 2018
- Study completion14 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Arthritis, RheumatoidStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- King Edward Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rabia Rathore, King Edward Medical University
- Investigators
- Rabia Rathore, FCPS, Principal investigator, Associate Professor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04177173
- Sponsor's protocol ID
- 5181/REG./KEMU/2017
- Status last verified
- Nov 2019
- First submitted
- 7 Apr 2019
- Last updated
- 26 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 21375157Wells 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.
PubMed 18490431Mowla 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.
PubMed 27437268Das 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.
PubMed 26729950Aoki 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.
PubMed 21093076Abeles 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.
PubMed 17763406Lazzerini 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.
PubMed 18078616Gazzerro 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.
PubMed 22106090Agrawal 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.
PubMed 16572283McInnes 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.
PubMed 22150039Dowman 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.
PubMed 23289081
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Combination of Methotrexate and Statins With Methotrexate Alone as an Anti-inflammatory Agent in the Treatment of Rheumatoid Arthritis.
- ClinicalTrials.gov ID
- NCT04177173
- Acronym / sponsor ID
- 5181/REG./KEMU/2017
- Conditions
- Arthritis, Rheumatoid
- Keywords
- Methotrexate, Statins, Rheumatoid Arthritis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- King Edward Medical UniversityUniversity, hospital or other
- Study start
- 1 Sep 2017 (actual)
- Primary completion
- 14 Dec 2018 (actual)
- Study completion
- 14 Dec 2018 (actual)
- First posted
- 26 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Simvastatin & Methotrexate | Experimental | Drug: Simvastatin 20 mg, Drug: Methotrexate 10 mgMethotrexate 10 mg once a week per oral for 6 months and Statins (Simvastatin) 20 mg once a day per oral |
| Methotrexate | Active comparator | Drug: Methotrexate 10 mgMethotrexate 10 mg once a week for 6 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Simvastatin 20 mgimprovement of disease activity | Drug | Simvastatin & Methotrexate |
| Methotrexate 10 mgimprovement of disease activity | Drug | Methotrexate, Simvastatin & Methotrexate |
Primary outcome
Efficacy of drugs defined by improvement in Disease Activity Score 28 (DAS28)
Time frame: 6 months
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
1 secondary outcome
Adverse Drug Reaction
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2019.
- Background: PubMed 21375157Alam 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.
- Results publication: PubMed 18490431Wells 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.
- Results publication: PubMed 27437268Mowla 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.
- Results publication: PubMed 26729950Das 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.
- Results publication: PubMed 21093076Aoki 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.
- Results publication: PubMed 17763406Abeles 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.
- Results publication: PubMed 18078616Lazzerini 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.
- Results publication: PubMed 22106090Gazzerro 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.
- Results publication: PubMed 16572283Agrawal 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.
- Results publication: PubMed 22150039McInnes 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.
- Results publication: PubMed 23289081Dowman 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rabia Rathore, FCPS principal investigator
Associate Professor
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Simvastatin 20 mg and Methotrexate 10 mg in people with Arthritis, Rheumatoid, run by King Edward Medical University at 1 site in Pakistan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of drugs defined by improvement in Disease Activity Score 28 (DAS28) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04177173, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2019.