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

March 19, 2026 updated by: Thomas J. Schnitzer, Northwestern University

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University Feinberg School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Male or female >40 years of age
  2. Meet ACR criteria for knee OA
  3. Able and willing to provide informed consent
  4. Average weekly pain in the index knee based on daily pain assessments of ≥ 4/10 and <9/10 on an 11-point NRS scale
  5. Willing to discontinue current medications taken for OA pain
  6. For women of child-bearing potential, willing to utilize some form of birth control or abstinence during the course of the study
  7. If taking cannabinoids, have to be on a stable dose and have this maintained for the duration of the study
  8. 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
  9. Ambulatory
  10. Have a cellphone and/or access to a computer and be able to utilize the eDiary as directed
  11. Use of medications for knee OA pain on at least 4 out of 7 days per week
  12. eDiary entries on at least 4 out 7 days per week during the observation period
  13. 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:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cross-over Treatment: Initial treatment with naproxen
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
naproxen tablets
Other Names:
  • non steroidal anti inflammatory drugs (NSAID)
Drug: Placebo
lactose NF
Experimental: Cross-over Treatment: Initial treatment with placebo
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
naproxen tablets
Other Names:
  • non steroidal anti inflammatory drugs (NSAID)
Drug: Placebo
lactose NF

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Mean of one week's daily pain ratings on Numeric Pain Scale (NRS) 0-10; higher worse
Time Frame: baseline to end of 14 day treatment period
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

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Knee Injury and Osteoarthritis Outcome Score (KOOS) 0-100; higher better
Time Frame: baseline to end of 14 day treatment period
KOOS questionnaire
baseline to end of 14 day treatment period
Pain Detect Questionnaire (PDQ) 0-38; higher more neuropathic
Time Frame: baseline to end of 14 day treatment period
PDQ
baseline to end of 14 day treatment period
Positive and Negative Affect Schedule (PANAS) questionnaire 10-50; higher more positive or negative affect
Time Frame: baseline to end of 14 day treatment period
positive and negative affect
baseline to end of 14 day treatment period
Quantitative Sensory Testing (QST) 0-100; higher is greater pain
Time Frame: baseline to end of 14 day treatment period
quantitative sensory testing parameters - temporal summation
baseline to end of 14 day treatment period
Oswestry Disability Index (ODI) 0-50; higher is greater disability
Time Frame: baseline to end of 14 day treatment period
Oswestry Disability Index
baseline to end of 14 day treatment period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Northwestern University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Thomas J Schnitzer, MD, PhD, Northwestern University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 24, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 18, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 18, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 24, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 23, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 19, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • STU00215311

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings