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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Osteoarthritis
• Intervention / Treatment: Drug: Cilostazol 50 MG; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Egypt
  • Menoufia
    • Shibīn Al Kawm, Menoufia, Egypt, 13829
      • Faculty of Pharmacy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cilostazol; Cilostazol 50 mg twice daily plus Celecoxib 200mg capsule	Drug: Cilostazol 50 MG; Cilostazol 50 mg twice daily plus Celecoxib 200mg capsule
Placebo Comparator: Placebo; Placebo tablet twice daily plus Celecoxib 200mg capsule	Drug: Placebo; Placebo tablet twice daily plus Celecoxib 200mg capsule

What is the study measuring?

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
Serum level Tumor necrosis factor- alpha (TNF-α)	Serum level Tumor necrosis factor- alpha (TNF-α)	12 weeks
Interleukin 1 beta	Interleukin 1 beta serum level	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

Collaborators and Investigators

• Sponsor: Sadat City University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Estimated): December 30, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: March 6, 2021
• First Submitted That Met QC Criteria: March 6, 2021
• First Posted (Actual): March 10, 2021

Study Record Updates

• Last Update Posted (Estimated): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Neuroprotective Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Cilostazol
• Other Study ID Numbers: 15/2021RHU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No