The Phosphodiesterase 3 Inhibitor Cilostazol as an Adjunct to Conventional Therapy in Patients With Osteoarthritis

Study Overview
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Brief Summary
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Cilostazol is able to suppress the degradation of type II collagen in human chondrocytes induced by IL-1b. Cilostazol add-on for celecoxib therapy has synergistic anti-arthritic potential by inhibiting proinflammatory cytokine production in synovial fibroblasts through the IL-10/SOCS3 pathways, consequently leading to the inhibition of synovial cell proliferation and overcoming the perpetuation of synovial inflammation.

Official Title
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The Phosphodiesterase 3 Inhibitor Cilostazol as an Adjunct to Conventional Therapy in Patients With Osteoarthritis: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial

Conditions
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Osteoarthritis

Intervention / Treatment
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* Drug: Cilostazol 50 MG
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary osteoarthritis Patients recruited were between 30 to 60 years of age, with X-ray confirmed Kellgren-Lawrence grade13 II or III severity primary tibiofemoral OA, according to the American College of Rheumatology criteria. Exclusion Criteria: Those patients were excluded from the present study who: were of age less than 30 years or more than 60 years presented with active concomitant gastroduodenal disorders, hepatic and renal impairment within last 30 days prior to receiving the study drug were diagnosed to have any inflammatory arthritis, gout or acute trauma of the knee, hip or spine; accompanying OA of the hip of sufficient severity to interfere with the functional assessment of the knee had previous or ongoing treatment with oral SYSDOA (e.g., glucosamine sulphate, chondroitin sulphate, diacerein, piascledine), anti-depressants, tranquillisers, antacids or antibiotics; were having active cardiac lesion or hypertension, were pregnant females and those who were planning their pregnancy during the study were having a known hypersensitivity to the used medications have persistent diarrhoea or laxative use; severe gastrointestinal disorders, severe obesity, severe parenchymal organ disease, or anaemia (haemoglobin< 10.0 g/ dl or haematocrit < 30%). Patients who received oral, intramuscular, intraarticular or soft tissue injections of corticosteroids within last eight weeks before receiving the first dose of the study medication, or had undergone joint lavage and arthroscopic procedures in the previous 6 months, were also excluded.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cilostazol<br>Cilostazol 50 mg twice daily plus Celecoxib 200mg capsule | Drug: Cilostazol 50 MG<br>* Cilostazol 50 mg twice daily plus Celecoxib 200mg capsule<br>|
| Placebo Comparator: Placebo<br>Placebo tablet twice daily plus Celecoxib 200mg capsule | Drug: Placebo<br>* Placebo tablet twice daily plus Celecoxib 200mg capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analogue scale assessment of pain | the change of Visual Analogue Scale (VAS) pain score from baseline to posttreatment. Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between no pain and worst pain. | week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WOMAC change | the change of WOMAC Osteoarthritis Index from baseline to posttreatment | week 12 | 
| the change of Short Form 36 Questionnaire (SF-36) score from baseline to posttreatment | The SF-36 is a generic instrument to assess health-related quality of life. It consists of 36 questions and assesses 8 dimensions: physical functioning, role physical, pain index, general health, vitality, social functioning, role emotional, and mental health index. It also provides 2 summary measures of physical and mental components. The SF-36 score ranges from 0 to 100, with higher scores indicating better health status. | week 12 | 
| Adverse drug reaction | Clinical side effects | 12 weeks | 
| Interleukin 1 beta | Interleukin 1 beta serum level | 12 weeks | 
| Serum level Tumor necrosis factor- alpha (TNF-α) | Serum level Tumor necrosis factor- alpha (TNF-α) | 12 weeks | 
| Serum levels of IL-17 | Serum levels of IL-17 | 12 weeks | 
| Serum levels of BDNF | Serum levels of BDNF | 12 weeks | 
| Serum levels of IL-10 | Serum levels of IL-10 | 12 WEEKS |