Hydroxychloroquine/Atorvastatin in the Treatment of Osteoarthritis (OA) of the Knee
Condition: Osteoarthritis of the Knee
MeSH terms: Osteoarthritis; Osteoarthritis, Knee
Intervention: Hydroxychloroquine/Atorvastatin
Intervention description: Hydroxychloroquine 200-600 mg /day Atorvastatin 40 mg/day
Intervention MeSH terms: Hydroxychloroquine; Atorvastatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: OA; Knee

Summary:

      The purpose of this study of a combination therapy of hydroxychloroquine and atorvastatin is
      to learn about the effects in inflammation and pain in patients with Osteoarthritis of the
      knee. These medications are FDA approved and commercially available.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Ambulatory subjects with OA of the knee with symptoms for at least 6 months and pain
             on the majority of days in the last 30 days. Symptoms must include knee joint pain.

          2. Male or female adults age >40 years with a body mass index <35

          3. Radiographic evidence of at least one osteophyte in either knee on posteroanterior
             (PA) and lateral standing, flexed x-ray.

          4. A Kellegren-Lawrence score of 2-3, or KL score of 1 accompanied by a clinically
             apparent effusion in the index knee.

          5. A WOMAC pain score of >8 on the index knee at screening visit.

        Exclusion Criteria:

          1. A requirement for treatment with high potency opioids for pain relief.

          2. Unwilling to abstain from NSAIDs and/or other analgesic medications except
             acetaminophen (i.e., COX-2 inhibitors, tramadol) for 48 hours and acetaminophen for 24
             hours prior to pain assessments during the study. Subjects taking low dose aspirin for
             cardiovascular health may remain on their stable dose throughout the study.

          3. On an unstable dose of NSAIDs or analgesics for at least 1 months prior to screening
             visit 1.

          4. Using a handicap assistance device (i.e., cane, walker) >50% of the time.

          5. Undergoing new physical therapy or participating in a weight loss or exercise program
             that has not been stable for at least 3 months prior to screening visit 1 and will not
             remain stable during their participation in the study.

          6. Had a previous history of arthroscopic or open surgery to the index knee in the past 6
             months or planned surgery during study follow up.

          7. Had joint replacement surgery in the index knee.

          8. Received corticosteroid, short acting hyaluronic acid, or other intraarticular
             injections of the index knee within 3 months of screening visit 1 and/or not willing
             to abstain from treatments for the duration of the study

          9. A history in the past 5-10 years of reactive arthritis, rheumatoid arthritis,
             psoriatic arthritis, ankylosing spondylitis, arthritis associated with inflammatory
             bowel disease, sarcoidosis, amyloidosis or fibromyalgia.

         10. Clinical signs and symptoms of active knee infection or radiographic evidence of
             crystal disease other than chondrocalcinosis (i.e. gout).

         11. A history of abnormal laboratory results >2.5 x ULN indicative of any significant
             medical disease, which in the opinion of the investigator, would preclude the subjects
             participation in the study

         12. Any of the following abnormal laboratory results during screening:

               -  ALT and/or AST >2.5x ULN

               -  Hemoglobin <9 g/dL

               -  WBC <3500 cells/mm3

               -  Lymphocyte count <1000 cells/mm3

               -  Serum creatinine >1.5 x ULN or calculated Glomerular filtration rate less than
                  50.

               -  Creatine phosphokinase level > 2x ULN

         13. A history of malignancy in the past ten years (<10 years), with the exception of
             resected basal cell carcinoma, squamous cell carcinoma of the skin, or resected
             cervical atypia or carcinoma in situ.

         14. Significant hip pain, ipsilateral to the index knee that may interfere with
             assessments of index knee pain

         15. A known or clinically suspected infection with human immunodeficiency virus (HIV), or
             hepatitis C or B viruses

         16. Participated within 3 months or will participate concurrently in another
             investigational drug or vaccine study

         17. A history of drug or alcohol dependence or abuse in the past 3 years

         18. A female with reproductive capability who is unwilling to use birth control for the
             duration of the study and/or intends to conceive within 12 months of dosing.

         19. Ongoing use of hydroxychloroquine, or any anti-malarial, or prior history of use
             within past 3 months or any prior history of history of allergy, hypersensitivity or
             toxicity to antimalarial use.

         20. Ongoing use of a statin (HMG Co A reductase inhibitor), or use within past 3 months or
             any prior history of history of allergy, hypersensitivity, or toxicity to statin use.

         21. Use of fibric acid derivative in past 3 months.

         22. Other serious, non-malignant, significant, acute or chronic medical or psychiatric
             illness that, in the judgment of the investigator, could compromise subject safety,
             limit the subject's ability to complete the study, and/or compromise the objectives of
             the study.-