Clinical trial NCT05594680: Cilostazol and Methotrexate in Rheumatoid Arthritis
Official title: The Phosphodiesterase 3 Inhibitor Cilostazol as Adjunct to Methotrexate in Patients With Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Tanta University
Sponsor class: OTHER
First posted: 2022-10-26
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: change in DAS-28 CRP score
timeFrame: Baseline,12 weeks
measure: Change in Multi Dimensional Health Assessment score
timeFrame: Baseline,12weeks
measure: Change in Visual analog scale for pain
timeFrame: Baseline,12 weeks
Secondary outcomes:
measure: Change in the serum level of the assessed biological marker C-reactive protein
timeFrame: Baseline,12weeks
measure: Change in the serum level of the assessed biological marker Nuclear factor kabba-B p65
timeFrame: Baseline,12weeks
measure: Change in the serum level of the assessed biological marker Hemeoxygenase-1
timeFrame: Baseline,12weeks
measure: Change in the serum level of the assessed biological marker Cyclic adenosine monophosphate
timeFrame: Baseline,12weeks
Other outcomes:
measure: Numbers of participants with treatment-related adverse events
timeFrame: Baseline,12weeks
Locations:
city: Mansoura
country: Egypt
facility: Faculty of medicine
Study officials:
References:
citation: 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.
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.
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.
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.