Trial of Naproxen to Evaluate Various Methods of Measuring Analgesic Effect in Osteoarthritis Pain of the Knee

Study Overview
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Brief Summary
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This study aims to evaluate various methods of measuring pain relief in subjects who have chronic OA of the knee. After a 1 week of wash-out from existing therapy, subjects will be treated in a blinded fashion for 1 week with either naproxen (3 days at 250 mg twice a day followed by 4 days at 500 mg twice a day) or placebo. After the first week of treatment, subjects will have another week of wash-out followed by a second period of 1 week of the alternate treatment. Subjects will not be allowed to use oral non-steroidal anti-inflammatory drugs (NSAIDs) or other oral analgesics, or topical medications on their target knees during the study. Acetaminophen will be allowed as a rescue medication.

Detailed Description
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This study aims to evaluate various methods of measuring pain relief in osteoarthritis (OA) of the knee. The duration of the study will be up to 5 weeks. Eligible subjects will have chronic OA of the knee. After meeting initial entry criteria and prior to randomization, there will be a 1 week wash-out from existing therapy. Subjects will then be treated in a blinded fashion for 1 week with either naproxen (3 days at 250 mg twice a day followed by 4 days at 500 mg twice a day) or placebo. After the first week of treatment, subjects will have a week of wash-out followed by a second period of 1 week of the alternate treatment. Subjects will not be allowed to use oral non-steroidal anti-inflammatory drugs (NSAIDs) or other oral analgesics, nor will they be allowed to use topical medications on their target knees during the study. Acetaminophen will be allowed as a rescue medication (as needed up to 2 g/day)but subjects will be told not to take acetaminophen at least 12 hours before study visits. Seventy (70) subjects will be randomized to ensure that 60 subjects complete both treatment arms.

Official Title
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A Randomized, Double-Blind, Placebo-controlled Cross-over, Exploratory Trial of Naproxen to Evaluate Methods of Measuring Analgesic Effect in Osteoarthritis Pain of the Knee

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Drug: Naproxen
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject able to read, comprehend and sign written Informed Consent Form Subject is 21 years old or older If female, should be post-menopausal or has negative urine test Subject has some degree of target joint pain for the last 3 months Subject has to have 3 out of six: ( )Age > 50 ( )Morning stiffness < 30 minutes ( )Crepitus on active motion ( )Bony enlargement ( )No palpable warmth of synovium Subject had an X-ray of the target knee showing evidence of OA within the past 3 years Target joint does not contain any type of orthopedic and/or prosthetic device Subject is ambulatory Subject is in good general medical and psychological health, and is capable of completing study assessments and procedures. Exclusion Criteria: Subject had an x-ray of the target knee showing Kellgren-Lawrence grade 4 Subject has any pain syndrome that has the potential to confound the assessment of the target knee. the subject has a documented history of an adverse reaction to NSAIDs or acetaminophen Subject is pregnant or breast feeding Subject has sitting systolic pressure > 180 mmHg or < 90mmHg, and/or a sitting diastolic pressure > 100 mmHg or < 50 mmHg at screening Subject has mass body index (BMI) > 35 kg/m2. Subject has a Hospital Anxiety and Depression Scale (HADS) score > 12 on either subscale or has an established history of major depressive disorder not controlled with medication Subject has had an introduction of physiotherapy, acupuncture, or transcutaneous electrical nerve stimulation within 4 weeks before screening, or has no stable regimen of these modalities. Subject has a clinically significant abnormalities in clinical chemistry, hematology, coagulation, or urinalysis. Subject has a significant history or renal impairment Subject has a positive urine drug screen for alcohol, illicit drugs or nonprescribed controlled substances Subject has dermatological lesions of the target knee or ipsilateral elbow at the time of screening. Subject is unable to discontinue all formulations of prior analgesics Subject has received any investigational drug within 30 days prior to screening Subject has a history of active peptic ulceration, gastrointestinal bleeding, esophageal, or gastric or duodenal ulcer within 3 months of screening Subject has had a surgical intervention for any pain within 3 months of screening or plans for surgical intervention while in the study Subject has a documented history of inflammatory arthritis, including rheumatoid arthritis. Subject has received local corticosteroid injections, viscosupplementation, or arthrocentesis in the target joint within 3 months of screening Subject has received oral or intramuscular corticosteroids within the past 30 days Subject is involved in an ongoing or settled worker's compensation claim, disability, or litigation related to any pain problem Subject had used opioids for pain more than 4 days in the week preceding screening Subject has a history of alcohol or drug abuse/dependence/misuse within 2 years of screening Subject has history of acute coronary syndrome, ischemic or hemorrhagic stroke, transient ischemic attack, or previous revascularization procedure to coronary or peripheral vasculature, or has a history of congestive heart failure within 5 years of screening Subject has had axillary lymph nodes removed bilaterally Subject has a disease-related or iatrogenic coagulopathy, or had been diagnosed with thrombocytopenia or a functional platelet disorder The subject is currently on an aromatase inhibitor. Subject has a history of any condition that, in the Investigator's opinion, precludes participation in the study

Ages Eligible for Study
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Minimum Age: 21 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Naproxen<br> | Drug: Naproxen<br>* Naproxen for 7 days (3 days at 250 mg BID followed by 4 days at 500 mg BID) during either of the 2 treatment periods.<br>* Other names: Naprosyn;Drug: Placebo<br>* Placebo for seven days given BID during either of the 2 treatment periods.<br>* Other names: Sugar pill;|
| Sham Comparator: Placebo<br> | Drug: Naproxen<br>* Naproxen for 7 days (3 days at 250 mg BID followed by 4 days at 500 mg BID) during either of the 2 treatment periods.<br>* Other names: Naprosyn;Drug: Placebo<br>* Placebo for seven days given BID during either of the 2 treatment periods.<br>* Other names: Sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of naproxen vs. placebo | Efficacy of naproxen VS placebo will be analyzed by efficacy end-points of within-subject difference. Efficacy evaluations will include: In-clinic pain intensity NRS (24-hour recall) WOMAC: pain subscale, stiffness subscale, function subscale, and total scores Daily actiwatch pain intensity In-clinic pain intensity NRS for curent pain at rest and after exercise Thermal pain matching at rest and after exercise PGIC (Patient's Global Impression of Change) Subject treatment reference | 5 weeks | 
| Safety | Safety of Naproxen VS Placebo Safety evaluations will include: Adverse events (AEs)and serious AEs (SAEs) Vital signs Clinical Laboratories Concomitant medications | 5 weeks | 

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