Cilostazol and Methotrexate in Rheumatoid Arthritis

NCT05594680 | Recruiting Phase 3

• 1 other identifier: cilostazol in rheumatoid
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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).

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (3)

• 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\*√(Tender joint count28) +0.28\*√(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

• 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

• 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 Outcomes (4)

• Change in the serum level of the assessed biological marker C-reactive protein

  Baseline,12weeks

• Change in the serum level of the assessed biological marker Nuclear factor kabba-B p65

  Baseline,12weeks

• Change in the serum level of the assessed biological marker Hemeoxygenase-1

  Baseline,12weeks

• Change in the serum level of the assessed biological marker Cyclic adenosine monophosphate

  Baseline,12weeks

Other Outcomes (1)

• Numbers of participants with treatment-related adverse events

  Baseline,12weeks

Study Arms (2)

Cilostazol and Methotrexate

ACTIVE COMPARATOR

Participants in this arm will receive Cilostazol 50 mg twice daily with Methotrexate for rheumatoid arthritis for 12 weeks.

Drug: Cilostazol; Drug: Methotrexate

Placebo and Methotrexate

PLACEBO COMPARATOR

Participants in this arm will receive Placebo with Methotrexate for rheumatoid arthritis for 12 weeks.

Drug: Methotrexate; Drug: Placebo

Interventions

Cilostazol DRUG

Cilostazol 50 MG

Cilostazol and Methotrexate

Methotrexate DRUG

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.

Cilostazol and Methotrexate; Placebo and Methotrexate

Placebo DRUG

Placebo

Placebo and Methotrexate

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tanta University: lead

Study Sites (1)

Faculty of medicine

Al Mansurah, Egypt

RECRUITING

Related Publications (5)

• 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.

  PMID: 22820172 BACKGROUND

• 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.

  PMID: 26170060 BACKGROUND

• 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.

  PMID: 17265482 BACKGROUND

• 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.

  PMID: 20131233 BACKGROUND

• Eldadamony SM, El-Haggar SM, Ali AMA, Mostafa TM. Clinical study evaluating the efficacy and safety of Cilostazol as an adjuvant therapy to methotrexate on patients with rheumatoid arthritis. Inflammopharmacology. 2025 Jun;33(6):3499-3508. doi: 10.1007/s10787-025-01782-2. Epub 2025 May 16.

  PMID: 40380042 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Cilostazol; 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)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Aminopterin; Pterins; Pteridines

Central Study Contacts

Samar Mahmoud Eldadamouny, Pharmacist

CONTACT

+201008456735; samer.abdelfattah99@gmail.com

Tarek Mohamed Mostafa, Professor

CONTACT

+201154594035; tarek.mostafa@pharm.tanta.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Pharmacist

Study Record Dates

• First Submitted: October 18, 2022
• First Posted: October 26, 2022
• Study Start: October 1, 2022
• Primary Completion: November 1, 2024
• Study Completion: November 1, 2024
• Last Updated: April 10, 2024

Record last verified: 2024-04

Locations

EG (1)