Rheumatoid ArthritisPhase 3NCT05594680
Cilostazol and Methotrexate in Rheumatoid Arthritis
A Phase 3 study testing Cilostazol and Methotrexate in people with Rheumatoid Arthritis, run by Tanta University at 1 site in Egypt.
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). Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Cilostazol and Methotrexate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Oct 2022to 1 Nov 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- Patients with hypersensitivity to study medications.
- Patients using antioxidants .
- Pregnant and lactating females.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Phosphodiesterase 3 Inhibitor Cilostazol as Adjunct to Methotrexate in Patients With Rheumatoid Arthritis
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).
Read the 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.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Cilostazol, Methotrexate, Placebo
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CilostazolDrug
Cilostazol 50 MG
MethotrexateDrug
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.
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Cilostazol and Methotrexate | Active comparator | Participants in this arm will receive Cilostazol 50 mg twice daily with Methotrexate for rheumatoid arthritis for 12 weeks. Receives: Drug: Cilostazol; Drug: Methotrexate |
| Placebo and Methotrexate | Placebo comparator | Participants in this arm will receive Placebo with Methotrexate for rheumatoid arthritis for 12 weeks. Receives: Drug: Methotrexate; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Baseline,12 weeks
Secondary outcomes (4)
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.
Measured: Baseline,12weeks
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.
Measured: Baseline,12weeks
Change in the serum level of the assessed biological marker Hemeoxygenase-1
Hemeoxygenase-1 .
Measured: Baseline,12weeks
Change in the serum level of the assessed biological marker Cyclic adenosine monophosphate
Cyclic adenosine monophosphate level.
Measured: Baseline,12weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2022
- Study start1 Oct 2022
- Primary completion1 Nov 2024 (estimated)
- Study completion1 Nov 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Tanta UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tanta University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Samar Mohammed Mahmoud Eldadamouny, Tanta University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05594680
- Sponsor's protocol ID
- cilostazol in rheumatoid
- Status last verified
- Apr 2024
- First submitted
- 18 Oct 2022
- Last updated
- 10 Apr 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 22820172Park 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.
PubMed 26170060Kirino 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.
PubMed 17265482Park 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.
PubMed 20131233Eldadamony 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.
PubMed 40380042
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Phosphodiesterase 3 Inhibitor Cilostazol as Adjunct to Methotrexate in Patients With Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT05594680
- Acronym / sponsor ID
- cilostazol in rheumatoid
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Tanta UniversityUniversity, hospital or other
- Study start
- 1 Oct 2022 (actual)
- Primary completion
- 1 Nov 2024 (estimated)
- Study completion
- 1 Nov 2024 (estimated)
- First posted
- 26 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cilostazol and Methotrexate | Active comparator | Drug: Cilostazol, Drug: MethotrexateParticipants in this arm will receive Cilostazol 50 mg twice daily with Methotrexate for rheumatoid arthritis for 12 weeks. |
| Placebo and Methotrexate | Placebo comparator | Drug: Methotrexate, Drug: PlaceboParticipants in this arm will receive Placebo with Methotrexate for rheumatoid arthritis for 12 weeks. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CilostazolCilostazol 50 MG | Drug | Cilostazol and Methotrexate |
| MethotrexateMethotrexate (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. | Drug | Cilostazol and Methotrexate, Placebo and Methotrexate |
| PlaceboPlacebo | Drug | Placebo and Methotrexate |
Primary outcome
change in DAS-28 CRP score
Time frame: Baseline,12 weeks
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
Time frame: Baseline,12weeks
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
Time frame: Baseline,12 weeks
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.
4 secondary outcomes
Change in the serum level of the assessed biological marker C-reactive protein
Time frame: Baseline,12weeks
Change in the serum level of the assessed biological marker Nuclear factor kabba-B p65
Time frame: Baseline,12weeks
Change in the serum level of the assessed biological marker Hemeoxygenase-1
Time frame: Baseline,12weeks
Change in the serum level of the assessed biological marker Cyclic adenosine monophosphate
Time frame: Baseline,12weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2024.
- Background: PubMed 22820172Kim 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.
- Background: PubMed 26170060Park 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.
- Background: PubMed 17265482Kirino 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.
- Background: PubMed 20131233Park 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.
- Derived from this study: PubMed 40380042Eldadamony 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cilostazol and Methotrexate in people with Rheumatoid Arthritis, run by Tanta University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Samar Mahmoud Eldadamouny, Pharmacist (+201008456735, samer.abdelfattah99@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
change in DAS-28 CRP score (time frame: Baseline,12 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05594680, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2024.