Background & Objectives: This study aimed to compare the clinical efficacy of two-drug regimen of glucosamine and chloroquine with one-drug regimen of glucosamine in treatment of knee osteoarthritis.

  Methods: In this randomized clinical trial, 30 patients received glucosamine and chloroquine (trial group) and 25 cases underwent treatment by only glucosamine (control group) for 12 weeks. To evaluate pain and disability, WOMAC ( Western Ontario and McMaster Universities) was used.

  Results: Mean value of WOMAC index in the trial group was 3.51 at the beginning, 1.96 in week 6, and 1.84 in week 12. In the control group, this value was 3.15 at the beginning, 2.36 in week 6, and 2.35 in week 12. In week 12, mean value of WOMAC index was significantly lower in the trial group compared to the control group (P = 0.02). In females aged less than 65 years and with body mass index of equal or less than 30, a significant difference regarding mean value of WOMAC index was seen in week 12 between two groups (P < 0.05).

  Conclusion: Two-drug regimen of glucosamine and chloroquine in a 12-week period had a better clinical efficacy than one-drug regimen of glucosamine in lowering the pain and improving joint function of patients with knee osteoarthritis, especially in females with body mass index less than 30 and younger than 65 years of age.