Back to resultsThe Effect of Cilostazol on Rheumatoid Arthritis Patients
Primary Purpose
Rheumatoid Arthritis
Status
Recruiting
Phase
Phase 2
Locations
Egypt
Study Type
Interventional
Intervention
Cilostazol 100 MG
conventional synthetic antirheumatic drugs
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid Arthritis, Cilostazol
Eligibility Criteria
Inclusion Criteria: Adult patients. (>18 years old). Moderate to high disease activity (DAS28-CRP>3.2). Patients receiving stable cDMARD regimen for at least 3 months before inclusion in the study. Exclusion Criteria: Hypersensitivity to cilostazol. Heart failure. Pregnant and lactating women. Patients with liver impairment (ALT or AST > 3* ULN). Patients with renal impairment (CrCl<60 mL/min). Patients receiving any other antiplatelet or anticoagulant
Sites / Locations
- Al-Zahraa HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Cilostazol arm
Control
Arm Description
35 patients receiving conventional synthetic disease modifying antirheumatic drugs in addition to Cilostazol 100 mg twice daily for 6 months.
35 patients receiving conventional synthetic disease modifying antirheumatic drugs for 6 months.
Outcomes
Primary Outcome Measures
Change in the DAS-28 CRP score
DAS-28 score is used to asses disease severity in Rheumatoid Arthritis. It incorporates the swollen and tender joints present in 28 joints together with the c-reactive protein measurement into an equation to calculate the disease severity.
0.56*
√(TJC28) + 0.28* √(SJC28) + 0.36*ln (CRP + 1) +0.014*(GH) + 0.96
where TJC:is tender joint count SJC is : swollen joint count GH:patient assessment of disease activity using a 100 mm visual analogue scale (VAS) with 0 = best, 100 = worst
a number is given which is equal to a specific disease severity.
website to calculate the DAS-28 score : https://www.4s-dawn.com/DAS28/
Secondary Outcome Measures
Health Assessment Questionnaire
Rheumatoid arthritis health assessment questionnaire is a self-administered questionnaire help assess patients' functional status. Health assessment questionnaire is validated and present in Arabic language to be administered to Egyptian patients.
There are 8 categories in the HAQ assessing the daily activities. In each category the highest score is taken. There are 2 to 3 questions in each category with a scale from 0 to 3 where 0 means no functional limitation and 3 means unable to do this activity. If the patient is using an assistive device the minimum score for this category should be 2. At the end the patient category score is added and divided by 8. The final score is given from 0 to 3 where 3 indicates a poor quality of life.
Total antioxidant capacity (TAC)
Oxidative stress is linked to the pathogenesis of various diseases including RA, cilostazol was shown to decrease the oxidative stress in other disease. so measuring the total antioxidant capacity in order to show the oxidative stress levels.
Malondialdehyde (MDA)
Malondialdehyde is a reactive oxygen species molecule. the level of MDA reflect the oxidative stress present which is important for the pathogenesis of various diseases including Rheumatoid arthritis
TNF α
TNF-alpha is a pro-inflammatory marker used to detect degree of inflammation , and as Rheumatoid arthritis is an inflammatory disease , TNF-alpha measurement would give an insight to RA inflammatory state. TNF-alpha is
phosphorylated Adenosine monophosphate-activated protein kinase (p-AMPK)
p-AMPK is an important marker of inflammatory response as it inhibits inflammatory pathway, measuring p-AMPK would give an insight on the inflammatory response present in Rheumatoid arthritis
Vascular cell adhesion protein 1(VCAM-1)
ilostazol was reported to improve the endothelial dysfunction associated with diabetes in diabetic rats through decreasing the adhesion molecules, such as VCAM-1 by an AMPK dependent action which could be beneficial in RA associated endothelial dysfunction
Cilostazol safety
Cilostazol safety will be monitored by asking patients through monthly visits and using phone calls every 2 weeks about occurrence of any side effects. The expected side effects of cilostazol are; headache, diarrhea and nausea and stomach pain. Some serious side effects can occur such as bruising , bleeding , palpations and swelling of the arms, hands, feet, ankles, or lower legs
Full Information
NCT ID
NCT05671497
First Posted
December 14, 2022
Last Updated
December 26, 2022
Sponsor
Ain Shams University
Collaborators
Misr International University, Al-Azhar University
1. Study Identification
Unique Protocol Identification Number
NCT05671497
Brief Title
The Effect of Cilostazol on Rheumatoid Arthritis Patients
Official Title
Evaluation of the Effect of Cilostazol on the Clinical Outcomes of Rheumatoid Arthritis Patients
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 1, 2022 (Actual)
Primary Completion Date
October 1, 2023 (Anticipated)
Study Completion Date
October 1, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ain Shams University
Collaborators
Misr International University, Al-Azhar University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The goal of this study is to evaluate the effect of cilostazol on Rheumatoid Arthritis patients. It aims to answer the questions of :
Will Cilostazol improve the disease severity and quality of life in Rheumatoid arthritis patients?
Will Cilostazol decrease the oxidative stress, inflammation and endothelial dysfunction in Rheumatoid arthritis patients?
Participants will be randomized into two arms either treatment or control the treatment group will be asked to take Cilostazol 100 mg twice daily in addition to the usual DMARD (Methotrexate , Sulfasalazine , Hydroxychloroquine or Leflunomide), while the control group will be taking the usual DMARDs only.
Patients in both arms will be followed-up every 2 weeks through out the 6-month duration of the study.
Detailed Description
Rheumatoid Arthritis (RA) is an autoimmune disease affecting joints. It usually affects females more. The available treatment aims to slow down disease progression and control the disease symptoms. Treatment is classified into either the conventional DMARDs (Methotrexate , Sulfasalazine , Hydroxychloroquine or Leflunomide) or Biological DMARDs such as an Anti-TNF alpha ( Certolizumab, Infliximab , Etanercept or Golimumab) or non-TNF biologics (Rituximab, Abatacept or Tocilizumab). Both classes have their drawbacks. The conventional DMARDs is not effective for many patients and the biological DMARDs have a high cost making their use limited to patients with medical insurance or patients who can afford it, thus making it necessary to find new medications which can improve the outcomes in patients with RA.
Cilostazol is an antiplatelet agent used mainly for intermittent Claudication. Recently many preclinical trials have shown efficacy of cilostazol in RA via it's anti-inflammatory action. it also decreases the oxidative stress which is high in ٌRA patients.
Patients will be randomized into two arms , one which is treatment and the other is control the treatment group will be asked to take Cilostazol 100 mg twice daily in addition to the usual DMARD (Methotrexate , Sulfasalazine , Hydroxychloroquine or Leflunomide), while the control group will be taking the usual DMARDs only.
Patients in both arms will be followed-up every 2 weeks through out the 6-month duration of the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Rheumatoid Arthritis, Cilostazol
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
70 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cilostazol arm
Arm Type
Experimental
Arm Description
35 patients receiving conventional synthetic disease modifying antirheumatic drugs in addition to Cilostazol 100 mg twice daily for 6 months.
Arm Title
Control
Arm Type
Active Comparator
Arm Description
35 patients receiving conventional synthetic disease modifying antirheumatic drugs for 6 months.
Intervention Type
Drug
Intervention Name(s)
Cilostazol 100 MG
Intervention Description
An antiplatelet agent used for intermittent claudication , it has an anti-inflammatory effect which will help control patients with Rheumatoid arthritis
Intervention Type
Drug
Intervention Name(s)
conventional synthetic antirheumatic drugs
Intervention Description
methotrexate 7.5-15 mg once weekly hydroxychloroquine 200 mg twice daily sulfasalazine 500 mg to 3 g once daily leflunomide 20 mg once daily
Primary Outcome Measure Information:
Title
Change in the DAS-28 CRP score
Description
DAS-28 score is used to asses disease severity in Rheumatoid Arthritis. It incorporates the swollen and tender joints present in 28 joints together with the c-reactive protein measurement into an equation to calculate the disease severity.
0.56*
√(TJC28) + 0.28* √(SJC28) + 0.36*ln (CRP + 1) +0.014*(GH) + 0.96
where TJC:is tender joint count SJC is : swollen joint count GH:patient assessment of disease activity using a 100 mm visual analogue scale (VAS) with 0 = best, 100 = worst
a number is given which is equal to a specific disease severity.
website to calculate the DAS-28 score : https://www.4s-dawn.com/DAS28/
Time Frame
Baseline, after 3 months , After 6 months
Secondary Outcome Measure Information:
Title
Health Assessment Questionnaire
Description
Rheumatoid arthritis health assessment questionnaire is a self-administered questionnaire help assess patients' functional status. Health assessment questionnaire is validated and present in Arabic language to be administered to Egyptian patients.
There are 8 categories in the HAQ assessing the daily activities. In each category the highest score is taken. There are 2 to 3 questions in each category with a scale from 0 to 3 where 0 means no functional limitation and 3 means unable to do this activity. If the patient is using an assistive device the minimum score for this category should be 2. At the end the patient category score is added and divided by 8. The final score is given from 0 to 3 where 3 indicates a poor quality of life.
Time Frame
Baseline, after 3 months , After 6 months
Title
Total antioxidant capacity (TAC)
Description
Oxidative stress is linked to the pathogenesis of various diseases including RA, cilostazol was shown to decrease the oxidative stress in other disease. so measuring the total antioxidant capacity in order to show the oxidative stress levels.
Time Frame
Baseline and at 6 months
Title
Malondialdehyde (MDA)
Description
Malondialdehyde is a reactive oxygen species molecule. the level of MDA reflect the oxidative stress present which is important for the pathogenesis of various diseases including Rheumatoid arthritis
Time Frame
Baseline and at 6 months
Title
TNF α
Description
TNF-alpha is a pro-inflammatory marker used to detect degree of inflammation , and as Rheumatoid arthritis is an inflammatory disease , TNF-alpha measurement would give an insight to RA inflammatory state. TNF-alpha is
Time Frame
Baseline and at 6 months
Title
phosphorylated Adenosine monophosphate-activated protein kinase (p-AMPK)
Description
p-AMPK is an important marker of inflammatory response as it inhibits inflammatory pathway, measuring p-AMPK would give an insight on the inflammatory response present in Rheumatoid arthritis
Time Frame
Baseline and at 6 months
Title
Vascular cell adhesion protein 1(VCAM-1)
Description
ilostazol was reported to improve the endothelial dysfunction associated with diabetes in diabetic rats through decreasing the adhesion molecules, such as VCAM-1 by an AMPK dependent action which could be beneficial in RA associated endothelial dysfunction
Time Frame
baseline and at 6 months
Title
Cilostazol safety
Description
Cilostazol safety will be monitored by asking patients through monthly visits and using phone calls every 2 weeks about occurrence of any side effects. The expected side effects of cilostazol are; headache, diarrhea and nausea and stomach pain. Some serious side effects can occur such as bruising , bleeding , palpations and swelling of the arms, hands, feet, ankles, or lower legs
Time Frame
From date of randomization then every two weeks up to 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult patients. (>18 years old).
Moderate to high disease activity (DAS28-CRP>3.2).
Patients receiving stable cDMARD regimen for at least 3 months before inclusion in the study.
Exclusion Criteria:
Hypersensitivity to cilostazol.
Heart failure.
Pregnant and lactating women.
Patients with liver impairment (ALT or AST > 3* ULN).
Patients with renal impairment (CrCl<60 mL/min).
Patients receiving any other antiplatelet or anticoagulant
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Omar Eltoukhy, Teaching Assistant
Phone
+201110666586
Email
omar.ashraf20@pharma.asu.edu.eg
Facility Information:
Facility Name
Al-Zahraa Hospital
City
Cairo
Country
Egypt
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hend Maghraby, Associate Professor
Phone
+201114911897
12. IPD Sharing Statement
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The Effect of Cilostazol on Rheumatoid Arthritis Patients
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