Back to resultsCilostazol and Methotrexate in Rheumatoid Arthritis
Primary Purpose
Rheumatoid Arthritis
Status
Recruiting
Phase
Phase 3
Locations
Egypt
Study Type
Interventional
Intervention
Cilostazol
Methotrexate
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis
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.
Sites / Locations
- Faculty of medicineRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Cilostazol and Methotrexate
Placebo and Methotrexate
Arm Description
Participants in this arm will receive Cilostazol 50 mg twice daily with Methotrexate for rheumatoid arthritis for 12 weeks.
Participants in this arm will receive Placebo with Methotrexate for rheumatoid arthritis for 12 weeks.
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
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.
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.
Change in the serum level of the assessed biological marker Hemeoxygenase-1
Hemeoxygenase-1 .
Change in the serum level of the assessed biological marker Cyclic adenosine monophosphate
Cyclic adenosine monophosphate level.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05594680
Brief Title
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
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 1, 2022 (Actual)
Primary Completion Date
November 1, 2023 (Anticipated)
Study Completion Date
February 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Tanta University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
70 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cilostazol and Methotrexate
Arm Type
Active Comparator
Arm Description
Participants in this arm will receive Cilostazol 50 mg twice daily with Methotrexate for rheumatoid arthritis for 12 weeks.
Arm Title
Placebo and Methotrexate
Arm Type
Placebo Comparator
Arm Description
Participants in this arm will receive Placebo with Methotrexate for rheumatoid arthritis for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Cilostazol
Intervention Description
Cilostazol 50 MG
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
change in DAS-28 CRP score
Description
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.
Time Frame
Baseline,12 weeks
Title
Change in Multi Dimensional Health Assessment score
Description
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.
Time Frame
Baseline,12weeks
Title
Change in Visual analog scale for pain
Description
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.
Time Frame
Baseline,12 weeks
Secondary Outcome Measure Information:
Title
Change in the serum level of the assessed biological marker C-reactive protein
Description
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.
Time Frame
Baseline,12weeks
Title
Change in the serum level of the assessed biological marker Nuclear factor kabba-B p65
Description
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.
Time Frame
Baseline,12weeks
Title
Change in the serum level of the assessed biological marker Hemeoxygenase-1
Description
Hemeoxygenase-1 .
Time Frame
Baseline,12weeks
Title
Change in the serum level of the assessed biological marker Cyclic adenosine monophosphate
Description
Cyclic adenosine monophosphate level.
Time Frame
Baseline,12weeks
Other Pre-specified Outcome Measures:
Title
Numbers of participants with treatment-related adverse events
Description
The adverse events in each group will be observed and documented during the whole procedure to show the safety of the treatment.
Time Frame
Baseline,12weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Samar Mahmoud Eldadamouny, Pharmacist
Phone
+201008456735
Email
samer.abdelfattah99@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Tarek Mohamed Mostafa, Professor
Phone
+201154594035
Email
tarek.mostafa@pharm.tanta.edu.eg
Facility Information:
Facility Name
Faculty of medicine
City
Mansoura
Country
Egypt
Individual Site Status
Recruiting
12. IPD Sharing Statement
Citations:
PubMed Identifier
22820172
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.
Results Reference
background
PubMed Identifier
26170060
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.
Results Reference
background
PubMed Identifier
17265482
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.
Results Reference
background
PubMed Identifier
20131233
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.
Results Reference
background
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Cilostazol and Methotrexate in Rheumatoid Arthritis
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