Study of Nonsteroidal Anti-inflammatory Drugs in People With Painful Knee Osteoarthritis

Once screened and found eligible, participants will be entered into an initial blinded 2-week treatment period of either naproxen or placebo and then entered into an open washout period of 2 weeks. At the end of this washout, participants will then receive either naproxen or placebo for a further 2 week period followed again by a 2 week washout. This sequence will then be repeated (total of 4 treatment periods) such that all participants receive naproxen for 2 treatment periods and placebo for 2 treatment periods. The order of treatment will be randomized.

Inclusion criteria

• Male or female >40 years of age
• Meet ACR criteria for knee OA
• Able and willing to provide informed consent
• Average weekly pain in the index knee based on daily pain assessments of ≥ 4/10 and <9/10 on an 11-point NRS scale
• Willing to discontinue current medications taken for OA pain
• For women of child-bearing potential, willing to utilize some form of birth control or abstinence during the course of the study
• If taking cannabinoids, have to be on a stable dose and have this maintained for the duration of the study
• If receiving physical therapy or any non-pharmacologic modality(ies) for OA, these need to continue and remain stable for the duration of the study
• Ambulatory
• Have a cellphone and/or access to a computer and be able to utilize the eDiary as directed
• Use of medications for knee OA pain on at least 4 out of 7 days per week
• eDiary entries on at least 4 out 7 days per week during the observation period
• Sub-Group Criterion (≥12 participants): Variability of average daily pain in the index knee during the observation period of ≥ 2 points on the NRS scale on at least 4 occasions

Exclusion criteria

• History of intolerance or allergic reaction to NSAIDs
• Previous history of GI bleed
• Renal insufficiency resulting in serum creatinine > 1.5 mg/dL
• History of myocardial infarction in last 6 months
• Coexisting congestive heart failure or symptomatic atherosclerotic heart disease
• Use of oral anticoagulants other than aspirin ≤ 325 mg for cardiac prophylaxis
• Use of heparin or injectable anticoagulant
• Uncontrolled hypertension
• Any medical condition which in the judgement of the investigator would make it inappropriate for the participant to enroll in the study
• Use of recreational drugs
• Fibromyalgia
• Inflammatory arthropathies of any sort
• Chronic back pain in which pain level is greater than the OA pain
• Participation in another clinical trial other than one for covid or an observational and non-interventional study
• Use of walker or other aid for walking other than a single cane
• Hip pain on the ipsilateral side equal to or greater than the knee pain in the index joint
• Index knee cannot have had previous joint replacement surgery
• Arthroscopy within the past 6 months
• Injection of hyaluronate in the index knee in the past 6 months
• Corticosteroid injection in the index knee in the past 3 months
• Injection of any biologic agent in the index in the past 12 months
• Nerve ablation for the treatment of pain in the index knee
• Any acute or chronic pain condition which would interfere with the evaluation of knee pain.
• Pregnant, nursing or planning to become pregnant during length of study