Flavocoxid, A Plant-Derived Therapy, for the Treatment of Knee Osteoarthritis

The University of Alabama at Birmingham

Status and phase

Completed

Phase 1

Conditions

Osteoarthritis

Treatments

Drug: Flavocoxid

Drug: Placebo

Study type

Interventional

Funder types

Other

Industry

NIH

Identifiers

NCT00294125

R41AR051232 (U.S. NIH Grant/Contract)

1R41AR051232-01A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed to treat arthritis. The purpose of this study is to test the effectiveness of flavocoxid, a plant-derived compound, for the treatment of knee osteoarthritis (OA) in adults.

Study hypotheses: 1) Flavocoxid has an acceptable safety and tolerability profile as determined by the Generally Regarded as Safe (GRAS) profile in patients with OA compared to identical placebo. 2) Flavocoxid will be more effective as a therapy for OA compared to identical placebo.

Full description

OA is a leading chronic disease in older adults and is characterized by degeneration of articular cartilage of the joints in hands, spine, knees, and hips. In joints, tissue injury and pain are caused by the conversion of arachidonic acid to such inflammatory compounds as cyclooxygenases-1 and -2 (COX-1 and -2) and 5-lipoxygenase (5-LO). Conventional NSAIDs inhibit COX-1 and -2, but have little or no effect on 5-LO. NSAIDs provide relief from the pain of OA; however, NSAIDS are also associated with significant side effects, including gastrointestinal bleeding, venous thrombosis, and nephrotoxicity. Novel alternative therapies with increased safety and efficacy with fewer or no side effects are desirable; plant-derived substances might be useful alternatives to NSAIDs. Flavocoxid, a botanical extract derived from two plants, Scutellaria baicalensis and Acacia catechu, has been shown to inhibit COX-1 and -2 as well as 5-LO. The purpose of this study is to evaluate the safety and efficacy of flavocoxid in relieving the symptoms of knee OA in adults.

This study will last 12 weeks. Participants will be randomly assigned to one of two groups. Group 1 participants will receive daily flavocoxid; Group 2 participants will receive placebo. There will be 5 study visits: study entry and Weeks 2, 4, 8, and 12. Joint pain, tenderness, and swelling will be assessed at each study visit. A 30-foot timed walking test will also be performed at all visits. A physical exam and blood collection will occur at study entry and Week 12. Other study assessments will include safety monitoring, patient/physician global disease ratings, quality of life measures, depression and anxiety ratings, and measures of efficacy as determined by the Western Ontario and McMaster (WOMAC) OA index.

Enrollment

59 patients

Sex

All

Ages

40 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Meet American College of Rheumatology (ACR) clinical criteria for knee OA
In good medical and psychological health
Able and willing to discontinue NSAIDs, natural therapies, and other pain medications for OA for 1 week prior to the first study visit and also throughout the course of the clinical trial
Knee pain rated greater than 4 cm on a 10 cm visual analog scale (VAS)
Intends to stay in the area and complete the 12-week protocol
Willing to use acceptable forms of contraception

Exclusion criteria

Serious or unstable concomitant medical or psychological illnesses that would impair the patient's ability to complete the study
Significant cardiac disease OR history of myocardial infarction in the 12 months prior to study entry
Uncontrolled hypertension
Significant bleeding disorders. Participants who have bleeding disorders related to uncontrolled, bleeding hemorrhoids occurring in the 12 months prior to study entry are not excluded.
Uncontrolled gastrointestinal disease resulting in bleeding in the 60 days prior to study entry. Participants with controlled and uncomplicated ulcers are not excluded.
Inflammatory arthritis, gout, pseudogout, Paget's disease, or any chronic pain syndrome
Severe pes anserine bursitis, acute joint trauma, or complete loss of articular cartilage on the index knee
Intravenous, intramuscular, or intra-articular steroids to the index joint within 60 days of study screening
Alcohol, intravenous drug, or prescription drug abuse
Investigational drugs within 30 days of study screening
Current use of anticoagulants such as warfarin
Oral corticosteroids or other immunosuppressants within 6 months of study screening
Severe psoriasis requiring use of biologic immunomodulators such as alefacept, etanercept, infliximab, or cyclosporine
Hypersensitivity to analgesics, cyclo-oxygenase inhibitors, lipoxygenase inhibitors, or flavonoids
Pregnancy or breastfeeding

Exclusion Criteria Postenrollment:

Abnormal laboratory test results at study screening, as determined by the investigator
Liver enzyme levels (SGOT, SGPT, alkaline phsphatase) two times the upper limit of normal
Leukocyte counts less than 3.5 times 109/L or platelet counts less than 150 times 109/L
At increased risk for cardiovascular problems based on the Framingham Cardiac Risk assessment questionnaire
Kellgren/Lawrence radiographic score of 0, 1, or 4 on x-ray of index joint taken within 12 months of study entry
Impaired renal function (creatinine greater than 1.5 mg/dl)