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

Study Overview
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Brief Summary
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This is a pilot study with a 4-period double-cross-over design evaluating a treatment with non-steroidal anti-inflammatory drugs (NSAIDs) in people with painful knee osteoarthritis.

Detailed Description
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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.

Official Title
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N of 1 Pilot Study of Nonsteroidal Anti-inflammatory Drugs in People With Painful Knee Osteoarthritis

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Drug: Naproxen 500 Mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Participants will be entered into the trial and have 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 and the treatment allocation and IP will be blinded.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cross-over Treatment: Initial treatment with naproxen<br>There will be a 4 period cross-over: 2 weeks of treatment with IP, followed by 2 weeks of washout, and this repeated 3 more times. Treatment will be such that all participants will receive 2 treatment periods with naproxen and 2 treatment periods with placebo. The order of treatment will be randomized and the treatment allocation and IP will be blinded. | Drug: Naproxen 500 Mg<br>* naproxen tablets<br>* Other names: non steroidal anti inflammatory drugs (NSAID);Drug: Placebo<br>* lactose NF<br>|
| Experimental: Cross-over Treatment: Initial treatment with placebo<br>There will be a 4 period cross-over: 2 weeks of treatment with IP, followed by 2 weeks of washout, and this repeated 3 more times. Treatment will be such that all participants will receive 2 treatment periods with naproxen and 2 treatment periods with placebo. The order of treatment will be randomized and the treatment allocation and IP will be blinded. | Drug: Naproxen 500 Mg<br>* naproxen tablets<br>* Other names: non steroidal anti inflammatory drugs (NSAID);Drug: Placebo<br>* lactose NF<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean of one week's daily pain ratings on Numeric Pain Scale (NRS) 0-10; higher worse | daily pain will be collected by a web application and averaged over a 7day period; higher scores imply more pain | baseline to end of 14 day treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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osteoarthritis, responder