Cilostazol and Methotrexate in Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

Official title:

The Phosphodiesterase 3 Inhibitor Cilostazol as Adjunct to Methotrexate in Patients With Rheumatoid Arthritis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05594680
• Other study ID #: cilostazol in rheumatoid
• Status: Recruiting
• Phase: Phase 3
• Start date: October 1, 2022
• Est. completion date: November 1, 2024

Study information

• Verified date: April 2024
• Source: Tanta University
• Contact: Samar Mahmoud Eldadamouny, Pharmacist
• Phone: +201008456735
• Email: samer.abdelfattah99[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims at evaluating the therapeutic effects of Cilostazol as adjuvant therapies to low dose of Methotrexate in patients with Rheumatoid Arthritis and to evaluate their impact on Cyclic adenosine monophosphate(CAMP), Heme Oxygenase-1(HO-1).

Description:

Rheumatoid arthritis (RA) is characterized by the presence of hyperplastic synovium in association with immune-mediated inflammatory synovitis associated with chronic production of proinflammatory cytokines, which lead to cartilage and bone degradation .This study is a randomized, controlled double blind placebo-controlled ,prospective study to evaluate the potential therapeutic effects of Cilostazol on synovial inflammation when administered as add-on treatments to the low dose of Methotrexate.

A total of 70 RA patients with active disease will be recruited from Outpatient Clinic of Physical Medicine, Rheumatology and Rehabilitation at Mansoura University hospitals, Mansoura, Egypt will be included in the study. They will be diagnosed with RA according to the American College of Rheumatology/European League Against Rheumatism criteria 2010 (the ACR/EULAR 2010 criteria).

RA Patients who will meet the inclusion criteria will be enrolled in the study.

They will be classified into two groups:

Group 1: 35 RA patients who will receive Methotrexate and placebo for 12 weeks and serve as the control group.

Group 2: 35 RA patients who will receive Methotrexate and Cilostazol 50 mg twice daily for 12 weeks.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: November 1, 2024
• Est. primary completion date: November 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Patients with active rheumatoid arthritis (not in remission) according to American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria (13) i.e 28 joints disease activity score (DAS-28) >2.6.

• Age range between 18 and 60 years old.

• Patients receive methotrexate; approximately the same doses of non steroidal anti-inflammatory drugs, selective cyclooxygenase-2 inhibitors, acetaminophen, and low dose of oral corticosteroids (Prednisolone < 15 mg) will be allowed to enroll the trial.

• Intravenous, intra-articular or intramuscular corticosteroids; intra articular hyaluronate sodium; biological DMARDs and other conventional DMARDs will not be permitted less than 4 weeks before the first dose of cilostazol.

Exclusion Criteria:

• Patients with diabetes, congestive heart failure, other heart disease (arrhythmia, hypertension, ischemic heart diseases), severe anemia, bleeding problems, other inflammatory diseases, active infection, other illness except rheumatoid arthritis.

• Patients on low doses of aspirin

• Patients on anticoagulants.

• Patients with renal or hepatic diseases.

• Patients receiving oral prednisolone greater than 15 mg/day.

• Patients receiving biological DMARDs.

• Patients with hypersensitivity to study medications.

• Patients using antioxidants .

• Pregnant and lactating females.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Cilostazol
Cilostazol 50 MG
• Methotrexate
Methotrexate (MTX) is the first-line therapy for treatment of RA patients. MTX suppresses proliferation of synovial fibroblasts, modulates cytokine synthesis and superoxide anion production, and inhibits neutrophil chemotaxis.
• Placebo
Placebo

Locations

Country	Name	City	State
Egypt	Faculty of medicine	Mansoura

Sponsors (1)

Lead Sponsor	Collaborator
Tanta University

Country where clinical trial is conducted

Egypt, 

References & Publications (4)

Kim HY, Lee SW, Park SY, Baek SH, Lee CW, Hong KW, Kim CD. Efficacy of concurrent administration of cilostazol and methotrexate in rheumatoid arthritis: pharmacologic and clinical significance. Life Sci. 2012 Sep 17;91(7-8):250-7. doi: 10.1016/j.lfs.2012.07.003. Epub 2012 Jul 20. — View Citation

Kirino Y, Takeno M, Murakami S, Kobayashi M, Kobayashi H, Miura K, Ideguchi H, Ohno S, Ueda A, Ishigatsubo Y. Tumor necrosis factor alpha acceleration of inflammatory responses by down-regulating heme oxygenase 1 in human peripheral monocytes. Arthritis Rheum. 2007 Feb;56(2):464-75. doi: 10.1002/art.22370. — View Citation

Park SY, Lee SW, Kim HY, Lee SY, Lee WS, Hong KW, Kim CD. Suppression of RANKL-induced osteoclast differentiation by cilostazol via SIRT1-induced RANK inhibition. Biochim Biophys Acta. 2015 Oct;1852(10 Pt A):2137-44. doi: 10.1016/j.bbadis.2015.07.007. Epub 2015 Jul 11. — View Citation

Park SY, Lee SW, Shin HK, Chung WT, Lee WS, Rhim BY, Hong KW, Kim CD. Cilostazol enhances apoptosis of synovial cells from rheumatoid arthritis patients with inhibition of cytokine formation via Nrf2-linked heme oxygenase 1 induction. Arthritis Rheum. 2010 Mar;62(3):732-41. doi: 10.1002/art.27291. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Numbers of participants with treatment-related adverse events	The adverse events in each group will be observed and documented during the whole procedure to show the safety of the treatment.	Baseline,12weeks
Primary	change in DAS-28 CRP score	Clinical assessment by calculating of 28-joint count Disease Activity score (DAS-28) using C-reactive protein according to calculating formula(DAS28 (CRP) = 0.56*v(Tender joint count28) +0.28*v(Sowallen joint count28)+0.36*ln (CRP+1)*1.10+1.15 will done where high disease activity = 5.1, low disease activity; = 3.2, and remission < 2.6.	Baseline,12 weeks
Primary	Change in Multi Dimensional Health Assessment score	Functional assessment will be assessed through Multi Dimensional Health Assessment score that include 14 items Health Assessment Questionaire .The score of the HAQ Questionnaire is calculated from the mean of the sum of the responses of the items where each item is scored from 0-3, where 0 = without any difficulty, 1; = with some difficulty, 2 = with much difficulty, and 3 = unable to do. in addition, MDHAQ includes the assessment of morning stiffness (MS) duration in minutes.	Baseline,12weeks
Primary	Change in Visual analog scale for pain	Visual analog scales which ranges from 0 to 10,it is a psychometric scale that is generally used in hospitals and clinics by doctors to conduct pain scale surveys to understand varying degrees of pain or discomfort experienced by a patient.	Baseline,12 weeks
Secondary	Change in the serum level of the assessed biological marker C-reactive protein	C-reactive protein :CRP value (normal range <1.0 mg/dl). If the value is increased, the disease activity worsened. If the value is reduced the disease activity is improved.	Baseline,12weeks
Secondary	Change in the serum level of the assessed biological marker Nuclear factor kabba-B p65	Transcriptional factor involved intracellular responses to stimuli and stress .So If the value is increased, the disease activity worsened. If the value is reduced the disease activity is improved.	Baseline,12weeks
Secondary	Change in the serum level of the assessed biological marker Hemeoxygenase-1	Hemeoxygenase-1 .	Baseline,12weeks
Secondary	Change in the serum level of the assessed biological marker Cyclic adenosine monophosphate	Cyclic adenosine monophosphate level.	Baseline,12weeks